Summary Statistics:
Gene Score:
Relevance to Autism
De novo missense variants in the SETD1A gene were identified in two ASD probands (Yuen et al., 2017), while a de novo likely gene-disruptive variant in this gene was observed in an ASD proband from the SPARK cohort (Feliciano et al., 2019). Kummeling et al., 2020 reported 15 individuals with de novo SETD1A variants presenting with a novel neurodevelopmental syndrome characterized by global developmental delay and/or intellectual disability, behavioral/psychiatric abnormalities, and craniofacial dysmorphisms; 3/14 individuals in this cohort presented with autistic behavior.
Molecular Function
The protein encoded by this gene is a component of a histone methyltransferase (HMT) complex that produces mono-, di-, and trimethylated histone H3 at Lys4. Trimethylation of histone H3 at lysine 4 (H3K4me3) is a chromatin modification known to generally mark the transcription start sites of active genes. The protein contains SET domains, a RNA recognition motif domain and is a member of the class V-like SAM-binding methyltransferase superfamily.
References
Primary
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder
ASD
Positive Association
Irritability
Support
Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses
ASD, DD, ID, epilepsy/seizures
Support
Genetic variants identification through whole-genome sequencing based on dried blood spots in 92 Chinese children with Autism.
ASD
Support
Genetic investigation of syndromic forms of obesity
DD, ID
Autistic features
Support
Genomic insights from a deeply phenotyped highly consanguineous neurodevelopmental disorders cohort
DD
Support
Deleterious coding variation associated with autism is shared across ancestries.
ASD
Support
Loss-of-function variants in the schizophrenia risk gene SETD1A alter neuronal network activity in human neurons through the cAMP/PKA pathway
Schizophrenia
Support
Next-generation phenotyping integrated in a national framework for patients with ultrarare disorders improves genetic diagnostics and yields new molecular findings
DD
ASD, epilepsy/seizures
Support
Whole-Exome Sequencing Identifies Novel Genetic Variants Associated with Unexplained Neurodevelopmental Disorders in Children
ASD
Support
Mutational Landscape of Autism Spectrum Disorder Brain Tissue
ASD
Support
The genetic landscape of autism spectrum disorder in the Middle Eastern population
ASD
Support
De Novo Variants Predominate in Autism Spectrum Disorder
ASD
ID
Support
Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes
ASD
Support
Case report: De novo variant of SETD1A causes infantile epileptic spasms syndrome
DD, epilepsy/seizures
Support
Mutations of schizophrenia risk gene SETD1A dysregulate synaptic function in human neurons
Schizophrenia
Support
DD, ID
Autistic features
Support
Exome Study of Single Nucleotide Variations in Patients with Syndromic and Non-Syndromic Autism Reveals Potential Candidate Genes for Diagnostics and Novel Single Nucleotide Variants
ASD
Support
Integrating de novo and inherited variants in 42
ASD
Recent Recommendation
Genomic landscape of rare variants in a Chinese autism cohort and discovery of novel risk genes.
ASD
Recent Recommendation
Rare coding variants in ten genes confer substantial risk for schizophrenia
Schizophrenia
Recent Recommendation
Characterization of SETD1A haploinsufficiency in humans and Drosophila defines a novel neurodevelopmental syndrome
DD, ID
GEN1176R001
missense_variant
c.2740C>T
p.Pro914Ser
De novo
Simplex
GEN1176R002
missense_variant
c.4246G>A
p.Glu1416Lys
De novo
Multiplex
GEN1176R003
frameshift_variant
c.1381dup
p.Arg461ProfsTer18
De novo
GEN1176R004
stop_gained
c.109C>T
p.Gln37Ter
De novo
GEN1176R005
frameshift_variant
c.1014dup
p.Ala339ArgfsTer23
De novo
GEN1176R006
frameshift_variant
c.1144_1147del
p.Tyr382HisfsTer114
De novo
GEN1176R007
stop_gained
c.1363G>T
p.Glu455Ter
De novo
GEN1176R008
stop_gained
c.1495C>T
p.Gln499Ter
De novo
GEN1176R009
frameshift_variant
c.1602_1603del
p.Gly535AlafsTer12
De novo
GEN1176R010
frameshift_variant
c.2289dup
p.Val764SerfsTer61
De novo
GEN1176R011
stop_gained
c.2725G>T
p.Glu909Ter
De novo
GEN1176R012
stop_gained
c.2968C>T
p.Arg990Ter
De novo
GEN1176R013
frameshift_variant
c.3937_3947del
p.Pro1313AlafsTer17
Unknown
Not maternal
GEN1176R014
frameshift_variant
c.3982_3983del
p.Phe1328GlnfsTer5
De novo
GEN1176R015
splice_site_variant
c.4409-2A>G
De novo
GEN1176R016
missense_variant
c.4495T>G
p.Tyr1499Asp
De novo
GEN1176R017
splice_site_variant
c.4582-2_4582del
De novo
GEN1176R018
splice_site_variant
c.4582-2_4582del
De novo
GEN1176R019
synonymous_variant
c.252C>T
p.Asp84=
Unknown
GEN1176R020
missense_variant
c.2761G>A
p.Asp921Asn
Familial
Paternal
Extended multiplex
GEN1176R021
missense_variant
c.821C>T
p.Thr274Met
De novo
GEN1176R022
missense_variant
c.3935C>T
p.Ala1312Val
De novo
GEN1176R023
missense_variant
c.2481G>C
p.Trp827Cys
De novo
GEN1176R024
missense_variant
c.2690G>A
p.Arg897Gln
De novo
GEN1176R025
missense_variant
c.2968C>G
p.Arg990Gly
De novo
GEN1176R026
missense_variant
c.3316A>T
p.Thr1106Ser
De novo
GEN1176R027
splice_site_variant
c.4582-2_4582-1del
De novo
GEN1176R028
synonymous_variant
c.3012G>A
p.Ser1004=
De novo
Simplex
GEN1176R029
stop_gained
c.7C>T
p.Gln3Ter
Unknown
Not paternal
GEN1176R030
frameshift_variant
c.3005_3006del
p.Glu1002GlyfsTer20
De novo
Simplex
GEN1176R031
intron_variant
c.870-10T>G
De novo
Unknown
GEN1176R032
missense_variant
c.4010A>C
p.Glu1337Ala
De novo
GEN1176R033
stop_gained
c.4618C>T
p.Gln1540Ter
De novo
GEN1176R034
missense_variant
c.4169G>A
p.Arg1390Gln
Unknown
GEN1176R035
missense_variant
c.2189A>G
p.Tyr730Cys
Unknown
Unknown
GEN1176R036
frameshift_variant
c.4879del
p.Val1627TrpfsTer41
De novo
GEN1176R037
synonymous_variant
c.663C>T
p.Ser221=
De novo
GEN1176R038
missense_variant
c.644_645delinsCC
p.Glu215Ala
De novo
Simplex
GEN1176R039
missense_variant
c.3362C>T
p.Pro1121Leu
Unknown
GEN1176R040
missense_variant
c.1688G>A
p.Arg563Gln
De novo
Simplex
GEN1176R041
missense_variant
c.3290C>T
p.Pro1097Leu
De novo
Unknown
GEN1176R042
missense_variant
c.3602G>A
p.Arg1201Gln
De novo
GEN1176R043
missense_variant
c.395G>A
p.Arg132His
De novo
Simplex
GEN1176R044
synonymous_variant
c.939C>T
p.His313=
De novo
Multiplex
GEN1176R045
missense_variant
c.1765G>A
p.Asp589Asn
De novo
Simplex
GEN1176R046
frameshift_variant
c.2114delinsGC
p.Gly708ArgfsTer117
De novo
Simplex
GEN1176R047
stop_gained
c.2422C>T
p.Arg808Ter
De novo
Unknown
GEN1176R048
stop_gained
c.2422C>T
p.Arg808Ter
De novo
Simplex
GEN1176R049
missense_variant
c.2461G>A
p.Gly821Arg
De novo
Simplex
GEN1176R050
frameshift_variant
c.2651_2653delinsT
p.Ala887ProfsTer21
De novo
Simplex
GEN1176R051
missense_variant
c.3454T>G
p.Ser1152Ala
De novo
Simplex
GEN1176R052
missense_variant
c.3470T>A
p.Leu1157His
De novo
Simplex
GEN1176R053
missense_variant
c.3863G>A
p.Arg1288His
De novo
Multiplex
GEN1176C001
intron_variant
rs2054213
c.247-778A>T
105,975 cases with self-reported irritability and 273,531 controls (all of European ancestry) from the UK Biobank
Discovery
16
Deletion-Duplication
151
No Interactions Available
