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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SKA3
spindle and kinetochore associated complex subunit 3
Chromosome 13 · 13q12.11
NCBI Gene: 221150Ensembl: ENSG00000165480.17HGNC: HGNC:20262UniProt: Q8IX90
87PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingmicrotubule bindingmitotic sister chromatid segregationnegative regulation of mitotic spindle assembly checkpoint signalingneurodegenerative diseasespinal cord injurylysosomal storage diseasehepatocellular carcinoma
✦AI Summary

SKA3 (spindle and kinetochore associated complex subunit 3) is a component of the outer kinetochore that plays essential roles in chromosome 13 during cell division and has emerged as a significant oncogene in multiple cancers. As part of the SKA1 complex, SKA3 directly binds microtubules and facilitates proper chromosome 13 by enabling processive movement along depolymerizing microtubules 123. Beyond its mitotic functions, SKA3 exhibits oncogenic properties through diverse mechanisms. In cholangiocarcinoma, hypoxia-induced SKA3 promotes tumor progression by recruiting PARP1 to enhance HIF-1α PARylation, leading to HIF-1α stabilization and increased fatty acid synthesis 4. In lung adenocarcinoma, SKA3 facilitates metastasis through multiple pathways: it promotes hypoxia tolerance by disrupting PHD2-HIF-1α interactions, enabling metabolic reprogramming for liver colonization 5, and creates an EGFR/E2F1/SKA3/integrin β1 signaling loop that enhances cell migration and invasion 6. SKA3 is consistently overexpressed across various cancers including non-small cell lung cancer 7 and gastric cancer 8, correlating with poor patient prognosis 9. These findings establish SKA3 as both a potential diagnostic biomarker and therapeutic target, representing a promising avenue for precision cancer treatment 10.

Sources cited
1
SKA3 is part of the SKA1 complex that directly associates with microtubules and facilitates processive movement along depolymerizing microtubules
PMID: 19289083
2
SKA1 complex containing SKA3 is essential for proper chromosome segregation
PMID: 19360002
3
SKA3 complex enhances microtubule affinity synergistically with ndc-80 complex
PMID: 23085020
4
Hypoxia-induced SKA3 promotes cholangiocarcinoma progression by recruiting PARP1 to enhance HIF-1α PARylation and fatty acid synthesis
PMID: 37821935
5
SKA3 promotes hypoxia tolerance in lung adenocarcinoma by disrupting PHD2-HIF-1α interactions and enabling metabolic reprogramming for liver metastasis
PMID: 41298345
6
SKA3 creates an EGFR/E2F1/SKA3/integrin β1 signaling loop that promotes lung adenocarcinoma progression
PMID: 40056339
7
SKA3 is highly expressed in non-small cell lung cancer and promotes cell proliferation and metastasis
PMID: 34533066
8
SKA3 is overexpressed in gastric cancer and enhances tumor development
PMID: 36134741
9
SKA3 exhibits aberrant expression patterns across multiple cancers and correlates with poor patient prognosis
PMID: 40007126
10
SKA3 represents a potential therapeutic target for precision cancer treatment
PMID: 38241327
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.39Weak
spinal cord injuryOpen Targets
0.16Weak
lysosomal storage diseaseOpen Targets
0.14Weak
hepatocellular carcinomaOpen Targets
0.11Weak
lung adenocarcinomaOpen Targets
0.11Weak
neoplasmOpen Targets
0.09Suggestive
urinary bladder carcinomaOpen Targets
0.09Suggestive
laryngeal squamous cell carcinomaOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.08Suggestive
gastric cancerOpen Targets
0.08Suggestive
cholangiocarcinomaOpen Targets
0.08Suggestive
renal cell carcinomaOpen Targets
0.07Suggestive
cancerOpen Targets
0.06Suggestive
Mobius syndromeOpen Targets
0.05Suggestive
colorectal carcinomaOpen Targets
0.03Suggestive
non-small cell lung carcinomaOpen Targets
0.03Suggestive
uterine leiomyosarcomaOpen Targets
0.03Suggestive
osteosarcomaOpen Targets
0.03Suggestive
glioblastoma multiformeOpen Targets
0.03Suggestive
gliomaOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
KIF4AProtein interaction95%SPDL1Protein interaction91%KNL1Protein interaction91%BOD1Protein interaction91%SPC24Protein interaction91%AURKBProtein interaction91%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
27%
Lung
2%
Heart
1%
Liver
1%
Ovary
1%
Gene Interaction Network
Click a node to explore
SKA3KIF4ASPDL1KNL1BOD1SPC24AURKB
PROTEIN STRUCTURE
Preparing viewer…
PDB4AJ5 · 3.32 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.21LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.86 [0.62–1.21]
RankingsWhere SKA3 stands among ~20K protein-coding genes
  • #5,514of 20,598
    Most Researched87
  • #12,681of 17,882
    Most Constrained (LOEUF)1.21
Genes detectedSKA3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Hypoxia-induced SKA3 promoted cholangiocarcinoma progression and chemoresistance by enhancing fatty acid synthesis via the regulation of PAR-dependent HIF-1a deubiquitylation.
PMID: 37821935
J Exp Clin Cancer Res · 2023
1.00
2
Pembrolizumab and chemotherapy in high-risk, early-stage, ER
PMID: 39838117
Nat Med · 2025
0.90
3
SKA3 targeted therapies in cancer precision surgery: bridging bench discoveries to clinical applications - review article.
PMID: 38241327
Int J Surg · 2024
0.80
4
PMID: 34533066
Per Med · 2022
0.70
5
Pan-Cancer Analysis Reveals SKA3 as a Potential Diagnostic and Prognostic Biomarker.
PMID: 40007126
APMIS · 2025
0.60