MBD4

Chr 3ADAR

methyl-CpG binding domain 4, DNA glycosylase

Also known as: MED1, TPDS2, UVM1

NCBI Gene: 8930 ENSG00000129071 UniProt: O95243 OMIM: 603574

The protein encoded by this gene is a member of a family of nuclear proteins related by the presence of a methyl-CpG binding domain (MBD). These proteins are capable of binding specifically to methylated DNA, and some members can also repress transcription from methylated gene promoters. This protein contains an MBD domain at the N-terminus that functions both in binding to methylated DNA and in protein interactions and a C-terminal mismatch-specific glycosylase domain that is involved in DNA repair. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2013]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismAD/ARLOEUF 1.242 OMIM phenotypes

Clinical Summary— MBD4

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Gene-Disease Validity (ClinGen)

tumor predisposition syndrome 2 · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

140 unique Pathogenic / Likely Pathogenic· 761 VUS of 1348 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — MBD4

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.24LOEUF

pLI 0.000

Z-score 0.58

OE 0.88 (0.63–1.24)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.46Z-score

OE missense 0.92 (0.84–1.02)

270 obs / 292.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.88 (0.63–1.24)

0≤0.351.4

Missense OE?0.92 (0.84–1.02)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 23 / 26.2Missense obs/exp: 270 / 292.1Syn Z: -1.17

ClinVar Variant Classifications

1348 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic111

Likely Pathogenic29

VUS761

Likely Benign365

Benign15

Conflicting63

111

Pathogenic

Likely Pathogenic

761

VUS

365

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	109	0	2	0	111
Likely Pathogenic	28	1	0	0	29
VUS	14	690	45	12	761
Likely Benign	1	29	90	245	365
Benign	0	3	9	3	15
Conflicting	—				63
Total	152	723	146	260	1,344

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap MBD4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →