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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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DMC1
DNA meiotic recombinase 1
Chromosome 22 Β· 22q13.1
NCBI Gene: 11144Ensembl: ENSG00000100206.12HGNC: HGNC:2927UniProt: Q14565
70PubMed Papers
20Diseases
0Drugs
5Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
DNA strand exchange activitysingle-stranded DNA bindingprotein bindingATP-dependent activity, acting on DNAazoospermiaCryptozoospermiapartial chromosome Y deletionspermatogenic failure 57
✦AI Summary

DMC1 (DNA meiotic recombinase 1) is a strand exchange recombinase essential for meiotic homologous recombination 1. DMC1 catalyzes pairing and shuffling of homologous DNA sequences by assembling into nucleoprotein filaments on single-stranded DNA, facilitating homologous strand assimilation and resolution of meiotic double-strand breaks 12. The protein functions through distinct molecular interfaces: it binds BRCA2's P-motifs (PhePP) via a conserved phenylalanine, which stabilizes DMC1 nucleoprotein filaments and increases strand invasion efficiency 3. DMC1 recruitment to meiotic double-strand break sites is facilitated by RNase H1-mediated degradation of DNA-RNA hybrids and is negatively regulated by the FIGNL1-FIRRM complex to prevent aberrant loading on intact chr22 45. Histone lactylation associates with DMC1 at recombination hotspots, linking metabolic signaling to meiotic gene expression 6. Clinically, DMC1 mutations cause primary ovarian insufficiency in women 7 and non-obstructive azoospermia in men 8, with all individuals harboring meiotic gene defects showing unsuccessful sperm retrieval, indicating diagnostic value for predicting treatment outcomes 8.

Sources cited
1
DMC1 is a recombinase that catalyzes pairing and shuffling of homologous DNA sequences via presynaptic filament formation on ssDNA
PMID: 18275380
2
DMC1 is an essential recombinase for meiotic homologous recombination and ensures faithful chromosome segregation
PMID: 35729697
3
DMC1 binds BRCA2's P-motifs through a distinct interface, and this interaction stabilizes DMC1 nucleoprotein filaments
PMID: 38828772
4
RNase H1 facilitates DMC1 recruitment to meiotic double-strand breaks by degrading DNA-RNA hybrids
PMID: 37378420
5
FIGNL1-FIRRM complex negatively regulates DMC1 accumulation on chromatin to promote efficient strand invasion
PMID: 39147779
6
Histone H4K8 lactylation associates with DMC1 at meiotic recombination hotspots and links metabolic signaling to meiotic function
PMID: 39928879
7
DMC1 mutations are associated with primary ovarian insufficiency in women
PMID: 34794894
8
DMC1 mutations cause non-obstructive azoospermia in men; genetic diagnosis predicts unsuccessful sperm retrieval
PMID: 35172124
Disease Associationsβ“˜20
azoospermiaOpen Targets
0.50Moderate
CryptozoospermiaOpen Targets
0.11Weak
partial chromosome Y deletionOpen Targets
0.10Suggestive
spermatogenic failure 57Open Targets
0.09Suggestive
spermatogenic failure 50Open Targets
0.09Suggestive
spermatogenic failure 25Open Targets
0.09Suggestive
spermatogenic failure 71Open Targets
0.09Suggestive
spermatogenic failure 59Open Targets
0.09Suggestive
spermatogenic failure 60Open Targets
0.09Suggestive
spermatogenic failure 73Open Targets
0.09Suggestive
spermatogenic failure 74Open Targets
0.09Suggestive
spermatogenic failure 61Open Targets
0.09Suggestive
spermatogenic failure 62Open Targets
0.09Suggestive
spermatogenic failure 88Open Targets
0.09Suggestive
spermatogenic failure 48Open Targets
0.09Suggestive
spermatogenic failure, X-linked, 2Open Targets
0.09Suggestive
spermatogenic failure 63Open Targets
0.09Suggestive
isochromosomy YpOpen Targets
0.09Suggestive
spermatogenic failure 12Open Targets
0.08Suggestive
spermatogenic failure 1Open Targets
0.08Suggestive
Pathogenic Variants5
NM_007068.4(DMC1):c.164C>T (p.Thr55Ile)Likely pathogenic
Non-obstructive azoospermia
β˜†β˜†β˜†β˜†2025β†’ Residue 55
NM_007068.4(DMC1):c.490A>G (p.Thr164Ala)Likely pathogenic
Non-obstructive azoospermia
β˜†β˜†β˜†β˜†2025β†’ Residue 164
NM_007068.4(DMC1):c.581A>G (p.Tyr194Cys)Likely pathogenic
Non-obstructive azoospermia
β˜†β˜†β˜†β˜†2025β†’ Residue 194
NM_007068.4(DMC1):c.364A>G (p.Thr122Ala)Pathogenic
Azoospermia
β˜†β˜†β˜†β˜†2021β†’ Residue 122
NM_007068.4(DMC1):c.860C>A (p.Pro287His)Pathogenic
Azoospermia
β˜†β˜†β˜†β˜†2021β†’ Residue 287
View on ClinVar β†—
Related Genes
BRCA2Protein interaction98%ATMProtein interaction87%MSH4Protein interaction86%BRCA1Protein interaction83%CDK4Protein interaction83%RPA1Protein interaction79%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
98%
Heart
42%
Ovary
27%
Lung
20%
Liver
10%
Gene Interaction Network
Click a node to explore
DMC1BRCA2ATMMSH4BRCA1CDK4RPA1
PROTEIN STRUCTURE
Preparing viewer…
PDB6R3P Β· 2.05 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.99LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.67 [0.47–0.99]
RankingsWhere DMC1 stands among ~20K protein-coding genes
  • #6,708of 20,598
    Most Researched70
  • #3,551of 5,498
    Most Pathogenic Variants5
  • #9,502of 17,882
    Most Constrained (LOEUF)0.99
Genes detectedDMC1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Mechanism of eukaryotic homologous recombination.
PMID: 18275380
Annu Rev Biochem Β· 2008
1.00
2
Genetics of ovarian insufficiency and defects of folliculogenesis.
PMID: 34794894
Best Pract Res Clin Endocrinol Metab Β· 2022
0.90
3
Whole-exome sequencing improves the diagnosis and care of men with non-obstructive azoospermia.
PMID: 35172124
Am J Hum Genet Β· 2022
0.80
4
DMC1 and RAD51 bind FxxA and FxPP motifs of BRCA2 via two separate interfaces.
PMID: 38828772
Nucleic Acids Res Β· 2024
0.70
5
FIGNL1-FIRRM is essential for meiotic recombination and prevents DNA damage-independent RAD51 and DMC1 loading.
PMID: 39147779
Nat Commun Β· 2024
0.60