MCM9

Chr 6AR

minichromosome maintenance 9 homologous recombination repair factor

Also known as: C6orf61, MCMDC1, ODG4, dJ329L24.1, dJ329L24.3

NCBI Gene: 254394ENSG00000111877UniProt: Q9NXL9

The protein encoded by this gene is a member of the mini-chromosome maintenance (MCM) protein family that are essential for the initiation of eukaryotic genome replication. Binding of this protein to chromatin has been shown to be a pre-requisite for recruiting the MCM2-7 helicase to DNA replication origins. This protein also binds, and is a positive regulator of, the chromatin licensing and DNA replication factor 1, CDT1. [provided by RefSeq, Nov 2010]

Primary Disease Associations & Inheritance

Ovarian dysgenesis 4MIM #616185
AR
244
ClinVar variants
35
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MCM9
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
35 Pathogenic / Likely Pathogenic· 168 VUS of 244 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.
0.87LOEUF
pLI 0.000
Z-score 2.24
OE 0.64 (0.47–0.87)
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.
1.45Z-score
OE missense 0.83 (0.77–0.90)
493 obs / 592.5 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.0.64 (0.47–0.87)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.77–0.90)
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.0.94
0≤1.21.6
LoF obs/exp: 28 / 44.0Missense obs/exp: 493 / 592.5Syn Z: 0.73

ClinVar Variant Classifications

244 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic12
VUS168
Likely Benign27
Benign11
Conflicting3
23
Pathogenic
12
Likely Pathogenic
168
VUS
27
Likely Benign
11
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
21
0
23
Likely Pathogenic
3
0
9
0
12
VUS
1
160
6
1
168
Likely Benign
0
19
0
8
27
Benign
0
7
0
4
11
Conflicting
—3
Total61863613244

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

View in ClinVar →

Protein Context — Lollipop Plot

MCM9 · 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

Ovarian dysgenesis 4

MIM #616185

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical syndromes linked to biallelic germline variants in MCM8 and MCM9.
Helderman NC et al.·HGG Adv
2025
MCM8-mediated mitophagy protects vascular health in response to nitric oxide signaling in a mouse model of Kawasaki disease.
Lin M et al.·Nat Cardiovasc Res
2023Functional
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
MCM8 and MCM9 Nucleotide Variants in Women With Primary Ovarian Insufficiency.
Desai S et al.·J Clin Endocrinol Metab
2017
Pathogenic germline MCM9 variants are rare in Australian Lynch-like syndrome patients.
Liu Q et al.·Cancer Genet
2016Cohort
Novel pathogenic mutations in minichromosome maintenance complex component 9 (MCM9) responsible for premature ovarian insufficiency.
Guo T et al.·Fertil Steril
2020
Meiosis interrupted: the genetics of female infertility via meiotic failure.
Biswas L et al.·Reproduction
2021Review
A non-sense MCM9 mutation in a familial case of primary ovarian insufficiency.
Fauchereau F et al.·Clin Genet
2016
MCM9 mutations are associated with ovarian failure, short stature, and chromosomal instability.
Wood-Trageser MA et al.·Am J Hum Genet
2014
Genetic variants in diminished ovarian reserve and premature ovarian insufficiency: implications for assisted reproductive outcomes.
Xu Q et al.·J Assist Reprod Genet
2025
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