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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SSH3
slingshot protein phosphatase 3
Chromosome 11 · 11q13.2
NCBI Gene: 54961Ensembl: ENSG00000172830.14HGNC: HGNC:30581UniProt: Q8TE77
33PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingphosphoprotein phosphatase activityactin bindingactin cytoskeleton organizationAbruptio Placentaeosteoarthritisresponse to xenobiotic stimulusrheumatic disease
✦AI Summary

SSH3 (slingshot protein phosphatase 3) is a serine/threonine phosphatase that regulates actin cytoskeleton dynamics by dephosphorylating and activating cofilin, an actin-depolymerizing factor that promotes actin filament disassembly 1. SSH3 is expressed in multiple cell types and functions downstream of integrin-Rac1 signaling, where its activity is regulated by 14-3-3 protein binding to control cell migration and polarity 1. Beyond its canonical role in actin regulation, SSH3 has emerged as a significant oncogene in multiple cancer types. In hepatocellular carcinoma, SSH3 is upregulated in tumor tissues and promotes malignant progression by activating the FGF1-mediated FGF/FGFR signaling pathway, enhancing cell proliferation while suppressing apoptosis 2. Similarly, in pancreatic cancer, elevated SSH3 expression correlates with advanced pathological grade and staging, promoting cancer cell proliferation and migration through Notch signaling pathway activation 3. SSH3 has been identified as a potential tumor antigen in bladder urothelial carcinoma for mRNA vaccine development 4. Clinically, SSH3 represents a novel therapeutic target for cancer treatment. Additionally, SSH3 DNA methylation shows longitudinal associations with lung function and may serve as a biomarker for lung function deficit prediction 5, while SSH3 has been identified as a potential biomarker for Alzheimer's disease diagnosis 6.

Sources cited
1
SSH3 dephosphorylates and activates cofilin to regulate actin cytoskeleton; SSH3 activity is regulated by 14-3-3 protein binding downstream of Rac1 signaling in keratinocytes
PMID: 17848544
2
SSH3 is upregulated in hepatocellular carcinoma tissues and promotes malignant progression through FGF1-mediated FGF/FGFR pathway activation
PMID: 33275222
3
SSH3 expression is elevated in pancreatic cancer and correlates with advanced grade and staging; SSH3 promotes pancreatic cancer proliferation and migration via Notch signaling activation
PMID: 38726290
4
SSH3 is identified as a potential tumor antigen for developing mRNA-based vaccines against bladder urothelial carcinoma
PMID: 36761744
5
DNA methylation at SSH3 locus shows longitudinal association with lung function and may serve as a biomarker for lung function deficit prediction
PMID: 34235211
6
SSH3 is identified as a potential biomarker for Alzheimer's disease diagnosis
PMID: 32019384
Disease Associationsⓘ20
Abruptio PlacentaeOpen Targets
0.28Weak
osteoarthritisOpen Targets
0.17Weak
response to xenobiotic stimulusOpen Targets
0.12Weak
rheumatic diseaseOpen Targets
0.12Weak
prostate carcinomaOpen Targets
0.07Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
osteoarthritis, hipOpen Targets
0.03Suggestive
total hip arthroplastyOpen Targets
0.03Suggestive
colorectal carcinomaOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
myxosarcomaOpen Targets
0.01Suggestive
colorectal cancerOpen Targets
0.01Suggestive
posterior cortical atrophyOpen Targets
0.01Suggestive
chronic interstitial cystitisOpen Targets
0.01Suggestive
bladder transitional cell carcinomaOpen Targets
0.00Suggestive
corneal diseaseOpen Targets
0.00Suggestive
transitional cell carcinoma of kidneyOpen Targets
0.00Suggestive
cancerOpen Targets
0.00Suggestive
tauopathyOpen Targets
0.00Suggestive
invasive breast ductal carcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CFL1Protein interaction99%CFL2Protein interaction99%LIMK1Protein interaction99%PPP3CAProtein interaction91%PPP3CBProtein interaction91%PPP3CCProtein interaction91%
Tissue Expression6 tissues
Ovary
100%
Lung
60%
Liver
49%
Bone Marrow
43%
Heart
35%
Brain
14%
Gene Interaction Network
Click a node to explore
SSH3CFL1CFL2LIMK1PPP3CAPPP3CBPPP3CC
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8TE77
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.07LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.87 [0.71–1.07]
RankingsWhere SSH3 stands among ~20K protein-coding genes
  • #11,428of 20,598
    Most Researched33
  • #10,790of 17,882
    Most Constrained (LOEUF)1.07
Genes detectedSSH3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Identification of tumor antigens and immune landscapes for bladder urothelial carcinoma mRNA vaccine.
PMID: 36761744
Front Immunol · 2023
1.00
2
SSH3 promotes pancreatic cancer proliferation and migration by activating the notch signaling pathway.
PMID: 38726290
Am J Cancer Res · 2024
0.90
3
SSH3 promotes malignant progression of HCC by activating FGF1-mediated FGF/FGFR pathway.
PMID: 33275222
Eur Rev Med Pharmacol Sci · 2020
0.80
4
Identification of dysregulated genes and pathways of different brain regions in Alzheimer's disease.
PMID: 32019384
Int J Neurosci · 2020
0.70
5
Proinflammatory cytokines suppress nonsense-mediated RNA decay to impair regulated transcript isoform processing in pancreatic β cells.
PMID: 38586449
Front Endocrinol (Lausanne) · 2024
0.60