DMC1

Chr 22

DNA meiotic recombinase 1

Also known as: DMC1H, LIM15, dJ199H16.1

NCBI Gene: 11144ENSG00000100206UniProt: Q8IV36

This gene encodes a member of the superfamily of recombinases (also called DNA strand-exchange proteins). Recombinases are important for repairing double-strand DNA breaks during mitosis and meiosis. This protein, which is evolutionarily conserved, is reported to be essential for meiotic homologous recombination and may thus play an important role in generating diversity of genetic information. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

Primary Disease Associations & Inheritance

UniProtDevelopmental and epileptic encephalopathy 105 with hypopituitarism
69
ClinVar variants
27
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DMC1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 32 VUS of 69 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.77LOEUF
pLI 0.000
Z-score 2.41
OE 0.47 (0.29–0.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.27Z-score
OE missense 0.74 (0.65–0.85)
145 obs / 194.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.47 (0.29–0.77)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.65–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
0≤1.21.6
LoF obs/exp: 11 / 23.6Missense obs/exp: 145 / 194.8Syn Z: -0.30

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
DMC1 and RAD51 bind FxxA and FxPP motifs of BRCA2 via two separate interfaces.
Miron S et al.·Nucleic Acids Res
2024
In vivo versus in silico assessment of potentially pathogenic missense variants in human reproductive genes.
Ding X et al.·Proc Natl Acad Sci U S A
2023
Identification of missense DMC1 variants in males with non-obstructive azoospermia.
Ullah N et al.·J Assist Reprod Genet
2025
Compound heterozygous DMC1 variants cause non-obstructive azoospermia by defective replication protein A replacement.
Wang Y et al.·Reprod Biomed Online
2025
Meiosis interrupted: the genetics of female infertility via meiotic failure.
Biswas L et al.·Reproduction
2021Review
Role of recA/RAD51 family proteins in mammals.
Kawabata M et al.·Acta Med Okayama
2005Review
Homologous Recombination Deficiency: Cancer Predispositions and Treatment Implications.
Toh M et al.·Oncologist
2021Review
A variant in RNF212B may contribute to female infertility and recurrent pregnancy loss.
Darko ME et al.·HGG Adv
2025Case report
A pathogenic DMC1 frameshift mutation causes nonobstructive azoospermia but not primary ovarian insufficiency in humans.
Cao D et al.·Mol Hum Reprod
2021Case report
[Human infertility: meiotic genes as potential candidates].
Mandon-Pépin B et al.·Gynecol Obstet Fertil
2002Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools