MBD2

Chr 18

methyl-CpG binding domain protein 2

Also known as: DMTase, NY-CO-41

MBD2 encodes a methyl-CpG-binding domain protein that binds to methylated DNA and functions as a transcriptional repressor by recruiting histone deacetylases and chromatin remodeling complexes. The gene has a LOEUF score of 0.522, indicating moderate constraint against loss-of-function variants, but no well-established Mendelian disorders have been definitively linked to MBD2 mutations in current clinical practice. MBD2 is part of the methyl-CpG-binding protein family that regulates gene expression through DNA methylation-dependent mechanisms.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
38
Pubs (1 yr)
54
P/LP submissions
0%
P/LP missense
0.52
LOEUF
LOF
Mechanism· predicted
Clinical SummaryMBD2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
52 unique Pathogenic / Likely Pathogenic· 51 VUS of 119 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.350
Z-score 2.99
OE 0.23 (0.110.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.11Z-score
OE missense 0.53 (0.440.64)
85 obs / 160.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.23 (0.110.52)
00.351.4
Missense OE0.53 (0.440.64)
00.61.4
Synonymous OE0.82
01.21.6
LoF obs/exp: 4 / 17.5Missense obs/exp: 85 / 160.2Syn Z: 1.06
DN
0.4388th %ile
GOF
0.3292th %ile
LOF
0.73top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

119 submitted variants in ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic2
VUS51
Benign1
50
Pathogenic
2
Likely Pathogenic
51
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
50
0
50
Likely Pathogenic
0
0
2
0
2
VUS
0
48
3
0
51
Likely Benign
0
0
0
0
0
Benign
0
0
0
1
1
Total048551104

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MBD2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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