Table 1.
Characteristics of risk genes implicated in both autism and cancer
| Gene name |
aliases | Human chrom location |
Protein function | Interacting proteins |
Autism related neurodevelopmental syndrome |
Cancer susceptibility or pathway |
Refs (PMID) |
|---|---|---|---|---|---|---|---|
| ADNP | Activity-dependent neuroprotector homeobox | 20q13.13 | Potential transcription factor. May mediate some of the neuroprotective peptide VIP-associated effects | SMARCA4, SMARCC2, ARID1A | Helsmoortel-van der Aa syndrome | p53, WNT | 25891009 |
| ANK2 | Ankyrin 2, Neuronal | 4q25 | Attaches integral membrane proteins to cytoskeletal elements and regulates cell motility, activation, proliferation, and contact | DMD, DCTN4, ACTF1 | Long (Electrocardiographic) QT Syndrome 4 | proteoglycans | 25863124 |
| ARID1B | AT Rich Interacting Domain 1B (SWI1-like), BRG1-Binding protein | 6q25.3 | Subunit of SWI/SNF chromatin remodelimg complex | ARID1A, SMARCA2, RELB, SMAD9, ASF1A | Coffin-Siris syndrome | ESR1, WNT; prostate cancer | 25891009 |
| ASH1L | Lysine N-Methyltransferase 2H | 1q22 | Histone methyltransferase specifically methylating Lys-36 of histone H3 (H3K36me) | SMAD7, HIST1H3A | Autism, susceptibility | Lysine degradation | 26402605 |
| ATRX | RAD54, Alpha Thalassemia/Mental Retardation Syndrome X-linked | Xq21.1 | SWI/SNF ATP-dependent DNA motor protein that acts in heterochromatin and telomere | CBX5, DAXX, HDAC1, SMC1A, SMC3 | Alpha-thalassemia/mental retardation syndrome | breast cancer, telomeres | 24779060 |
| CHD2 | Chromodomain Helicase DNA Binding Protein 2, ATP-dependent helicase | 15q26.1 | SWI/SNF ATP-dependent DNA motor protein that acts as a chromatin remodeling factor and transcriptional regulator, also DNA repair | SUMO1, PARK7 | Epileptic encephalopathy, childhood-onset | Chromatin regulation | 25891009 |
| CHD7 | Chromodomain Helicase DNA Binding Protein 7, ATP-dependent helicase | 8q12.2 | SWI/SNF ATP-dependent DNA motor protein that acts as a chromatin remodeling factor and transcriptional regulator | CHD8, PBRM1, SMARCC1, SMARCC2, SMARCE1 | CHARGE syndrome | WNT signalling, chromatin regulation | 24768552 |
| CHD8 | Chromodomain Helicase DNA Binding Protein 8, HELSNF1, AUTS18 | 14q11.2 | SWI/SNF ATP-dependent DNA motor protein that acts as a chromatin remodeling factor and transcriptional regulator | RBBP5, WDR5, CTNNB1, USF1, CTCF | Autism, susceptibility | WNT signalling, chromatin regulation | 25891009 |
| CUL3 | Cullin 3 | 2q36.2 | Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex | KLHL3, NEDD8, KEAP1, RBX1, CASP8 | Autism, susceptibility | WNT signalling, chromatin regulation | 25363768 |
| DNMT3A | DNA (5-cytosine)-methyltransferase 3A | 2p23.3 | Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development | DNMT3L, DNMT3B, UHRF1 | Autism, susceptibility | Chromatin regulation | 26402605 |
| DYRK1A | Dual-specificity tyrosine phosphorylation-regulated kinase 1A | 21q22.13 | serine/threonine kinase implicated in cell survival, proliferation and differentiation | HIPK2, SFN, YWHAB, YWHAE, DCAF | Down syndrome, mental retardation, autosomal dominant 7 | NOTCH signalling, translation regulation | 17583556 |
| EHMT1 | Euchromatic Histone-Lysine N-Methyltransferase, KMT1D, CLP | 9q34.3 | Histone methyltransferase of H3K9me and H3K9me2 in euchromatin | MDM2, p53, SUV39H1, HIST1H3A, CTBP1, SUV39H1 | Kleefstra syndrome | cellular senescence, NOTCH, lysine degradation | 24779060 |
| ERBB2IP | ERBB2 Interacting protein | 5q12.3 | Acts as an adapter for the receptor ERBB2, inhibits NOD2-dependent NF-kappa-B signaling and proinflammatory cytokine secretion | ERBB2, SMAD2, SMAD3, NRG2, PKP4 | Autism, susceptibility | TGFb signalling, cervical and colon cancer | 26402605 |
| ERCC6 | Cockayne’s Syndrome B | 10q11.23 | SWI/SNF ATP-dependent DNA motor protein that acts in transcription-coupled DNA repair | Cockayne’s Syndrome-A/ERCC8 TFIIH, SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, MYBBP1A, DDX21, KIAA1530/UVSSA. | High confidence ASD candidate gene | transcription-coupled DNA repair | 24768552 |
| FOXP1 | Forkhead box P1 | 3p13 | Forkhead box transcription factor and putative tumor suppressor | CTBP1, FOXP2, FOXP4, MYC, NCOR2 | Autism, susceptibility | WNT, Notch signaling | 25363768 |
| HERC2 | HECT And RLD Domain Containing E3 Ubiquitin Protein Ligase 2 | 15q13 | E3 ubiquitin-protein ligase that regulates repair proteins on damaged chromosomes, regulates replication fork progression | UBE3A, SUMO1, RNF8, BRCA1 | Mental retardation, autosomal recessive 38 (MRT38) | Class I MHC Ag presentation and processing | 24779060 |
| HRAS | Harvey Rat Sarcoma Viral Oncogene Homolog, p21RAS | 11p15.5 | RAS oncogene family members that bind GTP and GDP, with intrinsic GTPase activity | RAF1, SOS1, RIN1, ABL2, CAV1 | Costello syndrome | oncogene, MAPK pathway | 24768552 |
| INTS6 | Integrator complex subunit 6, DICE1 | 13q14.3 | Component of the Integrator complex, involved in the small nuclear RNAs transcription and processing, tumor supressor | UPF1, UPF2, INTS1, INTS3, INTS8 | Autism, susceptibility | lung cancer | 26402605 |
| KDM5B | Lysine (K)-Specific Demethylase 5B, JARID1B | 1q32.1 | Histone demethylase that demethylates K4 of histone H3 | ARID1B, RB1, HDAC1, PAX9 | Autism, susceptibility | Retinoblastoma, chromatin regulation | 25363768 |
| KDM6B | Lysine (K)-Specific Demethylase 6B, JMJD3 | 17p13.1 | Histone demethylase that specifically demethylates K27 of histone H3 | ESR1, CSNK2B, HIST1H3D | Autism, susceptibility | Chromatin regulation | 25363768 |
| KMT2C | Lysine (K)-Specific Methyltransferase 2C, MLL3 | Histone methyltransferase that methylates K4 of histone H3 | NCOA6, ASCL2, ASH2L, AK1, TSC22D1 | Autism, susceptibility | Lysine degradation | 26402605 | |
| KMT2D | MLL2 | 12q13.12 | Histone methylatransferase of K4me | ESR1, PAXIPI, RBBP5, SMAD1, SMAD9 | Kabuki syndrome | Lysine degradation | 25891009 |
| MECP2 | Methyl CpG binding protein 2, AUTSX3 | Xq28 | chromosomal protein and transcriptional regulator that binds to methylated DNA | SIN3A, SMARCA2, ATRX | Rett syndrome | Chromatin regulation | 24779060 |
| MET | AUTS9, HGFR, c-Met | 7q31 | Receptor tyrosine kinase that transduces signals from ECM by binding HGF, activates RAS-ERK, AKT, or PLC pathways | HGF, CBL, GRB2, UBC, PTPN1 | Autism, association | Hereditary papillary renal carcinoma (RCCP), glioma, | 19548256 |
| MIB1 | Mindbomb E3 Ubiquitin Protein Ligase 1 | 18q11.2 | E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins | NOTCH1, UBC, UBE2N, DAPK1 | Autism, susceptibility | Notch signaling | 26402605 |
| NF1 | Neurofibromin 1, NFNS | 17q11.2 | Negative regulator of RAS signal pathway | GADD45A, SMARCC1, SMARCD1, GTF2A1 | Neurofibromatosis, type 1 | Leukemia, juvenile myelomonocytic (JMML), Ras, MAPK pathways | 24768552 |
| NIPBL | Nipped-B Homolog (Drosophila), CDLS1 | 5p13.2 | cohesion protein that facilitates enhancer-promoter interactions in Drosophila | SMC3, HDAC1, HDAC2, ATAD5 | Cornelia de Lange syndrome 1 | colorectal and gastric cancer | 24768552 |
| PAX5 | Paired Box 5, ALL3, BSAP | 9p13.2 | Paired box transcription factor involved in B cell development, neural development, spermatogenesis; recurrent translocations in lymphoma | EP300, CEBBP, ETS1, TBP, EBF1 | Autism, susceptibility | Leukemia, acute lymphoblastic, susceptibility (ALL3), WNT pathway | 25418537 |
| PHF2 | PHD Finger Protein 2 | 9q22.31 | Lysine histone demethylase that is recruited to trimethylated Lys-4 of histone H3 (H3K4me3) at rDNA promoters and promotes expression of rDNA | TP53, RBBP7, SUZ12, EZH2 | Autism, susceptibility | Chromatin regulation | 26402605 |
| PTEN | MMAC1 | 10q23.3 | tumor suppressor, dual-specificity protein phosphatase | NEDD4, AKT1, PTK2, UBC, SLC9A3R1 | Macrocephaly/autism syndrome | Cowden syndrome, glioblastoma, mTOR pathway, recombinational DNA repair | 24768552 |
| PTK7 | Protein Tyrosine Kinase 7 (Inactive) | Inactive tyrosine kinase involved incononical and non-cononical Wnt signaling pathways, function in cell adhesion, cell migration, cell polarity, proliferation, actin cytoskeleton reorganization and apoptosis | DVL1, DVL2, DVL3, CTNNB1, WNT9B | Autism, susceptibility | WNT and AKT signaling | 26402605 | |
| SMC1A | Structural Maintenance Of Chromosomes 1A | Xp11.22 | chromosome cohesion during cell cycle and DNA repair | SMC3, RAD21, STAG2, SMC2, SSU72 | Cornelia de Lange syndrome 2 | genome maintenance, colorectal cancer | 24768552 |
| SMC2 | Structural Maintenance Of Chromosomes 2 | 9q31.1 | critical for mitotic chromosome condensation and for DNA repair | SMC1A, SMC4, NCAPH, NCAPH2, NCAPD2 | High confidence ASD candidate gene | Genome maintenance | 24768552 |
| SUV420H1 | Lysine N-Methyltransferase 5B, KMT5B | 11q13.2 | Histone methyltransferase that specifically trimethylates K20 of histone H4 | TP53BP1, NCOA2, YWHAQ | Autism, susceptibility | Lysine degradation | 26402605 |
| TBL1XR1 | Transducin (Beta)-Like 1 X-linked Receptor 1, TBLR1, IRA1 | 3q26.32 | F-box-like protein recruits ubiquitin/19S proteosome complex to nuclear hormone receptors, degradation of N-Cor for transcriptional activation | TBL1X, HDAC3, NCOR1, THRB, CACNA1C, CACNA1E | Autism, susceptibility | NOTCH1, PPARalpha metabolism | 26069883 |
| TCF7L2 | T-Cell-Specific Transcription Factor 4 | 10q25.2 | High mobility group (HMG) box-containing transcription factor that plays a key role in the Wnt signaling pathway | TCF7, CTNNB1, RUVBL2 | Autism, susceptibility | WNT signalling | 25363768 |
| TNRC6B | Trinucleotide Repeat Containing 6B | 22q13.1 | Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs) | TP53, AGO1, CDK4, EIF2C1 | Autism, susceptibility | PI-3K | 25363768 |
| TRIO | Trio Rho Guanine Nucleotide Exchange Factor | 5p15.2 | Promotes the exchange of GDP by GTP, coordinates cell-matrix and cytoskeletal rearrangements necessary for cell migration and cell growth | RAC1, RAC3, HCRTR2, DISC1, CDC5L | Autism, susceptibility | NOTCH, Rho GTPase | 26402605 |
| TRIP12 | Thyroid hormone receptor interating protein, E3 Ubiquitin-Protein Ligase For Arf | 2q36.3 | E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation pathway, suppresses spreading of Ub-chromatin at damaged chromosomes | MYC, TRADD, SMARCC1, CDKN2A, SMARCE1, THRB, PSMC5, TMEFF2 | Autism, susceptibility | Class I MHC Ag presentation and processing | 25418537 |
| TSC1 | Tuberous Sclerosis 1, LAM | 9q34.13 | Negative regulation of mTORC1 signalling | TSC2, MAPK1, RHEB, AKT1, IKBKB | Tuberous sclerosis | MTOR, AKT pathway | 24768552 |
| TSC2 | Tuberous Sclerosis 2, TSC4, LAM | 16p13.3 | Negative regulation of mTORC1 signalling | TSC1, RHEB, YWHAZ, YWAB | Tuberous sclerosis | MTOR, AKT pathway | 24768552 |
| UBE3A | E6AP Ubiquitin-Protein Ligase, ANCR | 15q11.2 | E3 ubiquitin-protein ligase, cofactor for nuclear hormone receptors, maternal mutations cause Angelman syndrome, imprinted in brain, in cervical cancer degrades p53 in presence of E6 | RAD23A, HERC2, RING1B, ESR1, RARA | Angelman syndrome (del), Dup15q syndrome (dup) | Class I MHC Ag presentation and processing, PEDF, estrogen | 24779060 |
| WAC | WW Domain Containing Adaptor With Coiled-Coil | 10p12.1 | Acts as a linker between gene transcription and histone H2B monoubiquitination at K120 | UBC, UBQLN4, POL2R2A | Autism, susceptibility | chromatin regulation | 26402605 |
*
Genes summarized in Table 1 were identified as autism risk genes from publications in the cited references identified by PIMD numbers in the far right column. Information describing each gene was assembled from sources compiled within GeneCards and OMIM databases.