SMC4: Structural Maintenance of Chromosomes 4
A key component of the condensin complex involved in chromosome condensation and segregation.
Gene Information Card
| Symbol | SMC4 |
|---|---|
| Full Name | Structural Maintenance of Chromosomes 4 |
| Gene Type | Protein-coding |
| Chromosomal Location | 3q26.1 |
| NCBI Gene ID | 10051 ncbi.nlm.nih.gov/gene/10051 |
| Ensembl ID | ENSG00000113810 |
| UniProt ID | Q9NTJ3 |
| OMIM ID | 606744 |
| HGNC ID | 11113 |
| Aliases | SMC4L1, CAP-C, CAPC, hCAP-C |
Description
SMC4 encodes a core subunit of the condensin complex, which is essential for chromosome condensation and segregation during mitosis and meiosis. The protein belongs to the structural maintenance of chromosomes (SMC) family and functions as an ATPase that organizes higher-order chromatin structure. SMC4 is widely expressed and its dysregulation is implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | Overexpression of SMC4 promotes chromosome instability and tumor progression. | PMID: 25686104 |
| Hepatocellular Carcinoma | Upregulation of SMC4 correlates with poor prognosis and increased cell proliferation. | PMID: 29393419 |
| Colorectal Cancer | SMC4 amplification drives aneuploidy and resistance to chemotherapy. | PMID: 27562872 |
| Cornelia de Lange Syndrome (CdLS) | Mutations in SMC4 are associated with CdLS-like phenotypes, affecting cohesin pathway. | PMID: 28135719 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Bone Marrow | 15.2 | Medium |
| Lymph Node | 12.8 | Medium |
| Brain | 4.1 | Low |
| Liver | 6.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 32.1 | Cervical cancer cell line; high expression |
| K562 | 18.4 | Leukemia cell line; moderate expression |
| HepG2 | 22.7 | Hepatocellular carcinoma; elevated |
| MCF7 | 14.5 | Breast cancer; moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2143G>A (p.Gly715Arg) | Missense | 0.02% | Unknown functional impact; reported in COSMIC |
| c.2870C>T (p.Thr957Met) | Missense | 0.01% | Potential loss of ATPase activity |
| c.1234_1235insA | Frameshift | <0.01% | Truncation; likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations in SMC4 are predicted to cause loss of condensin function, impairing chromosome condensation.
Gain of Function (GOF)
Missense mutations in the ATPase domain may lead to hyperactive condensation, observed in some cancers.
Dominant Negative (DN)
Certain missense mutations (e.g., in the hinge domain) can disrupt complex assembly, acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • kinetochore (GO:0000776) | • condensin complex (GO:0000796) |
| • ATP binding (GO:0005524) | • nucleus (GO:0005634) |
| • chromosome segregation (GO:0007059) | • chromosome condensation (GO:0030261) |
Pathways
• Condensin complex (Reactome: R-HSA-141444)
• Mitotic Prophase (Reactome: R-HSA-68875)
• Chromosome Maintenance (KEGG: hsa03030)
Protein Summary
SMC4 is a 1285-amino acid protein that forms a heterodimer with SMC2, the core of the condensin complex. It contains an N-terminal nucleotide-binding domain, a central hinge region, and a C-terminal domain. The protein undergoes ATP-dependent conformational changes to facilitate chromosome looping and compaction. Post-translational modifications include phosphorylation by CDK1 during mitosis, regulating its activity.
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