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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SPC25
SPC25 component of NDC80 kinetochore complex
Chromosome 2 · 2q24.3
NCBI Gene: 57405Ensembl: ENSG00000152253.10HGNC: HGNC:24031UniProt: Q9HBM1
56PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingmitotic spindle organizationchromosome segregationcytosolneurodegenerative diseaseAbnormality of the skeletal systemHypercholesterolemiadiabetic retinopathy
✦AI Summary

SPC25 is a critical component of the NDC80 kinetochore complex essential for proper chromosome 2 and spindle checkpoint function 12. It organizes stable microtubule binding sites at the kinetochore's outer plate and synergistically enhances the SKA1 complex's microtubule affinity, enabling tracking of depolymerizing microtubules 3. Beyond its canonical mitotic role, SPC25 has emerged as a significant oncogenic driver across multiple cancer types. In epithelial ovarian cancer, SPC25 functions as a scaffolding protein orchestrating an SPC25/RIOK1/MYH9 complex that promotes cancer stem cell phenotypes and platinum resistance through Wnt/β-catenin pathway activation 4. In lung adenocarcinoma, SPC25 upregulation associates with poor prognosis and promotes glycolysis, cell cycle progression, and ferroptosis dysregulation 56. Similar oncogenic roles occur in breast cancer and hepatocellular carcinoma, where elevated SPC25 correlates with reduced survival and accelerated cell cycle progression 78. In lung cancer with idiopathic pulmonary fibrosis, SPC25 mutations increase expression and promote epithelial-to-mesenchymal transition 9. Recent evidence shows berberine suppresses non-small cell lung cancer through SPC25/NUF2 axis inhibition 10. These findings establish SPC25 as a promising therapeutic target and prognostic biomarker across multiple malignancies.

Sources cited
1
SPC25 is an essential NDC80 complex component required for chromosome segregation, spindle checkpoint activity, and kinetochore integrity
PMID: 14699129
2
SPC25 organizes stable microtubule binding sites at the kinetochore outer plate
PMID: 14738735
3
NDC80 complex synergistically enhances SKA1 complex affinity for microtubules and enables tracking of depolymerizing microtubules
PMID: 23085020
4
SPC25 promotes epithelial ovarian cancer stemness and platinum resistance by scaffolding the SPC25/RIOK1/MYH9 complex, activating Wnt/β-catenin signaling
PMID: 39488790
5
SPC25 upregulation in lung adenocarcinoma associates with poor prognosis and promotes glycolysis, ferroptosis dysregulation, and cell cycle progression
PMID: 38217547
6
SPC25 serves as a prognostic and immune-related biomarker in lung adenocarcinoma through centrosome assembly checkpoint regulation
PMID: 40691691
7
SPC25 upregulation in breast cancer promotes cell proliferation and associates with shorter survival and increased recurrence probability
PMID: 31400751
8
SPC25 overexpression promotes hepatocellular carcinoma proliferation by accelerating cell cycle and is a poor prognostic marker
PMID: 33408271
9
SPC25 mutations are frequent in lung cancer with idiopathic pulmonary fibrosis and promote epithelial-to-mesenchymal transition through TGF-β1 signaling
PMID: 34746885
10
Berberine inhibits non-small cell lung cancer through suppression of the SPC25/NUF2 pathway, reducing cell growth, invasion, and glycolysis
PMID: 39755832
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.47Moderate
Abnormality of the skeletal systemOpen Targets
0.40Moderate
HypercholesterolemiaOpen Targets
0.32Weak
diabetic retinopathyOpen Targets
0.20Weak
diabetic eye diseaseOpen Targets
0.20Weak
gestational diabetesOpen Targets
0.17Weak
type 2 diabetes mellitusOpen Targets
0.13Weak
hepatocellular carcinomaOpen Targets
0.12Weak
lung adenocarcinomaOpen Targets
0.10Weak
cancerOpen Targets
0.10Suggestive
neoplasmOpen Targets
0.10Suggestive
metabolic syndromeOpen Targets
0.10Suggestive
breast cancerOpen Targets
0.08Suggestive
posterior cortical atrophyOpen Targets
0.08Suggestive
esophageal squamous cell carcinomaOpen Targets
0.08Suggestive
Alzheimer diseaseOpen Targets
0.08Suggestive
glucose metabolism diseaseOpen Targets
0.07Suggestive
idiopathic pulmonary fibrosisOpen Targets
0.07Suggestive
Abnormal glucose homeostasisOpen Targets
0.07Suggestive
renal cell carcinomaOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NSL1Protein interaction100%MIS12Protein interaction99%CENPAProtein interaction98%CDC20Protein interaction98%CENPFProtein interaction98%UBE2CProtein interaction97%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
94%
Lung
7%
Ovary
5%
Liver
4%
Heart
3%
Gene Interaction Network
Click a node to explore
SPC25NSL1MIS12CENPACDC20CENPFUBE2C
PROTEIN STRUCTURE
Preparing viewer…
PDB2VE7 · 2.88 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.15LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.76 [0.51–1.15]
RankingsWhere SPC25 stands among ~20K protein-coding genes
  • #8,140of 20,598
    Most Researched56
  • #12,021of 17,882
    Most Constrained (LOEUF)1.15
Genes detectedSPC25
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian Cancer.
PMID: 39488790
Adv Sci (Weinh) · 2024
1.00
2
CADM1 and SPC25 Gene Mutations in Lung Cancer Patients With Idiopathic Pulmonary Fibrosis.
PMID: 34746885
JTO Clin Res Rep · 2021
0.90
3
Structure of the human signal peptidase complex reveals the determinants for signal peptide cleavage.
PMID: 34388369
Mol Cell · 2021
0.80
4
Up-regulation of SPC25 promotes breast cancer.
PMID: 31400751
Aging (Albany NY) · 2019
0.70
5
SPC25 as a novel therapeutic and prognostic biomarker and its association with glycolysis, ferroptosis and ceRNA in lung adenocarcinoma.
PMID: 38217547
Aging (Albany NY) · 2024
0.60