MCM3
protein-codingminichromosome maintenance complex component 3, the group of minichromosome maintenance 2-7 complex|MCM family
Gene summary
The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are involved in the initiation of eukaryotic genome replication. The hexameric protein complex formed by 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. This protein is a subunit of the protein complex that consists of MCM2-7. It has been shown to interact directly with MCM5/CDC46. This protein also interacts with and is acetylated by MCM3AP, a chromatin-associated acetyltransferase. The acetylation of this protein inhibits the initiation of DNA replication and cell cycle progression. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2018]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~20.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MCM3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002388.6. 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 | 2 | 2 | ||||
| missense | 126 | 2 | 128 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 133 | 2 | 0 | 135 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002379.4 | 17 | MANE Select | |
| Ensembl | ENSP00000472940.2 | 17 | MANE Select | |
| RefSeq | NP_001257401.2 | 16 | Standard | |
| RefSeq | NP_001353298.1 | 18 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| mcm3 | Danio rerio | Structure: head Quality: decreased size 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
- Retinoblastoma (RB) in Cancer
- G1 to S cell cycle control
Biological Process
- G1/S transition of mitotic cell cycle
- DNA replication
- DNA replication initiation
Molecular Function
- DNA binding
- helicase activity
- protein binding
- ATP binding
Cellular Component
- nuclear chromosome, telomeric region
- nucleus
- nucleoplasm
- alpha DNA polymerase:primase complex
- nucleolus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000596288
- Coding exons
- 17
- Length
- 20873
- Individuals with no LoFs
- 125646
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 102
- Defined
- 125748
- p
- 0.000406
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.805 | 453 | 504 | 0.899 | 0.0000292 | 5568 |
| Missense (PolyPhen) | 107 | 153.85 | 0.69547 | 1576 | ||
| Synonymous | -0.0677 | 187 | 186 | 1.01 | 0.00000998 | 1674 |
| Loss of Function | 2.88 | 24 | 44.8 | 0.535 | 0.00000276 | 491 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00062 | 0.00062 | rare |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00040 | 0.00040 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00030 | 0.00030 | rare |
| South Asian | 0.0014 | 0.0014 | notable |
| Other | 0.00049 | 0.00049 | 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 DNA replication and cell proliferation.;
Recessive Scores
- pRec
- 0.275
Intolerance Scores
- RVIS EVS
- -0.93
- RVIS percentile EVS
- 9.68
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.911
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |