MCM7

Chr 7

minichromosome maintenance complex component 7

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

NCBI Gene: 4176 ENSG00000166508 UniProt: P33993 OMIM: 600592

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.28

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.72Z-score

OE missense 1.10 (1.02–1.18)

498 obs / 454.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.97 (0.75–1.28)

0≤0.351.4

Missense OE?1.10 (1.02–1.18)

0≤0.61.4

Synonymous OE?1.34

0≤1.21.6

LoF obs/exp: 37 / 38.1Missense obs/exp: 498 / 454.6Syn Z: -3.41

Background carrier burden — how many people carry a rare variant somewhere in MCM7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 48

1,133 rare PASS variants

Rare truncating (LoF)

1 in 690

214 rare PASS variants

Rare synonymous (reference)

1 in 93

494 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MCM7. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 70	1 in 780
South Asian	~43k	1 in 51	1 in 390
Remaining (unassigned)	~30k	1 in 42	1 in 550
European (Finnish)	~27k	1 in 130	1 in 1,800
Admixed American	~22k	1 in 47	1 in 770
African / African American	~21k	1 in 48	1 in 860
East Asian	~20k	1 in 60	1 in 2,200
Ashkenazi Jewish	~13k	1 in 170	≈ 1 in 3,200
Middle Eastern	~2,884	1 in 51	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 15 coding exons well covered in gnomAD exomes and genomes.? see exons ↓