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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
MCM8
minichromosome maintenance 8 homologous recombination repair factor
Chromosome 20 Β· 20p12.3
NCBI Gene: 84515Ensembl: ENSG00000125885.14HGNC: HGNC:16147UniProt: B4DN82
86PubMed Papers
21Diseases
0Drugs
14Pathogenic Variants
FUNCTIONAL ROLE
DNA RepairHomologous Recombination
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
DNA replicationenzyme bindingMutLbeta complex bindingMutSalpha complex bindingprimary ovarian insufficiencyuterine fibroidUterine leiomyomamenopause
✦AI Summary

MCM8 is a DNA helicase component of the MCM8-MCM9 complex essential for homologous recombination repair of double-stranded breaks and interstrand crosslinks 1. The complex functions as a 3'-5' DNA helicase with ssDNA-stimulated ATPase activity 2 and promotes DNA resection by recruiting and activating the MRE11-RAD50-NBN complex to damage sites 3. MCM8 indirectly regulates RAD51 localization to DNA lesions 1 and facilitates mitochondrial DNA recombination 4. The complex is dispensable for S-phase DNA replication but plays critical roles in gametogenesis through homologous recombination regulation 1. MCM8 mutations are the predominant genetic cause of primary ovarian insufficiency/premature ovarian failure 567, where it recruits R-loop-resolving helicases DDX5 and DHX9 to prevent genome instability in primordial germ cells 8. MCM8 deficiency impairs germ cell proliferation and fertility 8. In non-obstructive azoospermia, MCM8 mutations correlate with failed sperm retrieval 9. Beyond reproduction, MCM8 regulates mitophagy through LC3 recruitment, protecting vascular health in Kawasaki disease models 10, and is upregulated in colorectal cancer where it promotes tumor progression 11.

Sources cited
1
MCM8-MCM9 complex function in DSB and ICL repair, RAD51 regulation, and stabilization of MCM9
PMID: 23401855
2
MCM8-MCM9 complex as 3'-5' DNA helicase with ssDNA-stimulated ATPase activity
PMID: 37309874
3
MCM8 recruits MRN complex and promotes its nuclease activity for DNA resection
PMID: 26215093
4
MCM8 facilitates somatic mitochondrial DNA recombination
PMID: 36355348
5
MCM8 interacts with DDX5 for R-loop resolution and is essential for primordial germ cell development
PMID: 38858601
6
MCM8 mutations identified through exome sequencing in primary ovarian insufficiency cases
PMID: 26243799
7
MCM8 associated with nonsyndromic primary ovarian insufficiency through meiosis/DNA repair pathways
PMID: 34794894
8
MCM8/9 mutations correlate with primary ovarian failure/insufficiency and infertility with meiotic defects
PMID: 30743181
9
MCM8 mutations identified in non-obstructive azoospermia correlating with failed sperm retrieval
PMID: 35172124
10
MCM8 regulates mitophagy via LC3 recruitment and protects vascular health in Kawasaki disease
PMID: 39195969
11
MCM8 is upregulated in colorectal cancer and promotes tumor progression through CHSY1 regulation
PMID: 37710286
Disease Associationsβ“˜21
primary ovarian insufficiencyOpen Targets
0.68Moderate
uterine fibroidOpen Targets
0.52Moderate
Uterine leiomyomaOpen Targets
0.47Moderate
menopauseOpen Targets
0.44Moderate
MenorrhagiaOpen Targets
0.43Moderate
azoospermiaOpen Targets
0.35Weak
breast carcinomaOpen Targets
0.35Weak
Raynaud diseaseOpen Targets
0.35Weak
ovulationOpen Targets
0.35Weak
estrogen-receptor negative breast cancerOpen Targets
0.34Weak
estrogen-receptor positive breast cancerOpen Targets
0.34Weak
Joubert syndrome 6Open Targets
0.34Weak
neurodegenerative diseaseOpen Targets
0.29Weak
respiratory tract infectious disorderOpen Targets
0.27Weak
ovarian dysfunctionOpen Targets
0.25Weak
genetic disorderOpen Targets
0.19Weak
cancerOpen Targets
0.10Weak
neoplasmOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
gastric cancerOpen Targets
0.09Suggestive
Premature ovarian failure 10UniProt
Pathogenic Variants14
NM_032485.6(MCM8):c.351_354del (p.Lys118fs)Pathogenic
not provided|Premature ovarian failure 10
β˜…β˜…β˜†β˜†2024β†’ Residue 118
NM_032485.6(MCM8):c.1866_1867del (p.Ala623fs)Pathogenic
Joubert syndrome 6
β˜…β˜†β˜†β˜†2025β†’ Residue 623
NM_032485.6(MCM8):c.1404C>A (p.Cys468Ter)Likely pathogenic
Premature ovarian failure 10
β˜…β˜†β˜†β˜†2023β†’ Residue 468
NM_032485.6(MCM8):c.1735dup (p.Met579fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 579
NM_032485.6(MCM8):c.790-2A>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2022
NM_032485.6(MCM8):c.1734-2A>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2022
NM_032485.6(MCM8):c.925C>T (p.Arg309Ter)Pathogenic
Premature ovarian failure 10
β˜…β˜†β˜†β˜†2019β†’ Residue 309
NM_032485.6(MCM8):c.278_281del (p.Ile93fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2016β†’ Residue 93
NM_032485.6(MCM8):c.482A>C (p.His161Pro)Likely pathogenic
Azoospermia|Premature ovarian failure 10
β˜…β˜†β˜†β˜†β†’ Residue 161
NM_032485.6(MCM8):c.1953+1G>CLikely pathogenic
Premature ovarian failure 10
β˜†β˜†β˜†β˜†2021
NM_032485.6(MCM8):c.1470_1471insTA (p.Leu491fs)Pathogenic
Premature ovarian failure 10
β˜†β˜†β˜†β˜†2015β†’ Residue 491
NM_032485.6(MCM8):c.1954-1G>APathogenic
Premature ovarian failure 10
β˜†β˜†β˜†β˜†2015
NM_032485.6(MCM8):c.446C>G (p.Pro149Arg)Pathogenic
not provided|Premature ovarian failure 10
β˜†β˜†β˜†β˜†2014β†’ Residue 149
NM_032485.6(MCM8):c.2059C>T (p.Arg687Ter)Pathogenic
Premature ovarian failure 10
β˜†β˜†β˜†β˜†β†’ Residue 687
View on ClinVar β†—
Related Genes
MCMBPProtein interaction100%TIMELESSProtein interaction100%CDC6Protein interaction99%MCM2Protein interaction99%MCM3Protein interaction99%MCM4Protein interaction99%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
50%
Brain
38%
Lung
33%
Ovary
32%
Liver
21%
Gene Interaction Network
Click a node to explore
MCM8MCMBPTIMELESSCDC6MCM2MCM3MCM4
PROTEIN STRUCTURE
Preparing viewer…
PDB6L0O Β· 1.21 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.97LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.79 [0.65–0.97]
RankingsWhere MCM8 stands among ~20K protein-coding genes
  • #5,549of 20,598
    Most Researched86
  • #2,511of 5,498
    Most Pathogenic Variants14
  • #9,201of 17,882
    Most Constrained (LOEUF)0.97
Genes detectedMCM8
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
MCM8 interacts with DDX5 to promote R-loop resolution.
PMID: 38858601
EMBO J Β· 2024
1.00
2
Genetics of primary ovarian insufficiency: new developments and opportunities.
PMID: 26243799
Hum Reprod Update Β· 2015
0.90
3
Genetics of ovarian insufficiency and defects of folliculogenesis.
PMID: 34794894
Best Pract Res Clin Endocrinol Metab Β· 2022
0.80
4
MCM8-mediated mitophagy protects vascular health in response to nitric oxide signaling in a mouse model of Kawasaki disease.
PMID: 39195969
Nat Cardiovasc Res Β· 2023
0.70
5
Whole-exome sequencing improves the diagnosis and care of men with non-obstructive azoospermia.
PMID: 35172124
Am J Hum Genet Β· 2022
0.60