DMC1

Chr 22

DNA meiotic recombinase 1

Also known as: DMC1H, LIM15, dJ199H16.1

NCBI Gene: 11144 ENSG00000100206 UniProt: Q8IV36 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.77

Clinical Summary— DMC1

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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

5 unique Pathogenic / Likely Pathogenic· 30 VUS of 44 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 OE?0.47 (0.29–0.77)

0≤0.351.4

Missense OE?0.74 (0.65–0.85)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 11 / 23.6Missense obs/exp: 145 / 194.8Syn Z: -0.30

This gene — mechanism propensity

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

44 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic3

VUS30

Likely Benign1

Benign1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	2	0	2
Likely Pathogenic	3	0	3
VUS	30	0	30
Likely Benign	0	1	1
Benign	1	0	1
Total	36	1	37

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap DMC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →