Table.
Genes with two or more de novo or rare inherited variants in probands with autism spectrum disorder and their associated gene ontology terms
| Gene name | Gene ontology terms | |
|---|---|---|
| ADNP56,58 | Activity-dependent neuroprotector homeobox |
Cellular nitrogen compound metabolic process, chromatin binding, DNA binding, ion binding, negative regulation of neuron apoptotic process,transcription, DNA-templated |
| ANK256,58 | Ankyrin 2, neuronal | ATPase binding, ion channel binding, potassium channel regulator activity, bridging, protein localisation to M-band, protein localisation to T-tubule, regulation of cardiac muscle cell membrane potential, response to methylmercury, SA node cell action potential, spectrin binding, structural constituent of cytoskeleton |
| ANKRD1158 | Ankyrin repeat domain 11 | Bone development, face morphogenesis, in utero embryonic development, multicellular organism growth, odontogenesisof dentin-containing tooth, protein binding |
| ARID1B56,58 | AT rich interactive domain IB (SWIl-like) |
Anatomical structure development, cellular nitrogen compound metabolic process, chromatin remodelling, chromatin-mediated maintenance of transcription, DNA binding, protein binding transcription factor activity, transcription coactivator activity |
| ASXL356 | Additional sex combs like transcriptional regulator 3 |
Cellular nitrogen compound metabolic process, DNA binding, ion binding, metal ion binding, regulation of transcription, DNA-templated |
| BCLllA56 | B-cellCLL/lymphoma 11A (zinc finger protein) |
DNA binding, ion binding, metal ion binding, negative regulation of dendrite development, negative regulation of protein homo-oligomerisation, nucleic acid binding transcription factor activity, protein heterodimerisation activity, protein sumoylation, RNA polymerase II core promoter proximal region sequence-specific DNA binding |
| CACNA2D356 | Calcium channel, voltage- dependent, alpha 2/delta subunit 3 |
Calcium ion transport, ion binding, metal ion binding, regulation of ion transmembrane transport, transmembrane transport, transport, voltage-gated calcium channel activity |
| CHD258 | Chromodomain helicase DNA binding protein 2 |
Anatomical structure development, ATP binding, ATP-dependent DNA helicase activity, ATPase activity, cellular nitrogen compound metabolic process, cellular response to DNA damage stimulus, chromatin modification, core promoter sequence-specific DNA binding, DNA binding, DNA duplex unwinding, DNA metabolic process, helicase activity |
| CHD856,58 | Chromodomain helicase DNA binding protein 8 |
Armadillo repeat domain binding, ATP-dependent chromatin remodelling, beta-catenin binding, canonical Wnt signalling pathway, DNA helicase activity, histone binding, in utero embryonic development, methylated histone binding, negative regulation of fibroblast apoptotic process, p53 binding, positive regulation of transcription from RNA polymerase II promoter |
| CUL356 | Cullin 3 | Cyclin binding, cyclin catabolic process, embryonic cleavage, enzyme binding, mitotic metaphase plate congression, negative regulation of Rho protein signal transduction, POZ domain binding, protein heterodimerisation activity, trophectodermal cellular morphogenesis, ubiquitin protein ligase binding, ubiquitin-protein transferase activity |
| DIP2A58 | DIP2 disco-interacting protein 2 homologue A (Drosophila) |
Catalytic activity, metabolic process, multicellular organismal development, negative regulation of gene expression, regulation of apoptotic process, transcription factor binding |
| DSCAM58 | Down syndrome cell adhesion molecule |
Anatomical structure development, cell adhesion, dendrite morphogenesis, dendrite self-avoidance, locomotory behaviour, negative regulation of cell adhesion, positive regulation of phosphorylation, post-embryonic retina morphogenesis in camera-type eye, protein binding |
| DYRK1A56,58 | Dual-specificity tyrosine- (Y)-phosphorylation regulated kinase 1A |
Circadian rhythm, cytoskeletal identical negative regulation of DNA damage response, signal transduction by p53 class mediator, non-membrane spanning protein tyrosine kinase activity, peptidyl-serine phosphorylation, peptidyl- threonine phosphorylation, peptidyl-tyrosine phosphorylation, positive regulation of protein deacetylation, protein autophosphorylation |
| FOXP158 | Forkhead box Pl | Cardiovascular system development, chromatin binding, in utero embryonic development, lung development, motor neuron axon guidance, negative regulation of transcription, DNA-templated, nucleic acid binding transcription factor activity, positive regulation of immunoglobulin production, positive regulation of mesenchymal cell proliferation |
| GIGYF158 | GRB10 interacting GYF protein 1 |
Insulin-like growth factor receptor signalling pathway, protein binding |
| GRIN2B56,58 | Glutamate receptor, ionotropic, N-methyl-D- aspartate 2B |
Calcium ion transport, cation channel activity, cation transmembrane transport, cell-cell signalling, detection of mechanical stimulus involved in sensory perception of pain, fear response, glutamate receptor signalling pathway, glycine binding, in utero embryonic development, ion binding, ionotropic glutamate receptor signalling pathway, neurological system process |
| KATNAL256,58 | Katanin p60 subunit A-like2 |
ATP binding, ATP catabolic process, ATPase activity, catabolic process, cellular nitrogen compound metabolic process, cytoskeletal DNA metabolic process, DNA recombination, DNA repair, four-way junction helicase activity, helicase activity, ion binding, microtubule binding, microtubule severing, microtubule-severing ATPase activity, response to stress |
| KDM5B58 | Lysine (K) -specific demethylase 5B |
Cellular nitrogen compound metabolic process, cellular protein modification process, DNA binding, histone demethylase activity (H3-K4 specific), histone H3-K4 demethylation, negative regulation of transcription, DNA-templated, nucleic acid binding transcription factor activity, oxidation-reduction process, oxidoreductase activity |
| KDM6B58 | Lysine (K) -specific demethylase 6B |
Beta-catenin binding, cardiac muscle cell differentiation, cell differentiation, cellular protein modification process, cellular response to hydrogen peroxide, dioxygenase activity, endothelial cell differentiation, histone demethylase activity (H3-K27 specific), histone demethylation, inflammatory response, ion binding, mesodermal cell differentiation, metal ion binding |
|
KMT2C (MLL3)56 |
Lysine (K) -specific methytransferase 2C |
Cellular nitrogen compound metabolic process, cellular protein modification process, DNA binding, histone methylation, histone methytransferase activity (H3-K4 specific), ion binding, methylation, methyltransferase activity, poly(A) RNA binding, RNA binding, signal transduction, transcription, DNA-templated, zinc ion binding |
| KMT2E58 | Lysine (K)-specific methyltransferase 2E |
Cell cycle arrest, cell differentiation, cellular nitrogen compound metabolic process, cellular protein modification process, cellular response to retinoic acid, DNA metabolic process, DNA methylation, enzyme binding, erythrocyte differentiation, histone H3-K4 methylation, histone methyltransferase activity (H3-K4 specific), immune system process, ion binding |
| MED13L58 | Mediator complex subunit 13-like |
Cellular nitrogen compound metabolic process, protein binding transcription factor activity, regulation of transcription from RNA polymerase II promoter, RNA polymerase II transcription cofactor activity, transcription from RNA polymerase II promoter |
| NCKAP158 | NCK-associated protein 1 | Anatomical structure development, apoptotic process, basal protein localisation, cell migration involved in gastrulation, embryonic body morphogenesis, embryonic foregut morphogenesis, endoderm development, enzyme binding, establishment or maintenance of actin cytoskeleton polarity, Fc-gamma receptor signalling pathway involved in phagocytosis, immune system process |
| PHF258 | PHD finger protein 2 | Calcium ion transport, ion binding, metal ion binding, regulation of ion transmembrane transport, transmembrane transport, transport, voltage-gated calcium channel activity |
| POGZ56,58 | Pogo transposable element with ZNF domain |
Cellular component assembly, chromosome organisation, DNA binding, ion binding, kinetochore assembly, metal ion binding, mitotic sister chromatid cohesion, nucleic acid binding, protein binding |
| RIMS158 | Regulating synaptic membrane exocytosis 1 |
Cell–cell signalling, cellular component assembly, enzyme binding, enzyme regulator activity, glutamate secretion, intracellular protein transport, ion binding, ion channel binding, membrane fusion, membrane organisation, metal ion binding, poly(A) RNA binding, positive regulation of gene expression, positive regulation of inhibitory postsynaptic membrane potential |
| SCN2A56,58 | Sodium channel, voltage gated, type II alpha subunit |
Intrinsic apoptotic signalling pathway in response to osmotic stress, ion transport, membrane depolarisation during action potential, nervous system development, neuron apoptotic process, sodium ion transmembrane transport, sodium ion transport, transmembrane transport, transmembrane transporter activity, transport, voltage-gated sodium channel activity |
| SUV420H156 | Suppressor of variegation 4–20 homologue 1 (Drosophila) |
Anatomical structure development, cellular nitrogen compound metabolic process, cellular protein modification process, histone methylation, histone methyltransferase activity (H4-K20 specific), methyltransferase activity, muscle organ development, regulation of transcription, DNA-templated |
| SYNGAP156 | Synaptic Ras GTPase activating protein 1 |
Dendrite development, enzyme regulator activity, GTPase activator activity, negative regulation of neuron apoptotic process, negative regulation of Ras protein signal transduction, pattern specification process, positive regulation of GTPase activity, Ras protein signal transduction, receptor clustering, regulation of synapse structure and activity, SH3 domain binding |
| TBR156,58 | T-box, brain, 1 | Axon guidance, cellular nitrogen compound metabolic process, commitment of neuronal cell to specific neuron type in forebrain, DNA binding, nucleic acid binding transcription factor activity, positive regulation of transcription from RNA polymerase II promoter, regulation of gene expression, RNA polymerase II core promoter sequence-specific DNA |
| TCF7L258 | Transcription factor 7-like 2 (T-cell specific, HMG- box) |
Armadillo repeat domain binding, beta-catenin binding, bone mineralisation, canonical Wnt signalling pathway, catenin import into nucleus, cell cycle arrest, cell proliferation, cellular nitrogen compound metabolic process, cellular response to starvation, chromatin binding, chromosome organisation, DNA binding, DNA metabolic process |
| TNRC6B58 | Trinucleotide repeat containing 6B |
Fc-epsilon receptor signalling pathway, gene expression, gene silencing by RNA, immune system process, innate immune response, neurotrophin TRK receptor signalling pathway, Notch signalling pathway, nucleotide binding, phosphatidylinositol-mediated signalling, poly(A) RNA binding, positive regulation of nuclear-transcribed mRNA catabolic process |
| WAC58 | WW domain containing adaptor with coiled-coil |
Cellular nitrogen compound metabolic process, cellular protein modification process, cellular response to DNA damage stimulus, chromatin binding, enzyme binding, G1 DNA damage checkpoint, histone H2B conserved C-terminal lysine ubiquitination, negative regulation of proteasomal ubiquitin-dependent protein catabolic process |
| WDFY358 | WD repeat and FYVE domain containing 3 |
1-phosphatidylinositol binding, aggrephagy, autophagy, beta-N-acetylglucosaminylglycopeptide beta-1,4- galactosyltransferase activity, catabolic process, ion binding, lipid binding, metal ion binding, response to stress |
The list of genes associated with autism spectrum disorder (ASD) was compiled from two original research papers that present a comprehensive statistical analysis of essentially all published ASD exomes sequenced to date,56,58 which also includes data from earlier work.57,59–61,63–65 The list includes genes that harbour two or more rare, de novo splice-site, nonsense, or frameshift variants in ASD probands or those with a false discovery rate of less than 0·05, calculated using the TADA method,56 which combines data on rare inherited or de novo damaging missense, splice-site, nonsense, or frameshift variants. Note that KDM5B has an equal count of de novo variants in unaffected siblings.58 The gene ontology (GO) terms for these genes—standardised descriptions of gene products that indicate associated biological processes, cellular components, and molecular functions—were obtained from Ensembl BioMart. The resulting list was shortened using REViGO to obtain a representative subset of GO terms using an algorithm that clusters by semantic similarities, avoiding redundancy. The highest-ranked biological processes and highest-ranked molecular function GO terms are listed for each gene.