MCM4 Gene - Minichromosome Maintenance Complex Component 4
Essential regulator of DNA replication initiation and genome stability
Gene Information Card
| Symbol | MCM4 |
|---|---|
| Full Name | Minichromosome Maintenance Complex Component 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q11.21 |
| NCBI Gene ID | 4173 ncbi.nlm.nih.gov/gene/4173 |
| Ensembl ID | ENSG00000104738 |
| UniProt ID | P33991 |
| OMIM ID | 602638 |
| HGNC ID | 6947 |
| Aliases | CDC21, CDC54, hCdc21, MCM4 |
Description
MCM4 encodes a component of the MCM2-7 hexameric complex, which functions as the replicative helicase essential for DNA replication initiation and elongation. The protein is a key regulator of cell cycle progression and genome stability. Mutations in MCM4 are associated with primordial dwarfism and natural killer cell deficiency, and the gene is implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primordial dwarfism with immunodeficiency (MCM4 deficiency) | Loss-of-function mutations impair MCM complex assembly and DNA replication, leading to growth retardation and immune defects | OMIM #609981; ClinVar |
| Natural killer cell deficiency | MCM4 mutations disrupt NK cell proliferation and maturation | OMIM #609981; PubMed |
| Breast cancer | Altered MCM4 expression and copy number changes contribute to genomic instability | COSMIC; PubMed |
| Colorectal cancer | MCM4 overexpression associated with poor prognosis and replication stress | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 38.5 | High |
| Bone marrow | 25.3 | High |
| Lymph node | 22.1 | High |
| Brain | 8.2 | Low |
| Heart | 6.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 45.2 | Cervical cancer cell line |
| K562 | 38.9 | Leukemia cell line |
| A549 | 30.1 | Lung cancer cell line |
| MCF7 | 28.4 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.71dupG (p.Pro25Alafs*20) | Frameshift | Rare | Loss of function; associated with primordial dwarfism |
| c.1742G>A (p.Arg581His) | Missense | 0.001% | Impaired helicase activity |
| c.2074C>T (p.Arg692Trp) | Missense | 0.002% | Reduced MCM complex stability |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or disrupt helicase activity, leading to replication stress and growth defects.
Gain of Function (GOF)
Not well documented; some missense variants may increase helicase activity but evidence is limited.
Dominant Negative (DN)
Missense mutations that impair complex assembly and function in a dominant manner, as seen in some MCM4-related disorders.
View complete mutation data：
Gene Ontology (GO)
| • DNA helicase activity | • DNA replication initiation |
| • MCM complex | • cell cycle |
| • chromatin binding | • nucleus |
Pathways
• DNA replication (Reactome: R-HSA-69306)
• Cell cycle (KEGG: hsa04110)
• MCM complex assembly (Reactome: R-HSA-68962)
Protein Summary
MCM4 is a 863-amino acid protein that forms part of the MCM2-7 hexameric helicase complex. It contains an AAA+ ATPase domain essential for DNA unwinding during replication. The protein is regulated by phosphorylation and interacts with other MCM subunits and cell cycle regulators. Its expression is cell cycle-dependent, peaking in S phase.
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