protein
Histone-lysine N-methyltransferase, H3 lysine-36 specific
Gene
NSD1
Organism
Homo sapiens(9606)
Length
2696 aa
Mass
296,652 Da
NSD1 encodes a histone-lysine N-methyltransferase that specifically dimethylates lysine 36 of histone H3 (H3K36me2) (UniProt: Q96L73). This epigenetic modifier functions as a transcriptional intermediary factor capable of both positive and negative effects on gene expression depending on cellular context.
NSD1 is associated with two major genetic overgrowth syndromes. Mutations cause Sotos syndrome (OMIM 117550), an autosomal dominant condition featuring pre- and postnatal overgrowth, developmental delay, intellectual disability, advanced bone age, and distinctive craniofacial features including macrocephaly with frontal bossing and sparse frontoparietal hair (UniProt: Q96L73). NSD1 alterations are also implicated in Beckwith-Wiedemann syndrome (OMIM 130650), characterized by abdominal wall defects, macroglossia, overgrowth, and tumor predisposition.
NSD1 carries SFARI classification of category S (syndromic) (SFARI Cat S), indicating a curated association with autism in the context of Sotos syndrome and related overgrowth disorders. The histone-modifying function and developmental phenotypes suggest plausible mechanisms linking NSD1 dysfunction to neurodevelopmental features in syndromic presentations.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
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
Histone methyltransferase that dimethylates Lys-36 of histone H3 (H3K36me2). Transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context
Disease associations
Sotos syndromeSOTOS
An autosomal dominant, childhood overgrowth syndrome characterized by pre- and postnatal overgrowth, developmental delay, intellectual disability, advanced bone age, and abnormal craniofacial morphology including macrodolichocephaly with frontal bossing, frontoparietal sparseness of hair, apparent hypertelorism, downslanting palpebral fissures, and facial flushing. Common oral findings include: premature eruption of teeth; high, arched palate; pointed chin and, more rarely, prognathism.
Beckwith-Wiedemann syndromeBWS
A disorder characterized by anterior abdominal wall defects including exomphalos (omphalocele), pre- and postnatal overgrowth, and macroglossia. Additional less frequent complications include specific developmental defects and a predisposition to embryonal tumors.
Sources
Last updated 5/6/2026, 5:24:36 AM