Human Gene Module / Chromosome 16 / SETD1A

SETD1ASET domain containing 1A, histone lysine methyltransferase

Score
3S
Suggestive Evidence, Syndromic Criteria 3.1, Syndromic
Autism Reports / Total Reports
2 / 3
Rare Variants / Common Variants
17 / 0
Aliases
SETD1A, EPEDD,  KMT2F,  Set1,  Set1A
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Syndromic
Chromosome Band
16p11.2
Associated Disorders
-
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.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBase
Reports related to SETD1A (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
2 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
3 Recent Recommendation Characterization of SETD1A haploinsufficiency in humans and Drosophila defines a novel neurodevelopmental syndrome Kummeling J et al. (2020) No -
Rare Variants   (17)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.109C>T p.Gln37Ter stop_gained De novo NA - 32346159 Kummeling J et al. (2020)
c.4409-2A>G - splice_site_variant De novo NA - 32346159 Kummeling J et al. (2020)
c.1363G>T p.Glu455Ter stop_gained De novo NA - 32346159 Kummeling J et al. (2020)
c.1495C>T p.Gln499Ter stop_gained De novo NA - 32346159 Kummeling J et al. (2020)
c.2725G>T p.Glu909Ter stop_gained De novo NA - 32346159 Kummeling J et al. (2020)
c.2968C>T p.Arg990Ter stop_gained De novo NA - 32346159 Kummeling J et al. (2020)
c.4582-2_4582del - splice_site_variant De novo NA - 32346159 Kummeling J et al. (2020)
c.4495T>G p.Tyr1499Asp missense_variant De novo NA - 32346159 Kummeling J et al. (2020)
c.2740C>T p.Pro914Ser missense_variant De novo NA Simplex 28263302 C Yuen RK et al. (2017)
c.4246G>A p.Glu1416Lys missense_variant De novo NA Multiplex 28263302 C Yuen RK et al. (2017)
c.1381dup p.Arg461ProfsTer18 frameshift_variant De novo NA - 31452935 Feliciano P et al. (2019)
c.1014dup p.Ala339ArgfsTer23 frameshift_variant De novo NA - 32346159 Kummeling J et al. (2020)
c.2289dup p.Val764SerfsTer61 frameshift_variant De novo NA - 32346159 Kummeling J et al. (2020)
c.1602_1603del p.Gly535AlafsTer12 frameshift_variant De novo NA - 32346159 Kummeling J et al. (2020)
c.3982_3983del p.Phe1328GlnfsTer5 frameshift_variant De novo NA - 32346159 Kummeling J et al. (2020)
c.1144_1147del p.Tyr382HisfsTer114 frameshift_variant De novo NA - 32346159 Kummeling J et al. (2020)
c.3937_3947del p.Pro1313AlafsTer17 frameshift_variant Unknown Not maternal - 32346159 Kummeling J et al. (2020)
Common Variants  

No common variants reported.

CNVs associated with SETD1A(1 CNVs)
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16p11.2 120 Deletion-Duplication 184  /  1584
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