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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TSSK6
testis specific serine kinase 6
Chromosome 19 · 19p13.11
NCBI Gene: 83983Ensembl: ENSG00000178093.14HGNC: HGNC:30410UniProt: A0A024R7Q5
19PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
magnesium ion bindingprotein serine/threonine kinase activityprotein bindingATP bindingazoospermiaschizophreniapartial chromosome Y deletionspermatogenic failure, X-linked, 3
✦AI Summary

TSSK6 is a testis-specific serine/threonine kinase with critical roles in male reproduction and emerging oncogenic functions. In normal physiology, TSSK6 is essential for spermatogenesis, localizing to spermatid and regulating sperm development through MYC-related pathway suppression 1. TSSK6 knockout mice exhibit infertility with reduced sperm count, motility, and increased morphological abnormalities 2, while zebrafish studies confirm its evolutionary conservation and role in testis development and sperm quality 3. At the molecular level, TSSK6 likely functions as a serine/threonine kinase mediating phosphorylation events critical for spermatogenesis and male fertility. Clinically, TSSK6 demonstrates an oncogenic dual nature when aberrantly expressed. As a cancer testis antigen, TSSK6 is frequently upregulated in colorectal cancer, where elevated expression correlates with reduced relapse-free survival 45. Mechanistically, TSSK6 kinase activity promotes anchorage-independent growth, invasion, and focal adhesion formation in cancer cells 4. In somatic contexts, TSSK6 can confer malignant properties to semi-transformed epithelial cells independently 5. Pharmacoeconomically, TSSK6 emerged as a druggable target across multiple disease contexts: colorectal cancer precision therapy 6, myopia pathogenesis 7, and seborrheic keratosis susceptibility 8. Its restricted normal expression suggests a potentially broad therapeutic window with minimal off-target effects in non-reproductive tissues.

Sources cited
1
TSSK6 is frequently anomalously expressed in colorectal cancer; elevated expression correlates with reduced relapse-free survival; TSSK6 kinase activity is essential for oncogenic behaviors including anchorage independence and invasion
PMID: 38762178
2
TSSK6 exhibits oncogenic activity when abnormally expressed in colorectal cancer cells; ectopic TSSK6 expression in semi-transformed colonic epithelial cells confers anchorage independence and enhances invasion; TSSK6 enhances focal adhesion formation
PMID: 38260312
3
TSSK6 is lowly expressed in non-obstructive azoospermia; located in spermatid; may be involved in repression of MYC-related pathways during spermatogenesis
PMID: 37227814
4
TSSK6 gene polymorphism c.822+126T>G/C is associated with spermatogenic impairment; male Tssk6 knockout mice are infertile with reduced sperm count, decreased motility, and abnormal morphology
PMID: 20037600
5
Tssk6 is highly expressed in testis of adult male zebrafish; deletion leads to impaired testis development, reduced sperm quality, and decreased fertilization capacity; gene is evolutionarily conserved across vertebrates
PMID: 40570569
6
TSSK6 identified as one of six promising druggable targets for colorectal cancer with minimal off-target effects through Mendelian randomization and colocalization analysis
PMID: 40496862
7
TSSK6 identified as putative genetically causal target for myopia backed by colocalization evidence in adult blood eQTL datasets
PMID: 39110588
8
TSSK6 is a significant druggable gene associated with seborrheic keratosis susceptibility; may influence skin tumor onset through cell differentiation and programmed apoptosis regulation
PMID: 39918628
Disease Associationsⓘ20
azoospermiaOpen Targets
0.11Weak
schizophreniaOpen Targets
0.11Weak
partial chromosome Y deletionOpen Targets
0.09Suggestive
spermatogenic failure, X-linked, 3Open Targets
0.09Suggestive
spermatogenic failure 40Open Targets
0.09Suggestive
spermatogenic failure 76Open Targets
0.09Suggestive
spermatogenic failure 80Open Targets
0.09Suggestive
spermatogenic failure 47Open Targets
0.09Suggestive
spermatogenic failure 65Open Targets
0.09Suggestive
spermatogenic failure 84Open Targets
0.09Suggestive
spermatogenic failure 93Open Targets
0.09Suggestive
spermatogenic failure 54Open Targets
0.09Suggestive
spermatogenic failure 10Open Targets
0.09Suggestive
spermatogenic failure 11Open Targets
0.09Suggestive
spermatogenic failure 56Open Targets
0.09Suggestive
spermatogenic failure 92Open Targets
0.09Suggestive
spermatogenic failure 94Open Targets
0.09Suggestive
spermatogenic failure 79Open Targets
0.09Suggestive
spermatogenic failure 58Open Targets
0.08Suggestive
spermatogenic failure 8Open Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
HSP90AB1Protein interaction100%TSKSProtein interaction73%TNP1Protein interaction62%ARMC3Shared pathway50%TSSK4Shared pathway40%TTC21AShared pathway33%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
97%
Ovary
46%
Brain
40%
Lung
29%
Heart
25%
Gene Interaction Network
Click a node to explore
TSSK6HSP90AB1TSKSTNP1ARMC3TSSK4TTC21A
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9BXA6
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.91LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.38 [0.80–1.91]
RankingsWhere TSSK6 stands among ~20K protein-coding genes
  • #14,584of 20,598
    Most Researched19
  • #17,318of 17,882
    Most Constrained (LOEUF)1.91
Genes detectedTSSK6
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Integrative genomic and single-cell framework identifies druggable targets for colorectal cancer precision therapy.
PMID: 40496862
Front Immunol · 2025
1.00
2
Identification of Potential Drug Targets for Myopia Through Mendelian Randomization.
PMID: 39110588
Invest Ophthalmol Vis Sci · 2024
0.90
3
Testis-specific serine kinase 6 (TSSK6) is abnormally expressed in colorectal cancer and promotes oncogenic behaviors.
PMID: 38762178
J Biol Chem · 2024
0.80
4
Identification and validation of diagnostic signature genes in non-obstructive azoospermia by machine learning.
PMID: 37227814
Aging (Albany NY) · 2023
0.70
5
The Cancer Testis Antigen Testis Specific Serine Kinase 6 (TSSK6) is abnormally expressed in colorectal cancer and promotes oncogenic behaviors.
PMID: 38260312
bioRxiv · 2024
0.60