MCM7

Chr 7

minichromosome maintenance complex component 7

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

The MCM7 protein functions as a core component of the MCM2-7 replicative helicase complex that is essential for DNA replication initiation and elongation in eukaryotic cells. Mutations cause autosomal recessive primordial dwarfism with severe growth retardation and microcephaly, typically presenting from birth. This gene shows minimal tolerance to loss-of-function variants, reflecting its critical role in fundamental cellular processes.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.28
Clinical SummaryMCM7
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
14 unique Pathogenic / Likely Pathogenic· 69 VUS of 123 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.28LOEUF
pLI 0.000
Z-score 0.16
OE 0.97 (0.751.28)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.72Z-score
OE missense 1.10 (1.021.18)
498 obs / 454.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.97 (0.751.28)
00.351.4
Missense OE1.10 (1.021.18)
00.61.4
Synonymous OE1.34
01.21.6
LoF obs/exp: 37 / 38.1Missense obs/exp: 498 / 454.6Syn Z: -3.41
DN
0.6357th %ile
GOF
0.3987th %ile
LOF
0.4726th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

123 submitted variants in ClinVar

Classification Summary

Pathogenic14
VUS69
Likely Benign5
Benign5
Conflicting1
14
Pathogenic
69
VUS
5
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
0
0
0
VUS
1
66
2
0
69
Likely Benign
0
3
1
1
5
Benign
0
1
0
4
5
Conflicting
1
Total17017594

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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