protein
Histone-lysine N-methyltransferase SETD5
Gene
SETD5
Organism
Homo sapiens(9606)
Length
1442 aa
Mass
157,515 Da
SETD5 is a histone-lysine N-methyltransferase that functions as a chromatin regulator essential for brain development (UniProt: Q9C0A6). The protein regulates neural stem cell proliferation and synaptic transmission by controlling RNA elongation rate, primarily through mediating trimethylation of histone H3 at lysine 36 (H3K36me3). It also exhibits in vitro monomethylation activity at H3K9me1, though the functional relevance of its methyltransferase activity remains subject to discussion.
SETD5 mutations are associated with intellectual developmental disorder, autosomal dominant 23 (MRD23), characterized by moderate to severe intellectual disability with variable craniofacial features including brachycephaly, depressed nasal bridge, and micrognathia (UniProt: Q9C0A6). Affected individuals frequently exhibit behavioral problems including obsessive-compulsive disorder and hand flapping with ritualized behaviors.
SETD5 is classified as SFARI Category 1 with syndromic features (SFARI Cat 1), indicating strong evidence for autism association. Autism is documented as a prominent behavioral feature in patients with MRD23 caused by SETD5 mutations, establishing direct relevance to autism spectrum disorder in the context of intellectual disability and developmental disorders.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
High confidence — strong genetic evidence from multiple studies
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Chromatin regulator required for brain development: acts as a regulator of RNA elongation rate, thereby regulating neural stem cell (NSC) proliferation and synaptic transmission. May act by mediating trimethylation of 'Lys-36' of histone H3 (H3K36me3), which is essential to allow on-time RNA elongation dynamics. Also monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro. The relevance of histone methyltransferase activity is however subject to discussion
Disease associations
Intellectual developmental disorder, autosomal dominant 23MRD23
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD23 patients manifest moderate to severe intellectual disability with additional variable features of brachycephaly, a low hairline, depressed nasal bridge, prominent high nasal root, tubular nose, upslanting palpebral fissures, long and smooth philtrum, micrognathia, thin upper lip, and crowded teeth. Behavioral problems, including obsessive-compulsive disorder, hand flapping with ritualized behavior, and autism, are prominent features.
Sources
Last updated 5/6/2026, 5:25:18 AM