protein
Lysine-specific demethylase 6A
Gene
KDM6A
Organism
Homo sapiens(9606)
Length
1401 aa
Mass
154,177 Da
KDM6A (lysine-specific demethylase 6A) is a histone demethylase that catalyzes removal of methyl groups from lysine-27 of histone H3, playing a central role in histone code regulation and chromatin organization (UniProt: O15550). This demethylation activity is coupled with histone H3 lysine-4 methylation and regulates recruitment of the PRC1 complex, thereby influencing gene expression and development. The protein also functions in demethylase-independent chromatin remodeling to regulate T-box family-dependent transcription.
KDM6A is involved in posterior development through regulation of HOX gene expression. Mutations in KDM6A cause Kabuki syndrome 2 (KABUK2), a congenital disorder characterized by intellectual disability, postnatal growth restriction, distinctive facial features including long palpebral fissures and eversion of the lower eyelids, cleft palate, skeletal abnormalities, and recurrent otitis media (UniProt: O15550).
KDM6A is classified as a syndromic autism-risk gene in the SFARI database (SFARI Cat S), indicating a curated association with autism spectrum disorder within a broader syndromic context rather than as a primary genetic risk factor for non-syndromic autism.
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 demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code (PubMed:17713478, PubMed:17761849, PubMed:17851529). Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-27' (PubMed:17713478, PubMed:17761849, PubMed:17851529). Plays a central role in regulation of posterior development, by regulating HOX gene expression (PubMed:17851529). Demethylation of 'Lys-27' of histone H3 is concomitant with methylation of 'Lys-4' of histone H3, and regulates the recruitment of the PRC1 complex and monoubiquitination of histone H2A (PubMed:17761849). Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression (By similarity)
Disease associations
Kabuki syndrome 2KABUK2
A congenital intellectual disability syndrome with 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.
Sources
Last updated 5/6/2026, 5:24:30 AM