protein
Methyl-CpG-binding domain protein 5
Gene
MBD5
Organism
Homo sapiens(9606)
Length
1494 aa
Mass
159,895 Da
MBD5 (methyl-CpG-binding domain protein 5) is a non-catalytic component of the polycomb repressive deubiquitinase (PR-DUB) complex that mediates deubiquitination of histone H2A at lysine 120 (UniProt: Q9P267). The protein stabilizes PR-DUB components and stimulates their ubiquitinase activity, functioning as an epigenetic regulator that associates with chromatin regions enriched in specific histone marks including H3K4me1, H3K4me3, and H3K27Ac.
The PR-DUB complex, through MBD5, regulates genes involved in cell growth, development, cell communication, signaling, and cell proliferation. MBD5-containing complexes associate with distinct chromatin regions that may differ functionally from MBD6-containing complexes. The protein is associated with intellectual developmental disorder, autosomal dominant 1 (MRD1), characterized by significantly below average general intellectual functioning and impairments in adaptive behavior during development (UniProt: Q9P267).
MBD5 is classified as SFARI Category 1 with a syndromic autism association (SFARI Cat 1), indicating high confidence evidence for involvement in autism spectrum disorder, particularly in syndromic presentations.
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
Non-catalytic component of the polycomb repressive deubiquitinase (PR-DUB) complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-120' (H2AK119ub1) (PubMed:24634419). Important for stability of PR-DUB components and stimulating its ubiquitinase activity (PubMed:36180891). As part of the PR-DUB complex, associates with chromatin enriched in histone marks H3K4me1, H3K4me3, and H3K27Ac, but not in H3K27me3 (PubMed:36180891). The PR-DUB complex is an epigenetic regulator of gene expression, including genes involved in cell growth and survivability (PubMed:36180891). MBD5 and MBD6 containing complexes associate with distinct chromatin regions enriched in genes involved in different pathways (PubMed:36180891). Heterochromatin recruitment is not mediated by DNA methylation (PubMed:20700456). The PR-DUB complex is an epigenetic regulator of gene expression, including genes involved in development, cell communication, signaling, cell proliferation and cell viability (PubMed:36180891)
Disease associations
Intellectual developmental disorder, autosomal dominant 1MRD1
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, 5:25:30 AM