MCM7

Chr 7

minichromosome maintenance complex component 7

Also known as: CDC47, MCM2, P1.1-MCM3, P1CDC47, P85MCM, PNAS146, PPP1R104

NCBI Gene: 4176ENSG00000166508UniProt: P33993

The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by the MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 4 and 6 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. Cyclin D1-dependent kinase, CDK4, is found to associate with this protein, and may regulate the binding of this protein with the tumorsuppressor protein RB1/RB. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

191
ClinVar variants
26
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MCM7
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 152 VUS of 191 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.
1.28LOEUF
pLI 0.000
Z-score 0.16
OE 0.97 (0.75–1.28)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.72Z-score
OE missense 1.10 (1.02–1.18)
498 obs / 454.6 exp
Tolerant

Tolerant to missense variation

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.0.97 (0.75–1.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.10 (1.02–1.18)
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.1.34
0≤1.21.6
LoF obs/exp: 37 / 38.1Missense obs/exp: 498 / 454.6Syn Z: -3.41

ClinVar Variant Classifications

191 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic2
VUS152
Likely Benign6
Benign6
Conflicting1
24
Pathogenic
2
Likely Pathogenic
152
VUS
6
Likely Benign
6
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
22
0
24
Likely Pathogenic
0
0
2
0
2
VUS
1
144
7
0
152
Likely Benign
0
3
1
2
6
Benign
0
1
1
4
6
Conflicting
—1
Total1150336191

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

View in ClinVar →

Protein Context — Lollipop Plot

MCM7 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
DNA-dependent protein kinase regulates lysosomal AMP-dependent protein kinase activation and autophagy.
Puustinen P et al.·Autophagy
2020
Prognostic and Clinical Significance of the Proliferation Marker MCM7 in Breast Cancer.
Lashen AG et al.·Pathobiology
2025
Whole Genome Sequencing of "Mutation-Negative" Individuals With Cornelia de Lange Syndrome.
Ansari M et al.·Hum Mutat
2025
Proteomic profiling identifies miR-423-5p as a modulator of oncogenic metabolism in HCC.
Luce A et al.·J Transl Med
2025
Homozygous mutation in MCM7 causes autosomal recessive primary microcephaly and intellectual disability.
Ravindran E et al.·J Med Genet
2022
Single-cell atlas of the liver myeloid compartment before and after cure of chronic viral hepatitis.
Cui A et al.·J Hepatol
2024
Biomarkers for prognosis of meningioma patients: A systematic review and meta-analysis.
Aung TM et al.·PLoS One
2024Meta-analysis
MCM7 expression is a promising predictor of recurrence in patients surgically resected for meningiomas.
Winther TL et al.·J Neurooncol
2017Cohort
Gene profiling of high risk neuroblastoma.
Vasudevan SA et al.·World J Surg
2005Review
Immunohistochemical expression and prognostic significance of CCND3, MCM2 and MCM7 in Hodgkin lymhoma.
Marnerides A et al.·Anticancer Res
2011
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