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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SAV1
salvador family WW domain containing protein 1
Chromosome 14 · 14q22.1
NCBI Gene: 60485Ensembl: ENSG00000151748.16HGNC: HGNC:17795UniProt: B3KTQ1
93PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
hippo signalingprotein bindingidentical protein bindingprotein serine/threonine kinase activator activityhypertensioncardiovascular diseasevein disorderlymphatic system disease
✦AI Summary

SAV1 (salvador family WW domain containing protein 1) functions as a critical regulatory component of the Hippo signaling pathway, serving as a tumor suppressor that controls organ size and prevents tumorigenesis. SAV1 forms complexes with MST1/MST2 kinases to activate downstream LATS1/2 kinases, which subsequently phosphorylate and inactivate YAP1/TAZ oncoproteins, preventing their nuclear translocation and proliferation-promoting transcriptional activity 12. The protein undergoes post-translational regulation through various mechanisms, including sulfation by SLC35B2 under oxidative stress conditions, which disrupts SAV1-MST1 complex formation and inactivates Hippo signaling in hepatocellular carcinoma 3. SAV1 functions within phase-separated biomolecular condensates that facilitate Hippo pathway activation 4. Clinically, SAV1 acts as a tumor suppressor across multiple cancer types. SAV1 mutations occur in intrahepatic cholangiocarcinoma and are associated with poor patient outcomes 5. In non-small cell lung cancer, smoking-induced SAV1 promoter hypermethylation disrupts YAP negative feedback regulation, promoting malignant progression 6. Additionally, SAV1 expression is decreased in gastric cancer tissues and correlates with better patient survival, with KDM2B transcriptionally regulating SAV1 levels 7. These findings establish SAV1 as a key tumor suppressor with significant therapeutic potential.

Sources cited
1
SAV1 regulation of Hippo signaling pathway and its role in cholangiocyte proliferation
PMID: 36799463
2
PKN2-SAV1-TAZ signaling mechanism in mesenchymal-like cancer cell growth
PMID: 39560431
3
SLC35B2-mediated sulfation of SAV1 disrupts MST1 complex formation and inactivates Hippo signaling
PMID: 38377452
4
SAV1 participation in phase-separated biomolecular condensates for Hippo pathway activation
PMID: 36807601
5
SAV1 mutations in intrahepatic cholangiocarcinoma and association with patient outcomes
PMID: 39551842
6
Smoking-induced SAV1 promoter hypermethylation disrupts YAP negative feedback in lung cancer
PMID: 35864957
7
SAV1 expression decrease in gastric cancer and KDM2B transcriptional regulation
PMID: 37033161
Disease Associationsⓘ20
hypertensionOpen Targets
0.47Moderate
cardiovascular diseaseOpen Targets
0.32Weak
lymphatic system diseaseOpen Targets
0.25Weak
vein disorderOpen Targets
0.25Weak
hereditary spastic paraplegia 3AOpen Targets
0.19Weak
spinal cord injuryOpen Targets
0.19Weak
genetic disorderOpen Targets
0.17Weak
Dupuytren ContractureOpen Targets
0.14Weak
Hereditary breast and ovarian cancer syndromeOpen Targets
0.14Weak
Palmar FibromatosisOpen Targets
0.14Weak
hereditary breast ovarian cancer syndromeOpen Targets
0.13Weak
lumbar disc herniationOpen Targets
0.13Weak
hereditary sensory and autonomic neuropathy type 1Open Targets
0.12Weak
neoplasmOpen Targets
0.10Weak
lung cancerOpen Targets
0.10Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
Varicose veinsOpen Targets
0.09Suggestive
renal cell carcinomaOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
gastric cancerOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DIAPH1Protein interaction99%GFERProtein interaction99%MOB1AProtein interaction99%RASSF1Protein interaction97%LIMD1Protein interaction96%LATS1Protein interaction96%
Tissue Expression6 tissues
Heart
100%
Ovary
73%
Brain
60%
Lung
52%
Bone Marrow
38%
Liver
34%
Gene Interaction Network
Click a node to explore
SAV1DIAPH1GFERMOB1ARASSF1LIMD1LATS1
PROTEIN STRUCTURE
Preparing viewer…
PDB6AO5 · 2.96 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.71LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.50 [0.36–0.71]
RankingsWhere SAV1 stands among ~20K protein-coding genes
  • #5,164of 20,598
    Most Researched93
  • #5,407of 17,882
    Most Constrained (LOEUF)0.71
Genes detectedSAV1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
P4HA2 induces hepatic ductular reaction and biliary fibrosis in chronic cholestatic liver diseases.
PMID: 36799463
Hepatology · 2023
1.00
2
PKN2 Is a Dependency of the Mesenchymal-like Cancer Cell State.
PMID: 39560431
Cancer Discov · 2025
0.90
3
Enhanced SLC35B2/SAV1 sulfation axis promotes tumor growth by inhibiting Hippo signaling in HCC.
PMID: 38377452
Hepatology · 2025
0.80
4
Integrative molecular analysis of intrahepatic cholangiocarcinoma reveals 2 classes that have different outcomes.
PMID: 23295441
Gastroenterology · 2013
0.70
5
Phase separation of Hippo signalling complexes.
PMID: 36807601
EMBO J · 2023
0.60