MBD5
Chr 2ADmethyl-CpG binding domain protein 5
Also known as: C2DELq23.1, DEL2Q23.1, MRD1
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.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 11 | 0 | 6 | 0 | 17 |
Likely Pathogenic | 5 | 1 | 8 | 0 | 14 |
VUS | 1 | 324 | 12 | 3 | 340 |
Likely Benign | 0 | 7 | 22 | 76 | 105 |
Benign | 0 | 0 | 1 | 0 | 1 |
Conflicting | — | 7 | |||
| Total | 17 | 332 | 49 | 79 | 484 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MBD5 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
RECRUITINGRare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
RECRUITINGExternal Resources
Links to major genomics databases and tools