MBD5

Chr 2

methyl-CpG binding domain protein 5

Also known as: C2DELq23.1, DEL2Q23.1, MRD1

NCBI Gene: 55777 ENSG00000204406 UniProt: Q9P267

The protein binds specifically to methylated DNA and interacts with the polycomb repressive complex PR-DUB to regulate histone deubiquitination. Haploinsufficiency causes autosomal dominant intellectual developmental disorder characterized by microcephaly, intellectual disabilities, severe speech impairment, and seizures. The pathogenic mechanism involves loss of function mutations leading to reduced gene expression.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the methyl-CpG-binding domain (MBD) family. The MBD consists of about 70 residues and is the minimal region required for a methyl-CpG-binding protein binding specifically to methylated DNA. In addition to the MBD domain, this protein contains a PWWP domain (Pro-Trp-Trp-Pro motif), which consists of 100-150 amino acids and is found in numerous proteins that are involved in cell division, growth and differentiation. Mutations in this gene cause an autosomal dominant type of cognitive disability. The encoded protein interacts with the polycomb repressive complex PR-DUB which catalyzes the deubiquitination of a lysine residue of histone 2A. Haploinsufficiency of this gene is associated with a syndrome involving microcephaly, intellectual disabilities, severe speech impairment, and seizures. Alternatively spliced transcript variants have been found, but their full-length nature is not determined. [provided by RefSeq, Jul 2017]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, autosomal dominant 1

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.14

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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