MCM5

Chr 22AR

minichromosome maintenance complex component 5

NCBI Gene: 4174ENSG00000100297UniProt: P33992

Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells (PubMed:40940420). Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:16899510, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425)

Primary Disease Associations & Inheritance

?Meier-Gorlin syndrome 8MIM #617564
AR
503
ClinVar variants
3
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MCM5
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.
📋
ClinVar Variants
3 Pathogenic / Likely Pathogenic· 221 VUS of 503 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.56LOEUF
pLI 0.001
Z-score 3.56
OE 0.35 (0.22–0.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.16Z-score
OE missense 0.85 (0.78–0.92)
409 obs / 480.6 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.0.35 (0.22–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.78–0.92)
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.1.07
0≤1.21.6
LoF obs/exp: 12 / 34.6Missense obs/exp: 409 / 480.6Syn Z: -0.74

ClinVar Variant Classifications

503 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3
VUS221
Likely Benign147
Benign16
Conflicting1
3
Pathogenic
221
VUS
147
Likely Benign
16
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
3
0
3
Likely Pathogenic
0
0
0
0
0
VUS
4
199
18
0
221
Likely Benign
0
6
56
85
147
Benign
0
3
4
9
16
Conflicting
—1
Total42088194388

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

View in ClinVar →

Protein Context — Lollipop Plot

MCM5 · 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

?Meier-Gorlin syndrome 8

MIM #617564

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
O-GlcNAcylation of YTHDF2 promotes HBV-related hepatocellular carcinoma progression in an N(6)-methyladenosine-dependent manner.
Yang Y et al.·Signal Transduct Target Ther
2023
m(6) A-Dependent Modulation via IGF2BP3/MCM5/Notch Axis Promotes Partial EMT and LUAD Metastasis.
Yang X et al.·Adv Sci (Weinh)
2023
Enhanced MCM5 Level Predicts Bad Prognosis in Acute Myeloid Leukemia.
Wang S et al.·Mol Biotechnol
2023
Proteomic profiling identifies miR-423-5p as a modulator of oncogenic metabolism in HCC.
Luce A et al.·J Transl Med
2025
MCM5 promotes tumour proliferation and correlates with the progression and prognosis of renal cell carcinoma.
Gong B et al.·Int Urol Nephrol
2019
MCM5 is an oncogene of colon adenocarcinoma and promotes progression through cell cycle control.
Mao J et al.·Acta Histochem
2023
TFAP4 Regulation of MCM5 Activates the PI3K/AKT Pathway to Promote Invasion and Metastasis of Gastric Cancer.
Yuan YW et al.·Dig Dis Sci
2025
The role of MCM5 expression in cervical cancer: Correlation with progression and prognosis.
Wang D et al.·Biomed Pharmacother
2018
Detection of MCM5 as a novel non-invasive aid for the diagnosis of endometrial and ovarian tumours.
Stockley J et al.·BMC Cancer
2020
Biallelic GINS2 variant p.(Arg114Leu) causes Meier-Gorlin syndrome with craniosynostosis.
Nabais Sá MJ et al.·J Med Genet
2022
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