protein
Histone-lysine N-methyltransferase 2D
aka Lysine N-methyltransferase 2D
Gene
KMT2D
Organism
Homo sapiens(9606)
Length
5537 aa
Mass
593,389 Da
KMT2D (Histone-lysine N-methyltransferase 2D) is a chromatin-modifying enzyme that catalyzes methylation of histone H3 at lysine 4 (H3K4), predominantly generating H3K4me1 marks at active chromatin regions involved in transcription and DNA repair (UniProt: O14686). The protein also functions as a coactivator for estrogen receptor signaling through recruitment by ESR1.
KMT2D is part of the chromatin remodeling machinery and is expressed across tissues where transcriptional regulation is required. Biallelic and heterozygous mutations in KMT2D cause distinct disease phenotypes: autosomal dominant Kabuki syndrome 1 (KABUK1), characterized by intellectual disability, distinctive facial features, postnatal growth abnormalities, skeletal changes, and recurrent infections; and branchial arch abnormalities syndrome (BCAHH), characterized by choanal atresia, athelia, hearing loss, and thyroid dysfunction with potential developmental delay.
KMT2D is classified as a syndromic autism-associated gene in the SFARI database (SFARI Cat S), indicating evidence for involvement in autism within the context of broader genetic syndromes such as Kabuki syndrome, where developmental and intellectual features overlap with autism spectrum phenotypes.
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 catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17500065, PubMed:25561738). Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription (PubMed:16603732)
Disease associations
Kabuki syndrome 1KABUK1
An autosomal dominant, congenital syndrome characterized by intellectual disability and additional features, including postnatal dwarfism, a peculiar facies characterized by long palpebral fissures with eversion of the lateral third of the lower eyelids, a broad and depressed nasal tip, large prominent earlobes, a cleft or high-arched palate, scoliosis, short fifth finger, persistence of fingerpads, radiographic abnormalities of the vertebrae, hands, and hip joints, and recurrent otitis media in infancy.
Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndromeBCAHH
An autosomal dominant disorder characterized by choanal atresia, athelia or hypoplastic nipples, branchial sinus abnormalities, neck pits, lacrimal duct anomalies, hearing loss, external ear malformations, delayed or absent pubertal development, and thyroid abnormalities. Additional features may include developmental delay, growth failure and short stature.
Sources
Last updated 5/6/2026, 5:24:31 AM