MBTD1

Chr 17

mbt domain containing 1

Also known as: SA49P01

NCBI Gene: 54799ENSG00000011258UniProt: Q05BQ5

The protein functions as a chromatin reader component of the NuA4 histone acetyltransferase complex, specifically binding methylated histone H4K20 to promote DNA double-strand break repair via homologous recombination. Loss-of-function mutations in MBTD1 are predicted to cause disease through haploinsufficiency, given the extremely high constraint against loss-of-function variants (pLI ~1.0, LOEUF 0.077). However, the specific clinical phenotype and inheritance pattern associated with MBTD1 mutations have not been established in the provided data.

Summary from RefSeq, UniProt, Mechanism
Research Assistant →
0
Active trials
5
Pubs (1 yr)
11
P/LP submissions
0%
P/LP missense
0.08
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— MBTD1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 69 VUS of 92 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.08LOEUF
pLI 1.000
Z-score 5.76
OE 0.00 (0.00–0.08)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.45Z-score
OE missense 0.46 (0.40–0.53)
150 obs / 324.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.08)
0≤0.351.4
Missense OE0.46 (0.40–0.53)
0≤0.61.4
Synonymous OE0.90
0≤1.21.6
LoF obs/exp: 0 / 38.6Missense obs/exp: 150 / 324.9Syn Z: 0.85
DN
0.2598th %ile
GOF
0.4085th %ile
LOF
0.81top 5%

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

LOFprediction above median · LOEUF 0.08

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

92 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS69
Likely Benign1
10
Pathogenic
1
Likely Pathogenic
69
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
1
0
1
VUS
0
69
0
0
69
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total07011081

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

View in ClinVar →

Protein Context — Lollipop Plot

MBTD1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients