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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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MCM9
minichromosome maintenance 9 homologous recombination repair factor
Chromosome 6 Β· 6q22.31
NCBI Gene: 254394Ensembl: ENSG00000111877.19HGNC: HGNC:21484UniProt: A0A0S2Z662
48PubMed Papers
21Diseases
0Drugs
10Pathogenic Variants
FUNCTIONAL ROLE
DNA RepairHomologous Recombination
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
DNA replicationMutSbeta complex binding3'-5' DNA helicase activityprotein-containing complex binding46,XX gonadal dysgenesisneurodegenerative diseasepremature ovarian failure 1mathematical ability
✦AI Summary

MCM9 (minichromosome maintenance 9 homologous recombination repair factor) functions as a critical component of DNA repair mechanisms and reproductive biology. MCM9 forms a heterodimeric complex with MCM8 that acts as a 3'-5' DNA helicase essential for repairing double-strand breaks and DNA interstrand cross-links through homologous recombination 1. The MCM8-MCM9 complex also plays a crucial role in DNA mismatch repair by unwinding mismatch-containing DNA strands and recruiting MLH1 to chr6 2. During gametogenesis, MCM9 is predominantly expressed in spermatogonial stem cells and spermatogonia, where it maintains genomic integrity through both homologous recombination and mismatch repair pathways 2. Loss-of-function mutations in MCM9 cause primary ovarian insufficiency (POI) in females, characterized by premature ovarian failure before age 40 34. In males, MCM9 deficiency leads to non-obstructive azoospermia and Sertoli cell-only syndrome due to impaired DNA damage repair during spermatogenesis 2. Beyond reproductive disorders, biallelic MCM9 variants are associated with increased cancer risk, particularly colonic polyps, gastric cancer, and early-onset colorectal cancer 5. MCM9 also functions in mitophagy regulation, protecting vascular health by promoting mitochondrial quality control in response to nitric oxide signaling 6.

Sources cited
1
MCM9 forms a heterodimeric complex with MCM8 that acts as a 3'-5' DNA helicase for DNA repair
PMID: 38678026
2
MCM9 functions in DNA mismatch repair, interacts with MSH2 and MLH1, and is expressed in spermatogonial stem cells
PMID: 40593474
3
Loss-of-function mutations in MCM9 cause primary ovarian insufficiency
PMID: 27802094
4
MCM9 is associated with primary ovarian insufficiency characterized by premature ovarian failure
PMID: 26243799
5
Biallelic MCM9 variants are associated with colonic polyps, gastric cancer, and early-onset colorectal cancer
PMID: 40684266
6
MCM9 functions in mitophagy regulation and protects vascular health in response to nitric oxide signaling
PMID: 39195969
Disease Associationsβ“˜21
46,XX gonadal dysgenesisOpen Targets
0.69Moderate
neurodegenerative diseaseOpen Targets
0.52Moderate
premature ovarian failure 1Open Targets
0.42Moderate
mathematical abilityOpen Targets
0.36Weak
ovarian dysfunctionOpen Targets
0.30Weak
azoospermiaOpen Targets
0.29Weak
tooth diseaseOpen Targets
0.25Weak
actinic keratosisOpen Targets
0.23Weak
Abruptio PlacentaeOpen Targets
0.23Weak
male reproductive organ cancerOpen Targets
0.22Weak
cardiomyopathyOpen Targets
0.21Weak
genetic disorderOpen Targets
0.19Weak
schizophreniaOpen Targets
0.14Weak
intelligenceOpen Targets
0.12Weak
Premature ovarian insufficiencyOpen Targets
0.12Weak
partial chromosome Y deletionOpen Targets
0.07Suggestive
Hereditary breast and ovarian cancer syndromeOpen Targets
0.07Suggestive
spermatogenic failure 25Open Targets
0.07Suggestive
ring chromosome YOpen Targets
0.07Suggestive
spermatogenic failure 63Open Targets
0.07Suggestive
Ovarian dysgenesis 4UniProt
Pathogenic Variants10
NM_017696.3(MCM9):c.394C>T (p.Arg132Ter)Pathogenic
Premature ovarian failure 1|46,XX ovarian dysgenesis-short stature syndrome|Non-obstructive azoospermia
β˜…β˜…β˜†β˜†2023β†’ Residue 132
NM_017696.3(MCM9):c.1151-1G>APathogenic
46,XX ovarian dysgenesis-short stature syndrome
β˜…β˜…β˜†β˜†2022
NM_017696.3(MCM9):c.754C>T (p.Gln252Ter)Likely pathogenic
46,XX ovarian dysgenesis-short stature syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 252
NM_017696.3(MCM9):c.672_673delinsC (p.Glu225fs)Pathogenic
46,XX ovarian dysgenesis-short stature syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 225
NM_017696.3(MCM9):c.1732+2T>CPathogenic
Premature ovarian failure 1|46,XX ovarian dysgenesis-short stature syndrome
β˜…β˜†β˜†β˜†2024
NM_017696.3(MCM9):c.1529-7C>GLikely pathogenic
46,XX ovarian dysgenesis-short stature syndrome
β˜…β˜†β˜†β˜†2023
NM_017696.3(MCM9):c.1556G>A (p.Trp519Ter)Likely pathogenic
46,XX ovarian dysgenesis-short stature syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 519
NM_017696.3(MCM9):c.139_140del (p.Leu47fs)Likely pathogenic
46,XX ovarian dysgenesis-short stature syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 47
NM_017696.3(MCM9):c.1483G>T (p.Glu495Ter)Pathogenic
46,XX ovarian dysgenesis-short stature syndrome
β˜†β˜†β˜†β˜†2022β†’ Residue 495
NM_017696.3(MCM9):c.304+1G>ALikely pathogenic
not provided
β˜†β˜†β˜†β˜†2022
View on ClinVar β†—
Related Genes
RFC4Protein interaction100%PCNAProtein interaction100%MCM2Protein interaction100%POLEProtein interaction100%TIMELESSProtein interaction100%TIPINProtein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
31%
Liver
29%
Ovary
28%
Brain
23%
Heart
21%
Gene Interaction Network
Click a node to explore
MCM9RFC4PCNAMCM2POLETIMELESSTIPIN
PROTEIN STRUCTURE
Preparing viewer…
PDB7DPD Β· 2.55 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.92LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.73 [0.58–0.92]
RankingsWhere MCM9 stands among ~20K protein-coding genes
  • #9,096of 20,598
    Most Researched48
  • #2,877of 5,498
    Most Pathogenic Variants10
  • #8,383of 17,882
    Most Constrained (LOEUF)0.92
Genes detectedMCM9
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Genetics of primary ovarian insufficiency: new developments and opportunities.
PMID: 26243799
Hum Reprod Update Β· 2015
1.00
2
Genetics of ovarian insufficiency and defects of folliculogenesis.
PMID: 34794894
Best Pract Res Clin Endocrinol Metab Β· 2022
0.90
3
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
0.80
4
Mechanism of DNA unwinding by MCM8-9 in complex with HROB.
PMID: 38678026
Nat Commun Β· 2024
0.70
5
MCM9 deficiency impairs DNA damage repair during spermatogenesis, leading to Sertoli cell-only syndrome in humans.
PMID: 40593474
Cell Death Discov Β· 2025
0.60