DMC1

Chr 22

DNA meiotic recombinase 1

Also known as: DMC1H, LIM15, dJ199H16.1

NCBI Gene: 11144ENSG00000100206UniProt: Q8IV36OMIM: 602721

The protein is a DNA recombinase essential for meiotic homologous recombination and repair of double-strand DNA breaks. Mutations cause autosomal recessive azoospermia and male infertility due to meiotic arrest during spermatogenesis. The gene shows very low constraint against loss-of-function variants, consistent with its specialized role in reproductive function rather than essential developmental processes.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.77
Clinical Summary— DMC1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 32 VUS of 69 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.77LOEUF
pLI 0.000
Z-score 2.41
OE 0.47 (0.29–0.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.27Z-score
OE missense 0.74 (0.65–0.85)
145 obs / 194.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.47 (0.29–0.77)
0≤0.351.4
Missense OE0.74 (0.65–0.85)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 11 / 23.6Missense obs/exp: 145 / 194.8Syn Z: -0.30
DN
0.74top 25%
GOF
0.4678th %ile
LOF
0.3163th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

69 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic6
VUS32
Likely Benign1
Benign1
Conflicting1
21
Pathogenic
6
Likely Pathogenic
32
VUS
1
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
19
0
21
Likely Pathogenic
0
3
3
0
6
VUS
0
30
2
0
32
Likely Benign
0
0
0
1
1
Benign
0
1
0
0
1
Conflicting
—1
Total03624162

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

View in ClinVar →

Protein Context — Lollipop Plot

DMC1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 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