MCM7
protein-codingminichromosome maintenance complex component 7, the group of minichromosome maintenance 2-7 complex|Protein phosphatase 1 regulatory subunits|MCM family|MicroRNA protein coding host genes
Gene summary
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]
- MCM2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0002254
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MCM7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005916.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 4 | 7 | ||
| missense | 2 | 149 | 5 | 1 | 157 | |
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 5 | 0 | 157 | 7 | 5 | 174 |
Highest pathogenic variant AF is 0.000032834207
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005907.3 | 15 | MANE Select | |
| Ensembl | ENSP00000307288.5 | 15 | MANE Select | |
| RefSeq | NP_001265524.1 | 11 | Standard | |
| RefSeq | NP_001426200.1 | 12 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| mcm7 | Danio rerio | Structure: anatomical system Quality: quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell cycle - Homo sapiens (human)
- DNA replication - Homo sapiens (human)
- Cell Cycle
- miRNA Regulation of DNA Damage Response
- Retinoblastoma (RB) in Cancer
Biological Process
- G1/S transition of mitotic cell cycle
- DNA replication
- DNA unwinding involved in DNA replication
- DNA replication initiation
- cellular response to DNA damage stimulus
Molecular Function
- DNA binding
- single-stranded DNA binding
- ATP-dependent DNA helicase activity
- protein binding
- ATP binding
Cellular Component
- nuclear chromosome, telomeric region
- chromatin
- nucleus
- nucleoplasm
- nucleolus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000303887
- Coding exons
- 15
- Length
- 9213
- Individuals with no LoFs
- 125597
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 151
- Defined
- 125748
- p
- 0.000601
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.723 | 498 | 455 | 1.10 | 0.0000301 | 4647 |
| Missense (PolyPhen) | 136 | 167.6 | 0.81144 | 1706 | ||
| Synonymous | -3.41 | 222 | 166 | 1.34 | 0.00000973 | 1465 |
| Loss of Function | 0.158 | 37 | 38.1 | 0.972 | 0.00000211 | 406 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00050 | 0.00049 | rare |
| Ashkenazi Jewish | 0.0022 | 0.0022 | notable |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00058 | 0.00058 | rare |
| South Asian | 0.00085 | 0.00085 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. 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. Required for S-phase checkpoint activation upon UV-induced damage. {ECO:0000269|PubMed:15210935, ECO:0000269|PubMed:15538388, ECO:0000269|PubMed:9305914}.;
Recessive Scores
- pRec
- 0.414
Intolerance Scores
- LoFtool
- 0.980
- RVIS EVS
- -1.26
- RVIS percentile EVS
- 5.31
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |