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Article

High-Resolution Chromosome Ideogram Representation of Currently Recognized Genes for Autism Spectrum Disorders

Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, KS 66160, USA
*
Author to whom correspondence should be addressed.
These authors contributed to this work equally.
Academic Editor: William Chi-shing Cho
Int. J. Mol. Sci. 2015, 16(3), 6464-6495; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms16036464
Received: 23 January 2015 / Revised: 11 March 2015 / Accepted: 16 March 2015 / Published: 20 March 2015

Abstract

Recently, autism-related research has focused on the identification of various genes and disturbed pathways causing the genetically heterogeneous group of autism spectrum disorders (ASD). The list of autism-related genes has significantly increased due to better awareness with advances in genetic technology and expanding searchable genomic databases. We compiled a master list of known and clinically relevant autism spectrum disorder genes identified with supporting evidence from peer-reviewed medical literature sources by searching key words related to autism and genetics and from authoritative autism-related public access websites, such as the Simons Foundation Autism Research Institute autism genomic database dedicated to gene discovery and characterization. Our list consists of 792 genes arranged in alphabetical order in tabular form with gene symbols placed on high-resolution human chromosome ideograms, thereby enabling clinical and laboratory geneticists and genetic counsellors to access convenient visual images of the location and distribution of ASD genes. Meaningful correlations of the observed phenotype in patients with suspected/confirmed ASD gene(s) at the chromosome region or breakpoint band site can be made to inform diagnosis and gene-based personalized care and provide genetic counselling for families.
Keywords: high-resolution chromosome ideograms; autism; genetic evidence; autism spectrum disorders (ASD); ASD genes high-resolution chromosome ideograms; autism; genetic evidence; autism spectrum disorders (ASD); ASD genes

1. Introduction

Classical autism or autistic disorder is common, with developmental difficulties noted by three years of age. It belongs to a group of heterogeneous conditions known as autism spectrum disorders (ASDs) with significant impairments in verbal and non-verbal communication and social interactions with restricted repetitive behaviors, specifically in movements and interests [1,2,3]. Other symptoms include lack of eye contact or focus, sleep disturbances and tactile defensiveness beginning at an early age. Several validated rating scales are used at a young age to help establish the diagnosis, including the autism diagnostic observation schedule (ADOS) and the autism diagnostic interview-revised (ADI-R) supported by pertinent medical history and clinical findings [4,5,6]. ASD affects about 1% of children in the general U.S. population with a 4:1 male to female ratio, usually without congenital anomalies or growth retardation [7,8].
Autism was first used as a term by Kanner in 1943 when describing a group of children lacking the ability to establish interpersonal contact and communication [9]. About one-fourth of children with autism are diagnosed by 2–3 years of age and show regression of skills in about 30% of cases. About 60% of ASD subjects show intellectual disabilities at a young age [10,11]. When comparing the prevalence of health disorders involving the central nervous system, autism ranks higher than epilepsy (6.5 cases per 1000), brain paralysis or dementia (2.5 cases/1000 for each) and Parkinson disease (two cases per 1000); genetic factors are related to many of these disorders [12,13]. Autism also occurs more commonly than congenital malformations in the general population, but dysmorphic findings are present in about 25% of children with autism. Microcephaly is seen in about 10% of cases, but macrocephaly is documented with larger frontal and smaller occipital lobes in about 20% of children with autism. Those with autism and extreme macrocephaly are at a greater risk to have PTEN tumor suppressor gene mutations [14], while another autism-related gene (CHD8) can also lead to macrocephaly and autism [15].
Autism is due to a wide range of genetic abnormalities, as well as non-genetic causes, including the environment, environmental and gene interaction (epigenetics) and metabolic disturbances (e.g., mitochondrial dysfunction), with the recurrence risk dependent on the family history and presence or absence of dysmorphic features. Candidate genes for ASD are identified by different means, including cytogenetic abnormalities (i.e., translocations at chromosome breakpoints or deletions (e.g., the 22q11.2 deletion) indicating the location or loss of specific genes) in individuals with ASD along with overlapping linkage and functional data related to the clinical presentation, with certain chromosome regions identified by genetic linkage using DNA markers that co-inherit with the specific phenotype [16,17]. A representative example for such an occurrence is the proto-oncogene (MET) involved in pathways related to neuronal development [18] and found to be linked to the chromosome 7q31 band, where this gene is located. Decreased activity of the gene promoter was recognized when specific single nucleotide polymorphisms (SNPs) were present in this region by linkage studies. However, genetic linkage studies have received only limited success in the study of the genetics of autism. On the other hand, chromosomal microarray analysis using DNA probes disturbed across the genome can be used to detect chromosomal abnormalities at >100-times smaller than seen in high-resolution chromosome studies. Microarray studies have also become the first tier of genetic testing for this patient population and are recommended for all ASD patients [19]. Greater than 20% of studied patients with microarray analysis are found to have submicroscopic deletions or duplications in the genome containing genes that play a role in causing autism [20,21]. Identification of causative mutations is important to guide treatment selection and to manage medical co-morbidities, such as risks for seizures, developmental regression or for cancer (e.g., the PTEN gene).
Routine cytogenetic studies have shown abnormalities of chromosomes 2, 3, 4, 5, 7, 8, 11, 13, 15, 16, 17, 19, 22 and X, including deletions, duplications, translocations and inversions involving specific chromosome regions where known or candidate genes for ASD are located [22]. These studies further support the role of genetic factors in the causation of this common neurodevelopment disorder. Specifically, cytogenetic abnormalities involving the 15q11–q13 region are found in at least 1% of individuals with ASD and include CYFIP1, GABRB3 and UBE3A genes in this chromosome region [23] and most recently the 15q11.2 BP1-BP2 microdeletion (Burnside-Butler) syndrome [24]. DNA copy number changes have also shown recurrent small deletions or duplications of the chromosome 16p11.2 band using microarray analysis [25,26] and the chromosome 15q13.2–q13.3 region [27], whereas copy number changes are noted throughout the genome in individuals with ASD, indicating the presence of multiple candidate genes on every human chromosome. These copy number changes are more often of the deletion type.
For idiopathic or non-syndromic autism, the empirical risk for siblings to be similarly affected is between 2% and 8% with an average of 4% [28]. In multiplex families having two or more affected children with autism, the recurrence risk may be as high as 25%, but generally ranges from 13% [29] to 19% [30] if due to single-gene disturbances as the cause, a major focus of this illustrative review. Advances in genetic technology beyond linkage or cytogenetic analysis of affected families with ASD or other complex disorders have led to genome-wide association studies (GWAS) involving hundreds of affected and control individuals by analyzing the distribution and clustering of hundreds and thousands of SNPs that have successfully been searched for candidate genes. The first GWAS for ASD was undertaken by Lauritsen et al. in 2006 [31] using 600 DNA markers in an isolated population of affected individuals from the Faroe Islands. They found an association of the chromosome 3p25.3 band, and later, other investigators studied more subjects with larger collections of genotyped markers and found several chromosome bands and regions ascertained when specific SNPs were over-represented in the ASD subjects, including 5p14.1, 5p15 and 16p13–p21 [32,33,34,35,36,37]. The studies implicated several gene families, including the cadherin family, encoding proteins for neuronal cell adhesion, while other genes (e.g., SEMA5A) were implicated in axonal guidance with lower gene expression levels in brain specimens from individuals with ASD [33], reviewed by Holt and Monaco [17]. Since that time, several additional studies searching for clinically relevant and known genes for ASD have identified a new collection of ASD genes [38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53].
The ability to identify an increased number of SNPs with advanced genetic platforms and extensive approaches using bioinformatics have led to improved access and a more thorough analysis. This has led to comparing genotyping data from GWAS and DNA copy number variants (CNVs) with the identification of structural genetic defects, such as submicroscopic deletions or duplications of the genome, which was not possible a few years ago. Separate studies using array comparative genomic hybridization or microarray analysis to investigate those individuals with ASD continue to yield useful data in identifying candidate genes for ASD in affected individuals [20,21,54]. The yield for microarray analysis is reported to be approximately 20% for identifying deletions or duplications at sites where known or candidate ASD genes are present. The use of more advanced technology, such as next-generation sequencing (whole genome or exome) will yield additional valuable information on the location and description of lesions of genes contributing to ASD with increasing evidence for specific and recurring mutations of single genes involved with neurodevelopment and function, leading to potential therapeutic discoveries and interventions.
Autism is frequent in single-gene conditions, such as fragile X syndrome, tuberous sclerosis, Rett syndrome or neurofibromatosis, but single-gene disorders as a whole account for less than 20% of all cases; therefore, most individuals with ASD are non-syndromic. The heritability of ASD, which takes into consideration the extent of genetic factors contributing to autism, is estimated to be as high as 90% [55]; hence the relevance and continued importance of investigating the role of genetics in the causation of ASD and expanded diagnostic testing to inform and guide treatment for individuals with identifiable genetic disturbances.
A current list of clinically relevant and known candidate genes for ASD is needed for diagnostic testing and genetic counselling purposes in the clinical setting. Historically, a previous list of known or candidate genes showing an association with ASD was reported in 2011 by Holt and Monaco [17] with the placement of 175 genes on chromosome ideograms. A much greater number of validated genes are now recognized as playing a pivotal role in ASD, warranting an updated, revised summary. We will utilize high-resolution chromosome ideograms (850 band level) to plot the location of genes now recognized by searching the literature and website information as playing a documented role in ASD. In tabular form, we will list the individual gene symbol, expanded name or description and chromosome location.

2. Results and Discussion

The diagnostic approach for an individual with ASD should include a clinical genetics evaluation with interviews of parents and health caregivers for the collection and overview of historical problems, a three-generation family pedigree, recording of developmental milestones and description of atypical behaviors along with medical and surgical procedures and a current list of medications and ongoing treatments. Laboratory tests should include lead, thyroid function, lactate and pyruvate levels in order to assess metabolic and mitochondrial functions that may be impacted by an underlying genetic disturbance along with cholesterol and urine collection for organic acid levels. Brain imaging and electroencephalogram patterns should be reviewed, if available. In addition, the ADI-R and ADOS instruments are used to test the diagnosis of ASD.
To further increase the diagnostic yield in individuals with ASD presenting for genetic service, Schaefer et al. [19] proposed and utilized a three-tier approach to include a genetic work-up by a clinical geneticist with expertise in dysmorphology to identify known syndromes with or without dysmorphic features (e.g., birth marks), growth anomalies (e.g., microcephaly, macrocephaly and short stature), viral titers (e.g., rubella) and metabolic screening (urine for organic acids and mucopolysaccharides, plasma lactate and amino acid levels). DNA testing for fragile X syndrome and Rett syndrome in females and males is also available, along with chromosomal and DNA microarrays to examine structural DNA lesions in those with a sporadic form of autism and the use of SNP arrays to examine for regions of homozygosity or uniparental disomy, whereby both members of a chromosome pair come from one parent [56]. Exome sequencing is now available particularly to those affected subjects with a positive family history of autism (multiplex families), if other diagnostic tests are uninformative. PTEN gene mutation screening would be indicated in those patients with extreme macrocephaly (head size > 2 SD) [14], if not previously done, and a review of brain MRI results. Serum and urine uric acid levels and assays for adenylate succinase deficiency should be done to include biochemical genetic studies and mitochondrial genome screening and function [57] if the above testing protocols are not diagnostic. Up to one in five children with ASD show findings of mitochondrial dysfunction [57], and a detailed genetic work-up will significantly increase the yield for the diagnosis of ASD, leading to a better understanding of causation, treatment and more accurate genetic counselling for those presenting for genetic services [20,21,54].
Advances made in genetic technology and bioinformatics have led to vastly improved genetic testing options for application in the clinical setting in patients presenting for genetic services [54]. Significant discoveries have been made with the recognition of genetic defects in the causation of ASD using microarray technology and, now, next generation sequencing. This technology has flourished with a combination of DNA probes used for both copy number variation and SNPs being required to identify segmental deletions and duplications in the genome and regions of homozygosity for the determination of identical by descent for the calculation of inbreeding coefficients or consanguinity status along with uniparental disomy of individual chromosomes [56].
Next generation exome DNA sequencing and RNA sequencing allows for discoveries of disease-causing genes and regulatory sequences required for normal function. Identifying and characterizing molecular signatures for novel or disturbed gene or exon expression and disease-specific profiles and patterns with expression heat maps have led to the recognition of interconnected disturbed gene pathways in many diseases, including a growing body of genetic evidence for autism and other psychiatric or aberrant behavioral disorders [54].
The position for each known or candidate gene for ASD susceptibility is plotted on high-resolution chromosome ideograms (850 band level), as shown in Figure 1 below. We have included gene symbols and expanded names along with the chromosome band location in Table 1 for the 792 genes recognized as playing a role in ASD.
Figure 1. High-resolution human chromosome ideograms (850 band level) with the ASD gene symbol placed at the chromosomal band location. The centromere area, highlighted in black, separates the upper short “p” arm and lower long “q” arm for each chromosome. The gene symbols are arranged in alphabetical order with the expanded name and chromosome band position listed in Table 1.
Figure 1. High-resolution human chromosome ideograms (850 band level) with the ASD gene symbol placed at the chromosomal band location. The centromere area, highlighted in black, separates the upper short “p” arm and lower long “q” arm for each chromosome. The gene symbols are arranged in alphabetical order with the expanded name and chromosome band position listed in Table 1.
Ijms 16 06464 g001aIjms 16 06464 g001b
Table 1. Recognized genes for autism spectrum disorders (ASD) and their chromosome locations.
Table 1. Recognized genes for autism spectrum disorders (ASD) and their chromosome locations.
Gene SymbolGene NameLocation
ABAT4-aminobutyrate aminotransferase16p13.2
ABCA7ATP-binding cassette, sub-family A (ABC1), member 719p13.3
ABI1Abl-interactor 110p12.1
ABI2Abl-interactor 22q33.2
ABL1C-Abl oncogene 1, non-receptor tyrosine kinase9q34.12
ACY1Aminoacylase 13p21.2
ADAAdenosine deaminase20q13.12
ADAMTS18A disintegrin-like and metalloproteinase with thrombospondin type 1 motif, 1816q23.1
ADARB1Adenosine deaminase, RNA-specific, B121q22.3
ADCY5Adenylate cyclase 53q21.1
ADKAdenosine kinase10q22.2
ADNPActivity-dependent neuroprotector homeobox20q13.13
ADORA2AAdenosine A2A receptor22q11.23
ADORA3Adenosine A3 receptor1p13.2
ADRB2Adrenergic, β 2 receptor5q32
ADSLAdenylosuccinate lyase22q13.1
AFF2AF4/fragile X mental retardation 2 (FMR2) family, member 2Xq28
AFF4AF4/fragile X mental retardation 2 (FMR2) family, member 45q31.1
AGBL4ATP/GTP binding protein-like 41p33
AGMOAlkylglycerol monooxygenase7p21.1
AGTR2Angiotensin II receptor, type 2Xq23
AHI1Abelson helper integration site 16q23.3
AHRRAryl hydrocarbon receptor repressor5p15.33
AKT1v-Akt murine thymoma viral oncogene homolog 114q32.33
ALDH1A3Aldehyde dehydrogenase 1 family, member A315q26.3
ALDH5A1Aldehyde dehydrogenase 5 family, member A16p22.3
ALOX5APArachidonate 5-lipoxygenase-activating protein13q12.3
AMPD1Adenosine monophosphate deaminase 11p13.2
AMTAminomethyltransferase3p21.31
ANK2Ankyrin 24q25
ANK3Ankyrin 310q21.2
ANKRD11Ankyrin repeat domain 1116q24.3
ANXA1Annexin A19q21.13
AP1S2Adaptor-related protein complex 1, sigma 2 subunitXp22.2
APBA2Amyloid β precursor protein-binding, family A, member 215q13.1
APCAdenomatosis polyposis coli5q22.2
APH1AAPH1A γ secretase subunit1q21.2
APOBEC3DApolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3D22q13.1
APPAmyloid β precursor protein21q21.3
ARAndrogen receptorXq12
ARHGAP11BRho GTPase activating protein 11B15q13.2
ARHGAP15Rho GTPase activating protein 152q22.2
ARHGAP24Rho GTPase activating protein 244q22.1
ARHGEF6RAC/CDC42 guanine nucleotide exchange factor (GEF) 6Xq26.3
ARID1BAT rich interactive domain 1B (SWI1-like)6q25.3
ARID5AAT rich interactive domain 5A (MRF1-like)2q11.2
ARL6IP6ADP-ribosylation-like factor 6 interacting protein 62q23.3
ARNT2Aryl-hydrocarbon receptor nuclear translocator 215q25.1
ARXAristaless related homeoboxXp21.3
ASH1LAsh1 (absent, small, or homeotic)-like (Drosophila)1q22
ASMTAcetylserotonin O-methyltransferase, X-chromosomalXp22.33
ASMTAcetylserotonin O-methyltransferase, Y-chromosomalYp11.32
ASPHD1Aspartate β-hydroxylase domain containing 116p11.2
ASPMAsp (abnormal spindle) homolog, microcephaly associated1q31.3
ASS1Argininosuccinate synthetase9q34.1
ASTN2Astrotactin 29q33.1
ASXL3Additional sex combs-like 318q12.1
ATG7Autophagy related 73p25.3
ATP10AATPase, Class V, type 10A15q11.2
ATP2B2ATPase, Ca++ transporting, plasma membrane 23p25.3
ATRNL1Attractin-like 110q25.3
ATRXα thalassemia/mental retardation syndrome X-linkedXq21.1
ATXN7Ataxin 73p14.1
AUTS2Autism susceptibility candidate 27q11.22
AVPR1AArginine vasopressin receptor 1A12q14.2
AXLAXL receptor tyrosine kinase19q13.2
BAIAP2BAI1-associated protein 217q25.3
BBS4Bardet-Biedl syndrome 415q24.1
BCKDKBranched chain ketoacid dehydrogenase kinase16p11.2
BCL11AB-Cell CLL/lymphoma 11A (zinc finger protein)2p16.1
BCL2B-cell CLL/lymphoma 218q21.33
BCORL1Bc16 co-repressor-like 1Xq26.1
BDNFBrain-derived neurotrophic factor11p14.1
BIN1Bridging integrator 12q14.3
BIRC6Baculoviral IAP repeat containing 62p22.3
BRAFv-Raf murine sarcoma viral oncogene homolog B7q34
BRCA2Breast cancer 2, early onset13q13.1
BTAF1RNA polymerase II, B-TFIID transcription factor-associated, 170 kDa (Mot1 homolog, S. cerevisiae)10q23.32
BZRAP1Benzodiazepine receptor (peripheral) associated protein 117q23.2
C11ORF30Chromosome 11 open reading frame 3011q13.5
C12ORF57Chromosome 12 open reading frame 5712p13.31
C15ORF43Chromosome 15 open reading frame 4315q21.1
C3ORF58Chromosome 3 open reading frame 583q24
C4BComplement component 4B6p21.33
CA6Carbonic anhydrase VI1p36.2
CACNA1BCalcium channel, voltage-dependent, N type, α 1B subunit9q34.3
CACNA1CCalcium channel, voltage-dependent, L type, α 1C subunit12p13.33
CACNA1DCalcium channel, voltage-dependent, L type, α 1D subunit3p14.3
CACNA1FCalcium channel, voltage-dependent, α 1F subunitXp11.23
CACNA1GCalcium channel, voltage-dependent, T type, α 1G subunit17q21.33
CACNA1HCalcium channel, voltage-dependent, α 1H subunit16p13.3
CACNA1ICalcium channel, voltage-dependent, T type, α 1I subunit22q13.1
CACNA2D3Calcium channel, voltage-dependent, α 2/δ subunit 33p21.1
CACNB2Calcium channel, voltage-dependent, β 2 subunit10p12.33
CADM1Cell adhesion molecule 111q23.3
CADPS2Ca++-dependent activator protein for secretion 27q31.32
CALM1Calmodulin 1 (phosphorylase kinase, δ)14q32.11
CAMK4Calcium/calmodulin-dependent protein kinase 5q22.1
CAMSAP2Calmodulin regulated spectrin-associated protein family, member 21q32.1
CAMTA1Calmodulin binding transcription activator 11p36.31
CAPRIN1Cell cycle associated protein 111p13
CASC4Cancer susceptibility candidate 415q15.3
CBSCystathionine β-synthase21q22.3
CCAR2Cell cycle and apoptosis regulator 28p21.3
CC2D1ACoiled-coil and C2 domain-containing 1A19p13.12
CCDC19Coiled-coil domain-containing protein 191q23.2
CCDC64Coiled-coil domain-containing 6412q24.23
CD38CD38 molecule4p15.32
CD44CD44 molecule 11p13
CD163L1CD163 molecule-like 112p13.31
CD99L2CD99 molecule-like 2Xq28
CDC42BPBCDC42 binding protein kinase β (DMPK-like)14q32.32
CDH10Cadherin 10, type 2 5p14.2
CDH22Cadherin-like 2220q13.1
CDH8Cadherin 8, type 216q22.1
CDH9Cadherin 9, type 2 5p14.1
CDH11Cadherin 11, type 216q21
CDKL5Cyclin-dependent kinase-like 5Xp22.13
CDKN1BCyclin-dependent kinase inhibitor 1B 12p13.1
CECR2Cat eye syndrome chromosome region, candidate 222q11.21
CELF4CUGBP, Elav-like family, member 418q12.2
CELF6CUGBP, Elav-like family, member 615q23
CENTG2Centaurin γ-22q37.2
CEP170RCentrosomal protein 170B14q32.33
CEP290Centrosomal protein 290 kDa12q21.32
CEP41Centrosomal protein 41 kDa7q32.2
CHD1Chromodomain helicase DNA binding protein 15q21.1
CHD2Chromodomain helicase DNA binding protein 215q26.1
CHD3Chromodomain helicase DNA binding protein 317p13.1
CHD7Chromodomain helicase DNA binding protein 78q12.2
CHD8Chromodomain helicase DNA binding protein 814q11.2
CHRM3Cholinergic receptor, muscarinic 31q43
CHRNA7Cholinergic receptor, neuronal nicotinic, α 715q13.3
CHRNB3Cholinergic receptor, neuronal nicotinic, β 3 8p11.21
CHST5Carbohydrate sulfotransferase 516q22.3
CIB2Calcium and integrin binding family member 215q25.1
CKAP5Cytoskeleton associated protein 511p11.2
CLCNKBChloride channel voltage-sensitive kidney, B1p36.13
CLSTN3Calsyntenin 312p13.31
CLTCL1Clathrin, heavy chain-like 122q11.21
CMIPc-MAF inducing protein16q23.2
CNR1Cannabinoid receptor 16q15
CNR2Cannabinoid receptor 21p36.11
CNTN3Contactin 33p12.3
CNTN4Contactin 43p26.3
CNTN5Contactin 511q22.1
CNTN6Contactin 63p26.3
CNTNAP2Contactin associated protein-like 27q35
CNTNAP3Contactin associated protein-like 39p13.1
CNTNAP4Contactin associated protein-like 416q23.1
CNTNAP5Contactin associated protein-like 52q14.3
COL7A1Collagen, type VII, α 13p21.31
COPS2Thyroid hormone receptor interactor 1515q21.1
CREBBPCREB binding protein16p13.3
CSMD1Cytoskeleton associated protein 511p11.2
CSNK1DCasein kinase 1, δ17q25
CSTF2TCleavage stimulation factor, 3' pre-RNA, subunit 2, 64 kDa, tau10q21.1
CTCFCCCTC-binding factor16q22.1
CTNNA3Catenin (cadherin-associated protein), α 310q21.3
CTNNB1Catenin (cadherin-associated protein), β 1, 88 kDa3p22.1
CTSBCathepsin B8p23.1
CTTNBP2Cortactin binding protein 27q31.31
CTU2Cytosolic thiouridylase subunit 2 homolog (S. pombe)16q24.3
CUEDC2CUE domain containing 210q24.32
CUL5Cullin 511q22.3
CUL3Cullin 32q36.2
CX3CR1Chemokine (C-X3-C motif) receptor 13p22.2
CXCR3Chemokine, CXC motif, receptor 3Xq13.1
CYFIP1Cytoplasmic FMRP interacting protein 115q11.2
CYP11B1Cytochrome P450, subfamily XIB, polypeptide 18q24.3
DAB1Disabled homolog 11p32.2
DAG1Dystroglycan 1 (dystrophin-associated glycoprotein 1)3p21.31
DAGLADiacylglycerol lipase, α11q12.2
DAPK1Death-associated protein kinase 19q21.33
DAPP1Dual adaptor of phosphotyrosine and 3-phosphoinositides 14q23
DCAF13DDB1 and CUL4 associated factor 138q22.3
DCAKDDephospho-CoA kinase domain-containing protein17q21.31
DCTN5Dynactin 516p12.2
DCUN1D1DCN1, domain containing protein 1 3q27.1
DCXDoublecortinXq23
DDCDOPA decarboxylase 7p12.1
DDX11DEAD (Asp-Glu-Ala-Asp)/H box 1112p11.21
DDX53DEAD (Asp-Glu-Ala-Asp) box polypeptide 53Xp22.11
DEAF1DEAF1 transcription factor11p15.5
DEPDC5DEP domain containing 3 protein 522q12.2
DHCR77-dehydrocholesterol reductase11q13.4
DHX9DEAH (Asp-Glu-Ala-His) box helicase 91q25.3
DIAPH3Diaphanous, Drosophila, homolog 313q21.2
DIP2ADIP2 disco-interacting protein 2 homolog A (Drosophila)21q22.3
DISC1Disrupted in schizophrenia 11q42.2
DLG4Discs, large, Drosophila, homolog 4 17p13.1
DLGAP2Discs, large- associated protein 28p23.3
DLGAP3Discs, large- associated protein 31p34.3
DLL1δ-like 1 (Drosophila)6q27
DLX1Distal-less homeobox 12q31.1
DLX2Distal-less homeobox 22q31.1
DLX6Distal-less homeobox 67q21.3
DMDDystrophin Xp21.1
DMPKDystrophia myotonica-protein kinase19q13.32
DNAJC19DNAJ Hsp40 homolog, subfamily C, member 193q26.33
DNERδ- and notch-like epidermal growth factor-related receptor2q36.3
DNM1LDynamin 1-like12p11.21
DNMT3ADNA (cytosine-5)-methyltransferase 3 α2p23.3
DOCK4Dedicator of cytokinesis 47q31.1
DOCK10Dedicator of cytokinesis 102q36.2
DOLKDolichol kinase9q34.1
DPP10Dipeptidyl peptidase 102q14.1
DPP6Dipeptidyl peptidase 67q36.2
DPYDDihydropyrimidine dehydrogenase1p21.3
DRD1Dopamine receptor D15q35.2
DRD2Dopamine receptor D211q23.2
DRD3Dopamine receptor D33q13.31
DSCAMDown syndrome cell adhesion molecule21q22.2
DSTDystonin6p12.1
DUSP22Dual specificity phosphatase 226p25.3
DYDC1DPY30 domain containing 110q23.1
DYDC2DPY30 domain containing 210q23.1
DYRK1ADual-specificity tyrosine-phosphorylation-regulated kinase 1A21q22.13
EEF1A2Eukaryotic translation elongation factor 1 α 220q13.33
EFR3AEFR3 homolog A (S. cerevisiae)8q24.22
EGR2Early growth response 2 10q21.3
EHMT1Euchromatic histone methyltransferase 19q34.3
EIF2S3Eukaryotic translation initiation factor 2, subunit 3 γXp22.11
EIF4EEukaryotic translation initiation factor 4E4q23
EIF4EBP2Eukaryotic translation initiation factor 4E binding protein 210q22.1
EML1Echinoderm microtubule associated protein like 114q32.2
EN2Engrailed 27q36.3
EP300E1A binding protein p30022q13.2
EP400E1A binding protein p40012q24.33
EPC2Enhancer of polycomb, Drosophila homolog of 2 2q23.1
EPHA6Ephrin receptor A63q11.2
EPHB2Ephrin receptor B21p36.12
EPHB6Ephrin receptor B67q34
EPS8Epidermal growth factor receptor pathway substrate 812p12.3
ERBB4v-ERB-A avian erythroblastic leukemia viral oncogene homolog 4 2q34
ERGv-ETS avian erythroblastosis virus E26 oncogene homolog 21q22.2
ESR1Estrogen receptor 16q25.1
ESR2Estrogen receptor 2 14q23.2
ESRRBEstrogen-related receptor β14q24.3
ETFBElectron-transfer-flavoprotein, β polypeptide19q13.41
ETV1Ets variant 17p21.2
EXOC6BExocyst complex component 6B2p13.2
EXT1Exostosin 18q24.11
F13A1Factor XIII, A1 subunit6p25.1
FABP3Fatty acid binding protein 3, muscle and heart (mammary-derived growth inhibitor)1p35.2
FABP5Fatty acid binding protein 5 8q21.13
FABP7Fatty acid binding protein 76q22.31
FAM135BFamily with sequence similarity 135, member B8q24.23
FAN1FANCD2/FANCI-associated nuclease 115q13.2
FAT1FAT tumor suppressor, Drosophila homolog of, 1 4q35.2
FAT3FAT tumor suppressor, Drosophila homolog of , 311q14.3
FBXO15F-box protein 1518q22.3
FBXO33F-box protein 3314q21.1
FBXO40F-box protein 403q13.33
FBXW7F-box and WD repeat domain containing 7, E3 ubiquitin protein4q31.3
FERFPS/FES related tyrosine kinase5q21.3
FEZF2FEZ family zinc finger 23p14.2
FGAFibrinogen, A α polypeptide4q31.3
FGD1FYVE, Rho GEF and PH domain containing 1Xp11.22
FGFBP3Fibroblast growth factor binding protein 310q23.32
FHITFragile histidine triad3p14.2
FLT1c-FMS-related tyrosine kinase 1 13q12.3
FMR1Fragile X mental retardation 1 (FMR1)Xq27.3
FOLH1Folate hydrolase 111p11.2
FOXG1Forkhead box G114q12
FOXP1Forkhead box P13p13
FOXP2Forkhead box P27q31.1
FRKFYN-related kinase6q22.1
FRMPD4FERM and PDZ domain containing protein 4Xp22.2
GABRA1γ-aminobutyric acid A receptor, α 15q34
GABRA3γ-aminobutyric acid receptor, α 3Xq28
GABRA4γ-aminobutyric acid receptor, α 44p12
GABRB1γ-aminobutyric acid receptor, β 14p12
GABRB3γ-aminobutyric acid receptor, β 315q12
GABRQγ-aminobutyric acid receptor, θXq28
GAD1Glutamate decarboxylase 1 (brain, 67 kDa)2q31.1
GALNT13UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyl-transferase 13 2q23.3
GALNT14UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyl-transferase 14 2p23.1
GANGigaxonin16q24.1
GAP43Growth associated protein 433q13.31
GAS2Growth arrest-specific 211p14.3
GATMGlycine amidinotransferase (l-arginine:glycine amidinotransferase)15q21.1
GDI1GDP dissociation inhibitor 1Xq28
GIGYF1GRB10 interacting GYF protein 17q22.1
GLO1Glyoxalase I6p21.2
GLRA2Glycine receptor, α 2 subunitXp22.2
GNA14Guanine nucleotide-binding protein, α 149q21.2
GNASGuanine nucleotide-binding protein, α-stimulating activity polypeptide I complex locus20q13.32
GNB1LGuanine nucleotide-binding protein, β 1-like22q11.21
GPC6Glypican 613q31.3
GPD2Glycerol-3-phosphate dehydrogenase 2 2q24.1
GPHNGephyrin14q23.3
GPR139G protein-coupled receptor 13916p12.3
GPR37G protein-coupled receptor 37 7q31.33
GPRASP2G protein-coupled receptor associated sorting protein 2Xq22.1
GPX1Glutathione peroxidase 13p21.31
GRID1Glutamate receptor, ionotropic, δ 110q23.2
GRID2Glutamate receptor, ionotropic, δ 24q22.1
GRIK2Glutamate receptor, ionotropic, kainate 26q16.3
GRIN1Glutamate receptor, ionotropic, N-methyl d-aspartate 19q34.3
GRIN2AGlutamate receptor, ionotropic, N-methyl d-aspartate 2A16p13.2
GRIN2BGlutamate receptor, ionotropic, N-methyl d-aspartate 2B12p13.1
GRINL1AGRINL1A complex locus 115q21.3
GRIP1Glutamate receptor interacting protein 112q14.3
GRM1Glutamate receptor, metabotropic 16q24.3
GRM4Glutamate receptor, metabotropic 46p21.31
GRM5Glutamate receptor, metabotropic 511q14.3
GRM8Glutamate receptor, metabotropic 87q31.33
GRPRGastrin-releasing peptide receptorXp22.2
GSE1Gse1 coiled-coil protein16q24.1
GSK3BGlycogen synthase kinase 3 β3q13.33
GSNGelsolin9q33.2
GSTM1Glutathione S-transferase M11p13.3
GTF2IGeneral transcription factor III7q11.23
GTF2IRD1GTF2I repeat domain containing 17q11.23
GTF3C1General transcription factor IIIC, polypeptide 1, α16p12.1
GUCY1A2Guanylate cyclase 1, soluble, α 211q22.3
HCAR1Hydroxycarboxylic acid receptor 1/G protein-coupled receptor 8112q24.31
HCFC1Host cell factor C1 Xq28
HCN1Hyperpolarization activated cyclic nucleotide-gated potassium channel 15p12
HDAC4Histone deacetylase 42q37.3
HDAC6Histone deacetylase 6Xp11.23
HDAC9Histone deacetylase 97p21.1
HDLBPHigh density lipoprotein binding protein2q37.3
HEPACAMHepatic and glial cell adhesion molecule11q24.2
HERC2HECT domain and RCC1-like domain 215q13.1
HLA-AMajor histocompatibility complex, class I, A6p22.1
HLA-DRB1Major histocompatibility complex, class II, DR β 16p21.32
HMGN1High mobility group nucleosome binding domain 121q22.2
HNRNPFHeterogeneous nuclear ribonucleoprotein F10q11.21
HNRNPH2Heterogeneous nuclear ribonucleoprotein H2 Xq22.1
HNRNPUL1Heterogeneous nuclear ribonucleoprotein U-like 119q13.2
HOMER1Homer, Drosophila, homolog 1 of 15q14.1
HOXA1Homeobox A17p15.3
HOXB1Homeobox B117q21.32
HRASv-HA-RAS Harvey rat sarcoma viral oncogene homolog11p15.5
HS3ST5Heparan sulfate 3-O-sulfotransferase 56q22.31
HSD11B111-β-hydroxysteroid dehydrogenase type 11q32.2
HSPA4Heat shock 70 kDa protein 45q31.1
HTR1B5-hydroxytryptamine receptor 1B6q14.1
HTR2A5-hydroxytryptamine receptor 2A13q14.2
HTR3A5-hydroxytryptamine receptor 3A11q23.2
HTR3C5-hydroxytryptamine receptor 3, family member C3q27.1
HTR75-hydroxytryptamine receptor 7 10q23.31
HUWE1HECT, UBA and WWE domain containing 1, E3 ubiquitin protein ligaseXp11.22
HYDINHydrocephalus-inducing, mouse, homolog of 16q22.2
ICA1Islet cell autoantigen 17p21.3
IL1R2Interleukin 1 receptor, type II2q11.2
IL1RAPL1Interleukin 1 receptor accessory protein-like 1Xp21.3
IL1RAPL2Interleukin 1 receptor accessory protein-like 2Xq22.3
IMMP2LInner mitochondrial membrane peptidase, subunit 2, S. cerevisiae, homolog of7q31.1
IMPDH2Inosine-5-prime monophosphate dehydrogenase 23p21.31
INADLInactivation no after-potential D-like 1p31.3
INPP1Inositol polyphosphate-1-phosphatase2q32.2
INPP5Inositol polyphosphate-5-phosphatase17p13.3
IQSEC2IQ motif and Sec7 domain 2Xp11.22
ITGA4Integrin, α 4 2q31.3
ITGB3Integrin, β 3 17q21.32
ITGB7Integrin, β 712q13.13
ITKIL20 inducible t-cell kinase5q33.3
JARID2Jumonji, AT rich interactive domain 26p22.3
JMJD1CJumonji domain containing 1C10q21.3
JUPJunction plakoglobin17q21.2
KAL1Kallmann syndrome interval 1Xp22.31
KANK1KN motif and ankyrin repeat domains 19p24.3
KATNAL2Katanin p60 subunit A-like 218q21.1
KCND2Potassium voltage-gated channel, Shal-related subfamily, member 27q31.31
KCNJ2Potassium inwardly-rectifying channel, subfamily J, member 217q24.3
KCNJ10Potassium inwardly-rectifying channel, subfamily J, member 101q23.2
KCNMA1Potassium large conductance calcium-activated channel, subfamily M, α member 110q22.3
KCNQ2Potassium voltage-gated channel, KQT-like subfamily, member 220q13.3
KCNQ3Potassium voltage-gated channel, KQT-like subfamily, member 38q24.22
KCNT1Potassium channel, subfamily T, member 19q34.3
KCTD13Potassium channel tetramerization domain containing protein 1316p11.2
KDM5ALysine (K)-specific demethylase 5A12p13.33
KDM5BLysine (K)-specific demethylase 5B1q32.1
KDM5CLysine (K)-specific demethylase 5CXp11.22
KDM6BLysine (K)-specific demethylase 6B17p13.1
KHDRBS2KH domain containing, RNA binding, signal transduction associated protein 26q11.1
KIAA1217Sickle tail protein homolog10p12.31
KIAA1586KIAA15866p12.1
KIAA2022KIAA2022Xq13.3
KIF5CKinesin family member 5C2q23.1
KIRREL3Kin of IRRE like 311q24.2
KITv-KIT Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog4q12
KLC2Kinesin light chain 211q13.2
KMOKynurenine 3-monooxygenase 1q43
KMT2ALysine (K)-specific methyltransferase 2A11q23.3
KMT2CLysine (K)-specific methyltransferase 2C7q36.1
KMT2ELysine (K)-specific methyltransferase 2E7q22.3
KPTNKaptin (actin binding protein)19q13.32
LAMA1Laminin, α 118p11.23
LAMB1Laminin, β 17q31.1
LAMC3Laminin, γ 39q34.1
LEPLeptin7q32.1
LIN7BLin-7 homolog B (C. elegans)19q13.33
LMNALamin A/C1q22
LMX1BLIM homeobox transcription factor 1, β9q33.3
LRFN5Leucine-rich repeats and fibronectin type III domain containing 514q21.1
LRGUKLeucine-rich repeats and guanylate kinase domain containing7q33
LRP2Low density lipoprotein receptor-related protein 22q31.1
LRPPRCLeucine-rich PPR motif containing protein 2p21
LRRC1Leucine-rich repeat-containing protein 16p12.1
LRRC4Leucine-rich repeat-containing protein 47q32.1
LRRC7Leucine-rich repeat-containing protein 71p31.1
LZTS2Leucine zipper, putative tumor suppressor 210q24.31
MACROD2Macro domain containing 220p12.1
MAGED1Melanoma antigen family D, 1Xp11.22
MAGEL2MAGE-like 215q11.2
MAOAMonoamine oxidase AXp11.3
MAOBMonoamine oxidase BXp11.23
MAP1AMicrotubule-associated protein 1A15q15.3
MAP2Microtubule-associated protein (MAP) 22q34
MAP4Microtubule-associated protein (MAP) 43p21.31
MAPK1Mitogen-activated protein kinase 122q11.22
MAPK3Mitogen-activated protein kinase 316p11.2
MAPK8IP2Mitogen-activated protein kinase 8 interacting protein 222q13.33
MARK1MAP/microtubule affinity-regulating kinase 11q41
MBD1Methyl-CpG binding domain protein 118q21.1
MBD3Methyl-CpG binding domain protein 319p13.3
MBD4Methyl-CpG binding domain protein 43q21.3
MBD5Methyl-CpG binding domain protein 52q23.1
MBD6Methyl-CpG binding domain protein 612q13.2
MC4RMelanocortin 4 receptor18q21.32
MCCMutated in colorectal cancers5q22.2
MCPH1Microcephalin 18p23.1
MDGA2Mephrin, A5 antigen, protein tyrosine phosphatase mu (MAM) domain containing glycosylphosphatidylinositol anchor 214q21.3
MDM2MDM2 oncogene, E3 ubiquitin protein ligase12q15
MECP2Methyl CpG binding protein 2Xq28
MED12Mediator complex subunit 12Xq13.1
MED13LMediator complex subunit 13-like12q24.21
MEF2CMADS box transcription myocyte enhancer factor 2, polypeptide C5q14.3
METMet proto-oncogene 7q31.2
MIB1Mind bomb E3 ubiquitin protein ligase 118q11.2
MICAL3Microtubule-associated monooxygenase, calponin and lim domains-containing, 322q11.21
MICALCLMICAL C-terminus-like protein11p15.3
MKL2Myocardin-like 216p13.12
MOV10Moloney leukemia virus 10, mouse, homolog of1p13.2
MSNMoesinXq12
MSNP1ASMoesin pseudogene 1 antisense5p14.1
MSR1Macrophage scavenger receptor 8p22
MTF1Metal-regulatory transcription factor 11p34.3
MTHFR5-10-methylene-tetrahydrofolate reductase 1p36.22
MTR5-methyltetrahydrofolate-homocysteine S-methyltransferase1q43
MTX2Metaxin 22q31.1
MXRA5Matrix-remodelling associated 5Xp22.2
MYH4Myosin, heavy chain 4, skeletal muscle17p13.1
MYH10Myosin, heavy chain 10, non-muscle17p13.1
MYO16Myosin XVI13q33.3
MYO1AMyosin IA12q13.3
MYO9BMyosin IXB19p13.11
MYT1LMyelin transcription factor 1-like2p25.3
NAA15N(α)-acetyltransferase 15, NatA auxiliary subunit4q31.1
NASPNuclear autoantigenic sperm protein (histone-binding)1p34.1
NAV1Neuron navigator 11q32.1
NBEANeurobeachin13q13.3
NCKAP1NCK-associated protein 12q32.1
NCKAP5NCK-associated protein 52q21.2
NCKAP5LNCK-associated protein 5-like12q13.12
NCOR1Nuclear receptor corepressor 117p11.2
NDNL2Necdin-like gene 215q13.1
NDUFA5NADH-ubiquinone oxidoreductase 1 α subcomplex, 57q31.32
NEFLNeurofilament protein, light polypeptide8p21.2
NELL1NEL-like 1 11p15.1
NF1Neurofibromin 1 17q11.2
NFIANuclear factor I/A1p31.3
NIPA1Non imprinted gene in Prader-Willi/Angelman syndrome chromosomal region 115q11.2
NIPA2Non imprinted gene in Prader-Willi/Angelman syndrome chromosomal region 215q11.2
NIPBLNipped-B-like 5p13.2
NLGN1Neuroligin 13q26.31
NLGN2Neuroligin 217p13.1
NLGN3Neuroligin 3Xq13.1
NLGN4XNeuroligin 4, X-linkedXp22.31
NLGN4YNeuroligin 4, Y-linkedYq11.221
NOS1APNitric oxide synthase 1 (neuronal) adaptor protein1q23.3
NOS2ANitric oxide synthase 2A 17q11.2
NOTCH3Notch 319p13.12
NPAS2Neuronal PAS domain protein 22q11.2
NR0B1Nuclear receptor subfamily 0, group B, member 1Xp21.2
NR3C2Nuclear receptor subfamily 3, group C, member 24q31.23
NR4A1Nuclear receptor subfamily 4, group A, member 112q13.13
NRCAMNeuronal cell adhesion molecule7q31.1
NRG1Neuregulin 18p12
NRP2Neuropilin 22q33.3
NRXN1Neurexin I2p16.3
NRXN2Neurexin II11q13.1
NRXN3Neurexin III14q24.3
NSD1Nuclear receptor-binding Sa-var, enhancer of zeste, and trithorax domain protein 15q35.3
NTNG1Netrin G11p13.3
NTRK1Neurotrophic tyrosine kinase, receptor, type 11q23.1
NTRK3Neurotrophic tyrosine kinase, receptor, type 315q25.3
NXF5Nuclear RNA export factor 5Xq22.1
NXPH1Neurexophilin 17p21.3
ODF3L2Outer dense fiber of sperm tails 3-like 219p13.3
OGTO-linked N-acetylglucosamine transferaseXq13.1
OPHN1Oligophrenin 1Xq12
OPRM1Opioid receptor, mu 16q25.2
OR1C1Olfactory receptor, family 1, subfamily C, member 11q44
OTX1Orthodenticle Drosophila, homolog of 2p15
OXTROxytocin receptor3p25.3
P2RX4Purinergic receptor P2X, ligand-gated ion channel, 412q24.31
PAFAH1B1Platelet-activating factor acetylhydrolase 1B, regulatory subunit 117p13.3
PAHPhenylalanine hydroxylase12q23.2
PARD3BPAR-3 family cell polarity regulator β2q33.3
PARK2Parkin6q26
PAX5Paired box 59p13.2
PBRM1Polybromo 13p21.1
PCDH10Protocadherin 104q28.3
PCDH15Protocadherin 1510q21.1
PCDH19Protocadherin 19Xq22.1
PCDH8Protocadherin 813q14.3
PCDH9Protocadherin 913q21.32
PCDHA1Protocadherin α 15q31.3
PCDHA10Protocadherin α 105q31.3
PCDHA11Protocadherin α 115q31.3
PCDHA12Protocadherin α 125q31.3
PCDHA13Protocadherin α 135q31.3
PCDHA2Protocadherin α 25q31.3
PCDHA3Protocadherin α 35q31.3
PCDHA4Protocadherin α 45q31.3
PCDHA5Protocadherin α 55q31.3
PCDHA6Protocadherin α 65q31.3
PCDHA7Protocadherin α 75q31.3
PCDHA8Protocadherin α 85q31.3
PCDHA9Protocadherin α 95q31.3
PCDHAC1Protocadherin α subfamily C, member 15q31.3
PCDHAC2Protocadherin α subfamily C, member 25q31.3
PCDHGA11Protocadherin γ subfamily A, member 115q31.3
PDE1CPhosphodiesterase 1C7p14.3
PDE4APhosphodiesterase 4A, cAMP-specific19p13.2
PDE4BPhosphodiesterase 4B, cAMP-specific1p31.3
PDZD4PDZ domain containing 4Xq28
PECRPeroxisomal trans-2-enoyl-CoA reductase2q35
PER1Period, Drosophila, homolog of 17p13.1
PEX7Peroxisomal biogenesis factor 76q23.3
PGDPhosphogluconate dehydrogenase1p36.22
PHF2PHD finger protein 29q22.31
PHF8PHD finger protein 8Xp11.22
PIAS1Protein inhibitor of activated STAT, 115q23
PIK3CGPhosphatidylinositol-3-kinase, catalytic, γ 7q22.3
PIK3R2Phosphatidylinositol-3-kinase, regulatory subunit 2 19q13.11
PINX1PIN2 interacting protein 18p23.1
PITX1Paired-like homeodomain transcription factor 15q31.1
PLAURPlasminogen activator receptor, urokinase-type19q13.31
PLCB1Phospholipase C, β 1 20p12.3
PLCD1Phospholipase C, δ 13p22.2
PLNPhospholamban6q22.31
PLXNA4Plexin A47q32.3
POGZPOGO transposable element with ZNF domain1q21.3
POLR2LPolymerase (RNA) II (DNA directed) polypeptide L, 7.6 kDa11p15.5
POMGNT1Protein O-mannose β-1, 2-N-acetylglucosaminyl-transferase1p34.1
PON1Paraoxonase 17q21.3
POT1Protection of telomeres 1 7q31.33
PPFIA1Protein tyrosine phosphatase, receptor type, F polypeptide, interacting protein, α 111q13.3
PPP1CBProtein phosphatase 1, catalytic subunit, β isozyme2p23.2
PPP1R1BProtein phosphatase 1, regulatory (inhibitor) subunit 1B17q12
PPP1R3FProtein phosphatase 1, regulatory (inhibitor) subunit 3FXp11.23
PRODHProline dehydrogenase (oxidase) 122q11.21
PRICKLE1Prickle, Drosophila, homolog of, 1 12q12
PRICKLE2Prickle, Drosophila, homolog of, 2 3p14.1
PRKCBProtein kinase C, β16p12.2
PRKCB1Protein kinase C, β-116p12.2
PRKD1Protein kinase D114q12
PRDX1Peroxiredoxin 11p34.1
PRSS38Protease, serine, 381q42.13
PRUNE2Prune, Drosophila, homolog of, 2 9q21.2
PSD3Pleckstrin and Sec7 domains-containing protein 38p22
PSEN1Presenilin 114q24.2
PSMD10Proteasome 26S subunit, non-ATPase, 10Xq22.3
PTCHD1Patched domain containing protein 1Xp22.11
PTENPhosphatase and tensin homolog 10q23.31
PTGER3Prostaglandin E receptor 3, EP3 subtype1p31.1
PTGS2Prostaglandin-endoperoxide synthase 21q31.1
PTPN11Protein tyrosine phosphatase, non-receptor type 1112q24.13
PTPRBProtein tyrosine phosphatase, receptor type, B12q15
PTPRCProtein tyrosine phosphatase, receptor type, C1q31.3
PTPRMProtein tyrosine phosphatase, receptor type, M18p11.23
PTPRTProtein tyrosine phosphatase, receptor type, T20q13.11
PXDNPeroxidasin, Drosophila homolog of 2p25.3
RAB11FIP5RAB11 family-interacting protein 52p13.2
RAB19RAB19, member RAS oncogene family7q34
RAB39BRAS-associated protein RAB39BXq28
RAI1Retinoic acid induced gene 117p11.2
RAPGEF4Rap guanine nucleotide exchange factor2q31.1
RASD1RAS protein, dexamethasone-induced, 117p11.2
RASSF1RAS association (ralGDS/AF-6) domain family member 13p21.31
RASSF5RAS association domain family protein 51q32.1
RB1CC1RB1-inducible coiled-coil 18q11.23
RBFOX1RNA binding protein FOX-1, C. elegans, homolog of, 116p13.3
RBM8ARNA binding motif protein 8A1q21.1
RBMS3RNA binding motif protein, single stranded interacting, 33p24.1
REEP3Receptor expression-enhancing protein 310q21.3
RELNReelin7q22.1
RERERE-repeats encoding gene1p36.23
RFWD2Ring finger and WD repeat domains-containing protein 21q25.2
RGS7Regulator of G protein signaling 71q43
RHOXF1RHOX homeobox family, member 1Xq24
RIC8ARIC8 guanine nucleotide exchange factor A11p15.5
RIMS1Regulating synaptic membrane exocytosis 16q13
RIMS3Protein regulating synaptic membrane exocytosis 31p34.2
RNPS1RNA binding protein S116p13.3
ROBO1Roundabout, Drosophila, homolog of, 1 3p12.2
ROBO2Roundabout, Drosophila, homolog of, 2 3p12.3
RORARAR-related orphan receptor A15q22.2
RPL10Ribosomal protein L10Xq28
RPP25Ribonuclease P/MRP 25 kDa subunit15q24.2
RPS6KA1Ribosomal protein S6 kinase, 90 kDa, polypeptide 11p36.11
RPS6KA2Ribosomal protein S6 kinase, 90 kDa, polypeptide 26q27
RPS6KA3Ribosomal protein S6 kinase, 90 kDa, polypeptide 3Xp22.12
RUVBL1RuvB-E. coli, homolog-like 13q21.3
SAE1SUMO1 activating enzyme, subunit 119q13.32
SATB2Special AT-rich sequence-binding protein 22q33.1
SBF1SET binding factor 122q13.33
SCFD2Sec1 family domain containing 24q12
SCN1ASodium channel, neuronal, type I, α subunit2q24.3
SCN2ASodium channel, voltage-gated, type II, α subunit2q24.3
SCN7ASodium channel, voltage-gated, type VII, α subunit2q24.3
SCN8ASodium channel, voltage-gated, type VIII, α subunit12q13.13
SDC2Syndecan 2 8q22.1
SDK1Sidekick cell adhesion molecule 17p22.2
SEMA3FSema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3F3p21.31
SEMA5ASemaphorin 5A5p15.31
SERPINE1Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 17q22.1
SETBP1SET binding protein 118q12.3
SETD2SET domain containing protein 23p21.31
SETD5SET domain containing protein 53p25.3
SETDB1SET domain, bifurcated, 11q21.3
SETDB2SET domain, bifurcated, 213q14.2
SEZ6L2Seizure related 6 homolog (mouse)-like 216p11.2
SF1Splicing factor 111q13.1
SFPQSplicing factor proline/glutamine-rich1p34.3
SFTPDSurfactant, pulmonary-associated protein D10q22.3
SGSHN-sulfoglucosamine sulfohydrolase17q25.3
SGSM3Small G protein signaling modulator 322q13.1
SH3KBP1SH3-domain kinase binding protein 1Xp22.12
SHANK1SH3 and multiple ankyrin repeat domains 119q13.3
SHANK2SH3 and multiple ankyrin repeat domains 211q13.4
SHANK3SH3 and multiple ankyrin repeat domains 322q13.33
SLC16A3Solute carrier family 16 (monocarboxylic acid transporter), member 317q25
SLC16A7Solute carrier family 16 (monocarboxylic acid transporter), member 712q14.1
SLC1A1Solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter), member 19p24.2
SLC22A15Solute carrier family 22, (organic cation transporter), member 151p13.1
SLC24A2Solute carrier family 24 (sodium/potassium/calcium exchanger), member 29p22.1
SLC25A12Solute carrier family 25 (mitochondrial carrier, Aralar), member 122q31.1
SLC25A14Solute carrier family 25 (mitochondrial carrier, brain), member 14Xq26.1
SLC25A24Solute carrier family 25 (mitochondrial carrier, phosphate carrier), member 241p13.3
SLC25A27Solute carrier family 25, member 276p12.3
SLC29A4Solute carrier family 29 (equilibrative nucleoside transporter), member 47p22.1
SLC30A5Solute carrier family 30 (zinc transporter), member 55q13.1
SLC35A3Solute carrier family 35 (UDP-N-acetylglucosamine transporter), member 31p21.2
SLC38A10Solute carrier family 38, member 1017q25.3
SLC39A11Solute carrier family 39 (metal ion transporter), member 1117q21.31
SLC4A10Solute carrier family 4 (sodium bicarbonate transporter-like), member 102q24.2
SLC6A1Solute carrier family 6 (neurotransmitter transporter), member 13p25.3
SLC6A3Solute carrier family 6 (neurotransmitter transporter, dopamine), member 35p15.33
SLC6A4Solute carrier family 6 (neurotransmitter transporter, serotonin), member 417q11.2
SLC6A8Solute carrier family 6 (neurotransmitter transporter, creatine), member 8Xq28
SLC9A6Solute carrier family 9 (sodium/hydrogen exchanger), member 6Xq26.3
SLC9A9Solute carrier family 9 (sodium/hydrogen exchanger), member 93q24
SLCO1B1Solute carrier organic anion transporter family, member 1B112p12.2
SLCO1B3Solute carrier organic anion transporter family, member 1B312p12.2
SLIT3Slit, Drosophila, homolog of, 35q35.1
SLITRK5SLIT and NTRK-like family, member 513q31.2
SLKSTE20-like kinase10q24.33
SMAD2SMAD family member 218q21.1
SMARCC2SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily C, member 212q13.2
SMG6SMG 6, C. elegans, homolog of 17p13.3
SND1EBNA2 coactivator p1007q32.1
SNRPNSmall nuclear ribonucleoprotein polypeptide N15q11.2
SNTG2Syntrophin, γ 22p25.3
SNX19Sorting nexin 1911q25
SNX5Sorting nexin 520p11.23
SOD1Superoxide dismutase 1, soluble21q22.11
SOS1Son of sevenless (SOS), Drosophila, homolog 12p22.1
SOX5SRY (sex determining region Y)-box 512p12.1
SOX7SRY (sex determining region Y)-box 78p23.1
SPASTSpastin2p22.3
SRD5A2Steroid-5-α-reductase, 2 2p23.1
ST7Suppressor of tumorigenicity 77q31.2
ST8SIA2ST8 α-N-acetyl-neuraminide α-2,8-sialyltransferase 215q26.1
STK39Serine/threonine protein kinase 39 2q24.3
STX6Syntaxin 61q25.3
STX1ASyntaxin 1A 7q11.23
STXBP1Syntaxin-binding protein 19q34.1
STXBP5Syntaxin-binding protein 5 6q24.3
STXBP5LSyntaxin-binding protein 5-like3q13.33
SUCLG2Succinate-CoA ligase, GDP-forming, β subunit3p14.1
SUV420H1Suppressor of variegation 4–20, Drosophila, homolog of, 111q13.2
SYAP1Synapse associated protein 1Xp22.2
SYN1Synapsin 1Xp11.23
SYN2Synapsin II3p25.2
SYN3Synapsin III22q12.3
SYNE1Spectrin repeat containing nuclear envelope 16q25.2
SYNGAP1Synaptic RAS-GTPase-activating protein 16p21.32
SYT17Synaptotagmin XVII16p12.3
SYT3Synaptotagmin III19q13.33
TAF1CTATA box-binding protein-associated factor 1C16q24.1
TAF1LTATA box-binding protein-associated factor 1-like9p21.1
TAS2R1Taste receptor, type 2, member 15p15.31
TBC1D30TBC1 domain family, member 3012q14.3
TBC1D5TBC1 domain family, member 53p24.3
TBC1D7TBC1 domain family, member 76p24
TBL1XTransducin-β-like 1, X-linkedXp22.31
TBL1XR1Transducin-β-like 1 receptor 13q26.32
TBR1T-box, brain, 12q24.2
TBX1T-box 122q11.21
TCF3Transcription factor 319p13.3
TCF4Transcription factor 418q21.2
TCF20Transcription factor 20 (AR1)22q13.2
TCF7L2Transcription factor 7-like 2 (t-cell specific, HMG-box)10q25.2
TDO2Tryptophan 2,3-dioxygenase4q32.1
TGM3Transglutaminase 320p13
THTyrosine hydroxylase11p15.5
THBS1Thrombospondin 115q14
THRAThyroid hormone receptor, α-117q21.1
TLK2Tousled-like kinase 217q23.2
TLX1T-cell leukemia homeobox 110q24.31
TM4SF20Transmembrane 4 L6 family, member 202q36.3
TMEM231Transmembrane protein 23116q23.1
TMLHEEpsilon-trimethyllysine hydroxylaseXq28
TNIP2TNFAIP3 interacting protein 24p16.3
TNRC6BTrinucleotide repeat containing 6B22q13.1
TOMM20MAS20P, S. cerevisiae, homolog of1q42.3
TOP1Topoisomerase, DNA, I20q12
TOP3BTopoisomerase, DNA, III, β22q11.22
TOPBP1Topoisomerase (DNA) II-binding protein 13q22.1
TOPORSTopoisomerase I-binding, arginine/serine-rich, E3 ubiquitin protein ligase9p21.1
TPH2Tryptophan hydroxylase 212q21.1
TPOThyroid peroxidase2p25.3
TRIM33Tripartite motif containing protein 331p13.2
TRIOTrio Rho guanine nucleotide exchange factor5p15.2
TRIP12Thyroid hormone receptor interactor 122q36.3
TRPC6Transient receptor potential cation channel, subfamily C, member 611q22.1
TRPM1Transient receptor potential cation channel, subfamily M, member 115q13.3
TSC1Tuberous sclerosis 19q34.1
TSC2Tuberous sclerosis 216p13.3
TSNTranslin2q14.3
TSPAN7Tetraspanin 7Xp11.4
TTI2TELO2-interacting protein 28p12
TTNTitin2q31.2
TUBA1ATubulin, α-1A12q13.12
TUBGCP5Tubulin-γ complex-associated protein 515q11.2
TYRTyrosinase 11q14.3
UBE1L2Ubiquitin-activating enzyme, E1-like 24q13.2
UBE2HUbiquitin-conjugating enzyme E2H 7q32.2
UBE3AUbiquitin protein ligase E3A15q11.2
UBE3BUbiquitin protein ligase E3B12q24.11
UBE3CUbiquitin protein ligase E3C7q36.3
UBL7Ubiquitin-like 715q24.1
UBR5Ubiquitin protein ligase E3 component N-recognin 58q22.3
UBR7Ubiquitin protein ligase E3 component N-recognin 7 14q32.12
UIMC1Ubiquitin interaction motif containing 15q35.2
UPB1Ureidopropionase, β 122q11.23
UPF2UPF2, yeast, homolog of 10p14
UPF3BUPF3, yeast, homolog of, BXq24
USP54Ubiquitin specific peptidase 5410q22.2
USP9YUbiquitin specific protease 9, Y-chromosomeYq11.21
VASH1Vasohibin 114q24.3
VCPValosin containing protein9p13.3
VIL1Villin 12q35
VIPVasoactive intestinal peptide (VIP)6q25.2
VPS13BVacuolar protein sorting 13, yeast, homolog of, B8q22.2
VPS4AVacuolar protein sorting 4 homolog A (S. cerevisiae)16q22.1
WACWW domain containing adaptor with coiled-coil10p12.1
WDFY3WD repeat and FYVE domain containing 34q21.23
WHSC1Wolf-Hirschhorn syndrome candidate 14p16.3
WNK3Protein kinase lysine deficient 3Xp11.22
WNT1Wingless-type MMTV integration site family, member 112q13.12
WNT2Wingless-type MMTV integration site family, member 27q31.2
WWC3WWC family member 3Xp22.32
XIRP1Cardiomyopathy-associated protein 13p22.2
XPCXeroderma pigmentosum complementation group C3p25.1
XPO1Exportin 12p15
XPO5Exportin 56p21.1
YEATS2YEATS domain containing 23q27.1
YTHDC2YTH domain containing 25q22.2
YWHAETyrosine 3-monooxygenase, tryptophan 5-monooxygenase activation protein, epsilon isoform17p13.3
ZBTB16Zinc finger- and BTB domain-containing protein 1611q23.1
ZBTB20Zinc finger- and BTB domain-containing protein 203q13.31
ZC3H12BZinc finger CCCH domain-containing protein 12BXq12
ZFPL1Zinc finger protein-like 111q13.1
ZMYND11Zinc finger, MYND-type containing 1110p15.3
ZNF18Zinc finger protein 1817p12
ZNF365Zinc finger protein 36510q21.2
ZNF385BZinc finger protein 385B2q31.3
ZNF407Zinc finger protein 40718q23
ZNF517Zinc finger protein 5178q24.3
ZNF8Zinc finger protein 819q13.43
ZNF713Zinc finger protein 7137p11.2
ZNF804AZinc finger protein 804A2q32.1
ZNF827Zinc finger protein 8274q31.22
ZSWIM5Zinc finger, SWIM-type containing 51p34.1

3. Experimental Section

We used computer-based internet websites and PubMed (https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/pubmed) to search key words for genetics and autism. This included the integrated catalogue of human genetic studies related to autism found at the Simons Foundation Autism Research Initiative (SFARI) website (https://gene.sfari.org), which currently lists 667 genes reported as of 25 February 2015. This public access initiative is an ongoing curated collection of clinically proven ASD genes supported by clinical and autism experts, medical geneticists and laboratory specialists in the study of autism. This site includes gene description and evidence of support for causation with cited literature reports. We examined peer-reviewed articles found in the medical literature following our search for genetic evidence (i.e., gene variants, mutations or disturbed gene function) and the involvement of genetics playing a role in autism. Sources included whole-genome sequencing of ASD families randomly selected with at least one unaffected sibling [40] or gene expression profiles in ASD [39] along with other informative websites (e.g., Online Mendelian Inheritance in Man, www.OMIM.org). We then compiled the list of genes from these major sources for a total of 792 genes, whereby at least one mechanism was involved for each gene that could lead to ASD, a heterogeneous condition involving many genes; as our report is focused on the compilation of ASD genes from peer-reviewed research articles and authoritative computer website genomic databases for autism and not necessarily related to causal relationships between the individual gene and ASD. Those genes recognized, to date, as playing a role in ASD susceptibility and causation generally appear to impact chromatin remodeling, metabolism, mRNA translation, cell adhesion and synaptic function [39].
SFARI is a publicly available manually curated web-based searchable site of human genes with links to ASD and includes genes in catalogue form based on five categories—genetic association, syndromic, rare single-gene variant and functional and multi-genetic copy number variation—supported by cited research publications for each. Additional literature sources in our study consisted of both primary research articles and reviews summarizing genetic evidence. Many of the listed genes were identified in multiple research studies and widely reported in literature reviews, data repositories and/or computer genomic-based websites for autism (e.g., SFARI). A large number of genes showed a varied relationship to autism and neurodevelopment, but the mass of the literature surveyed limits the reliability of our relative strength estimates for the ASD and gene associations. The gene would be included if cited and recognized in peer-reviewed publications (e.g., PubMed) with supportive genetic evidence (e.g., genetic linkage, GWAS, functional gene expression patterns, informative SNPs, CNVs or identified gene mutations). Other supporting genetic evidence can be found at Simons Foundation Autism Research Initiative (SFARI) at https://sfari.org/sfari-initiatives/simons-simplex-collection, the National Institutes of Health (NIH) at https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/gap, the Online Inheritance in Man (OMIM) at www.omim.org or Genecards at https://www.genecards.org.

4. Conclusions

Readily available tissue sources, such as peripheral blood, established lymphoblastoid cell lines and saliva, hold promise for more advances in ASD by enabling the identification of new genes and a better understanding of the causation and disease mechanisms to further stimulate research with the hope to discover new treatment modalities impacted by the recognition of known disease-causing or candidate genes for ASD. We illustrated the master list of clinically relevant and known ASD genes in our summary by plotting individual genes on high-resolution chromosome ideograms and generated a tabular form to increase the awareness required for genetic testing and counselling purposes for family members presenting for genetic services. Creating a master list of genes related to ASD is a complicated process; new genes are continually identified, but not all genes are equally important or certain to be causative. Additional research is needed to further investigate the causal relationships between the specific gene and ASD. The authors encourage the use of this collection of known and clinically relevant candidate genes for ASD in their evaluation of patients and families presenting for genetic testing options and for accurate genetic counselling.

Acknowledgments

We thank Carla Meister for expert preparation of the manuscript and Lorie Gavulic for excellent artistic design and preparation of chromosome ideograms. We acknowledge support from National Institute of Child Health and Human Development (NICHD) HD02528.

Author Contributions

Merlin G. Butler conceived of the study, reviewed data from ASD gene literature reports and wrote the manuscript; Syed K. Rafi obtained and reviewed articles pertaining to ASD genes and summarized the master gene list; and Ann M. Manzardo contributed to gene data review and interpretation, contributed to the content of the manuscript and reviewed the literature.

Conflicts of Interest

The authors declare no conflict of interest.

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