protein
Histone-lysine N-methyltransferase KMT5B
Gene
KMT5B
Organism
Homo sapiens(9606)
Length
885 aa
Mass
99,188 Da
KMT5B (histone-lysine N-methyltransferase KMT5B) is a histone methyltransferase that catalyzes methylation of lysine-20 on histone H4, converting H4K20me1 and H4K20me2 to H4K20me2 and H4K20me3 respectively (UniProt: Q4FZB7). This enzymatic activity regulates transcription, maintains genome integrity, and establishes constitutive heterochromatin, particularly in pericentric regions. The protein also facilitates DNA damage repair and participates in myogenesis through target gene regulation.
KMT5B functions broadly in chromatin remodeling and DNA repair pathways. It interacts with RB1 family proteins to target histone H3 and plays roles in non-homologous end-joining (NHEJ) DNA repair and potentially in class switch recombination. Mutations in KMT5B are associated with intellectual developmental disorder, autosomal dominant 51 (MRD51, MIM:617788), a condition characterized by significantly below-average general intellectual functioning and impaired adaptive behavior during development (UniProt: Q4FZB7).
KMT5B has been classified as a category 1 (high-confidence) autism spectrum disorder risk gene (SFARI Cat 1), indicating strong evidence for its involvement in autism etiology. This classification reflects the gene's critical role in neurodevelopmental processes and its connection to intellectual disability.
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 methyltransferase that specifically methylates monomethylated 'Lys-20' (H4K20me1) and dimethylated 'Lys-20' (H4K20me2) of histone H4 to produce respectively dimethylated 'Lys-20' (H4K20me2) and trimethylated 'Lys-20' (H4K20me3) and thus regulates transcription and maintenance of genome integrity (PubMed:24396869, PubMed:28114273). In vitro also methylates unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes (PubMed:24396869). H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression. Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions. KMT5B is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (By similarity). Plays a role in myogenesis by regulating the expression of target genes, such as EID3 (PubMed:23720823). Facilitates TP53BP1 foci formation upon DNA damage and proficient non-homologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (PubMed:28114273). May play a role in class switch reconbination by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity)
Disease associations
Intellectual developmental disorder, autosomal dominant 51MRD51
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
Sources
Last updated 5/6/2026, 5:25:32 AM