MCM5 Gene - Minichromosome Maintenance Complex Component 5
Essential DNA replication licensing factor and potential cancer biomarker
Gene Information Card
| Symbol | MCM5 |
|---|---|
| Full Name | Minichromosome maintenance complex component 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q12.3 |
| NCBI Gene ID | 4174 ncbi.nlm.nih.gov/gene/4174 |
| Ensembl ID | ENSG00000100297 |
| UniProt ID | P33991 |
| OMIM ID | 602696 |
| HGNC ID | 6948 |
| Aliases | CDC46, P1-CDC46, MCM5_HUMAN |
Description
MCM5 encodes a member of the minichromosome maintenance (MCM) protein family, which is essential for DNA replication initiation and elongation. MCM5 is a component of the MCM2-7 hexameric complex that functions as a replicative helicase. It is regulated by cell cycle-dependent phosphorylation and is required for the licensing of replication origins. MCM5 expression is elevated in proliferating cells and is frequently upregulated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Meier-Gorlin syndrome 8 | Loss-of-function mutations in MCM5 impair DNA replication licensing, leading to primordial dwarfism and microcephaly. | OMIM #617053; PMID: 28575650 |
| Colorectal cancer | MCM5 overexpression correlates with tumor progression and poor prognosis. | PMID: 25964209 |
| Breast cancer | MCM5 upregulation is associated with aggressive subtypes and reduced survival. | PMID: 27381357 |
| Lung cancer | MCM5 is overexpressed in non-small cell lung cancer and promotes proliferation. | PMID: 29351285 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Bone marrow | 18.2 | High |
| Lymph node | 15.1 | High |
| Brain | 4.3 | Low |
| Heart | 3.8 | Low |
| Liver | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 32.4 | Cervical cancer cell line |
| A549 | 27.8 | Lung cancer cell line |
| MCF7 | 25.1 | Breast cancer cell line |
| HEK293 | 22.6 | Embryonic kidney cell line |
| K562 | 19.3 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.172C>T (p.Arg58Trp) | Missense | Rare | Loss of function; associated with Meier-Gorlin syndrome |
| c.1066G>A (p.Glu356Lys) | Missense | Rare | Unknown significance; reported in ClinVar |
| c.1327_1329del (p.Glu443del) | In-frame deletion | Rare | Likely pathogenic; disrupts MCM complex assembly |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of function; reported in Meier-Gorlin syndrome |
Mutation functional classification
Loss of Function (LOF)
Missense and start-loss mutations (e.g., p.Arg58Trp, p.Met1Val) impair helicase activity or complex formation, leading to replication licensing defects and Meier-Gorlin syndrome.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in MCM5. Overexpression in cancer is likely due to transcriptional upregulation rather than activating mutations.
Dominant Negative (DN)
Heterozygous mutations in MCM5 can exert dominant-negative effects by disrupting the MCM2-7 hexamer assembly, as observed in some Meier-Gorlin syndrome cases.
View complete mutation data：
Gene Ontology (GO)
| • DNA replication initiation (GO:0006270) | • DNA helicase activity (GO:0003678) |
| • MCM complex (GO:0042555) | • nucleus (GO:0005634) |
| • cell cycle (GO:0007049) | • chromatin binding (GO:0003682) |
Pathways
• Cell Cycle - DNA replication (KEGG hsa04110)
• MCM pathway (Reactome R-HSA-68962)
• Activation of the pre-replicative complex (Reactome R-HSA-68949)
• DNA replication (Reactome R-HSA-69306)
Protein Summary
MCM5 is a 734-amino acid protein (82 kDa) belonging to the AAA+ ATPase family. It forms a heterohexameric complex with MCM2, MCM3, MCM4, MCM6, and MCM7, which constitutes the replicative helicase essential for unwinding DNA during replication. MCM5 contains an N-terminal domain involved in chromatin binding and a C-terminal ATPase domain. Phosphorylation by CDK and DDK kinases regulates its loading onto chromatin and activation. MCM5 is highly expressed in proliferating tissues and is a marker of cell cycle entry.
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