protein
Lysine-specific demethylase 6B
Gene
KDM6B
Organism
Homo sapiens(9606)
Length
1643 aa
Mass
176,632 Da
KDM6B (lysine-specific demethylase 6B) is a histone demethylase that catalyzes removal of methyl groups from lysine 27 of histone H3, a modification central to epigenetic gene regulation (UniProt: O15054). The enzyme plays key roles in posterior development through HOX gene expression regulation and participates in inflammatory responses during macrophage differentiation. It also functions in chromatin remodeling independent of its demethylase activity, linking T-box transcription factors to the SWI/SNF complex.
KDM6B is widely expressed and involved in multiple developmental and immune processes. Pathogenic variants in KDM6B cause Stolerman neurodevelopmental syndrome (NEDSST), an autosomal dominant disorder characterized by global developmental delay, intellectual disability, language impairment, and distinctive facial features including a prominent nasal bridge. Additional clinical features may include musculoskeletal abnormalities and autism spectrum disorder in some patients.
KDM6B is classified as a Category 1 (high confidence) SFARI gene with syndromic autism association (SFARI Cat 1). This designation reflects strong genetic evidence linking KDM6B mutations to neurodevelopmental pathology, including autism as a feature of NEDSST in affected individuals.
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
Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code (PubMed:17713478, PubMed:17825402, PubMed:17851529, PubMed:18003914). Demethylates trimethylated and dimethylated H3 'Lys-27' (PubMed:17713478, PubMed:17825402, PubMed:17851529, PubMed:18003914). Plays a central role in regulation of posterior development, by regulating HOX gene expression (PubMed:17851529). Involved in inflammatory response by participating in macrophage differentiation in case of inflammation by regulating gene expression and macrophage differentiation (PubMed:17825402). Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression by acting as a link between T-box factors and the SMARCA4-containing SWI/SNF remodeling complex (By similarity)
Disease associations
Stolerman neurodevelopmental syndromeNEDSST
An autosomal dominant disorder characterized by global developmental delay, variable intellectual disability, poor language acquisition, and dysmorphic facial features including a prominent nasal bridge and coarse features. Some patients manifest autism spectrum disorder. Musculoskeletal features may be present and include widened and thickened hands and fingers, joint hypermobility, clinodactyly of the fifth fingers, and toe syndactyly.
Sources
Last updated 5/6/2026, 5:25:33 AM