SPC25: A Key Component of the NDC80 Kinetochore Complex
Essential for Chromosome Segregation and Mitotic Fidelity
Gene Information Card
| Symbol | SPC25 |
|---|---|
| Full Name | SPC25 component of NDC80 kinetochore complex |
| Gene Type | Protein coding |
| Chromosomal Location | 2q24.3 |
| NCBI Gene ID | 57405 ncbi.nlm.nih.gov/gene/57405 |
| Ensembl ID | ENSG00000115956 |
| UniProt ID | Q9HBM1 |
| OMIM ID | 609391 |
| HGNC ID | 24024 |
| Aliases | SPC25, hSPC25, NDC80 complex component SPC25 |
Description
SPC25 encodes a component of the NDC80 kinetochore complex, which is essential for proper chromosome segregation during mitosis. The complex forms a stable bridge between kinetochores and spindle microtubules, ensuring accurate chromosome alignment and segregation. SPC25 interacts with other NDC80 complex subunits (SPC24, NDC80, NUF2) and is critical for mitotic checkpoint signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression of SPC25 promotes tumor growth and metastasis | PMID: 31239444 |
| Lung cancer | Upregulation associated with poor prognosis and cell proliferation | PMID: 31591465 |
| Colorectal cancer | High expression linked to tumor progression and chemoresistance | PMID: 32015547 |
| Hepatocellular carcinoma | SPC25 knockdown inhibits cell cycle and induces apoptosis | PMID: 30728374 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | High |
| Bone marrow | 8.3 | Medium |
| Lymph node | 6.1 | Medium |
| Brain | 1.2 | Low |
| Heart | 0.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line |
| A549 | 11.4 | Lung cancer cell line |
| MCF7 | 9.8 | Breast cancer cell line |
| HepG2 | 7.6 | Liver cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G | Missense | 0.01% | p.Met1Val; potential loss of start codon |
| c.214C>T | Nonsense | 0.005% | p.Arg72*; premature truncation |
| c.487G>A | Missense | 0.02% | p.Gly163Arg; altered protein stability |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated or unstable protein, impairing kinetochore assembly and mitotic progression.
Gain of Function (GOF)
Not well characterized; overexpression in cancers may confer proliferative advantage.
Dominant Negative (DN)
Missense mutations that disrupt NDC80 complex integrity without complete loss of function.
View complete mutation data：
Gene Ontology (GO)
| • kinetochore (GO:0000776) | • condensed chromosome kinetochore (GO:0000777) |
| • spindle (GO:0005819) | • chromosome segregation (GO:0007059) |
| • mitotic nuclear division (GO:0007067) | • microtubule binding (GO:0008017) |
| • cell division (GO:0051301) |
Pathways
• Cell cycle (KEGG: hsa04110)
• Oocyte meiosis (KEGG: hsa04114)
• Progesterone-mediated oocyte maturation (KEGG: hsa04914)
Protein Summary
SPC25 is a 224-amino acid protein that forms a heterodimer with SPC24, which then associates with NDC80 and NUF2 to form the NDC80 complex. This complex is a key component of the outer kinetochore, directly binding microtubules and regulating chromosome movement. SPC25 contains a coiled-coil domain essential for complex assembly and is phosphorylated during mitosis to regulate its activity.
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