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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SVIL
supervillin
Chromosome 10 · 10p11.23
NCBI Gene: 6840Ensembl: ENSG00000197321.16HGNC: HGNC:11480UniProt: A0A6I8PIX7
142PubMed Papers
21Diseases
0Drugs
5Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
focal adhesioncostamereskeletal muscle tissue developmentactin cytoskeletonmyofibrillar myopathy 10neurodegenerative diseasesialolithiasisSplenomegaly
✦AI Summary

SVIL encodes supervillin, a 205-kDa F-actin binding protein that serves as a critical link between the actin cytoskeleton and plasma membranes 1. The protein exhibits a bipartite structure with three nuclear localization signals in the N-terminus and three actin-binding sequences in the C-terminus that share homology with villin 1. SVIL functions in cytoskeletal regulation and cell division, with roles in focal adhesion modulation and cytokinesis. In disease contexts, SVIL demonstrates complex relationships with cancer progression. In bladder cancer, SVIL expression is paradoxically lower in tumor tissue compared to normal tissue, yet high SVIL expression within tumors correlates with poor prognosis 2. SVIL participates in inflammatory responses by mediating LPS-induced cytokine production (IL-6, IL-1β, TNF-α) through TLR4/NF-κB and ERK1/2 pathways in macrophages 3. In hematopoiesis, SVIL expression is regulated by serine metabolism and H3K9 methylation, with downregulation impairing megakaryocyte differentiation and contributing to thrombocytopenia in multiple myeloma 4. Recent genetic studies identify SVIL as a novel hypertrophic cardiomyopathy disease gene, with rare truncating variants conferring approximately tenfold increased HCM risk 5. SVIL also interacts with mutant p53 to recruit chr10 modifiers, promoting gliomagenesis through epitranscriptomic dysregulation 6.

Sources cited
1
SVIL encodes a 205-kDa F-actin binding protein with bipartite structure and nuclear localization signals
PMID: 9867483
2
SVIL expression is lower in bladder cancer tissue but high expression correlates with poor prognosis
PMID: 37670039
3
SVIL mediates LPS-induced inflammatory cytokine production through TLR4/NF-κB and ERK1/2 pathways
PMID: 34480249
4
SVIL downregulation by serine metabolism impairs megakaryocyte differentiation and causes thrombocytopenia
PMID: 37055385
5
Rare truncating SVIL variants confer tenfold increased risk of hypertrophic cardiomyopathy
PMID: 39966646
6
SVIL interacts with mutant p53 to recruit chromatin modifiers and promote gliomagenesis
PMID: 36973285
Disease Associationsⓘ21
myofibrillar myopathy 10Open Targets
0.59Moderate
neurodegenerative diseaseOpen Targets
0.40Moderate
sialolithiasisOpen Targets
0.34Weak
SplenomegalyOpen Targets
0.32Weak
biliary tract diseaseOpen Targets
0.32Weak
AnisometropiaOpen Targets
0.31Weak
DNA methylationOpen Targets
0.28Weak
ApneaOpen Targets
0.27Weak
osteoarthritis, hipOpen Targets
0.27Weak
Abnormal brain morphologyOpen Targets
0.27Weak
response to stimulusOpen Targets
0.26Weak
ovarian neoplasmOpen Targets
0.25Weak
secondary malignant neoplasmOpen Targets
0.25Weak
Alzheimer diseaseOpen Targets
0.23Weak
lysosomal storage diseaseOpen Targets
0.23Weak
multiple sclerosisOpen Targets
0.23Weak
Parkinson diseaseOpen Targets
0.23Weak
ShockOpen Targets
0.19Weak
Subdural hemorrhageOpen Targets
0.18Weak
nephritisOpen Targets
0.16Weak
Myopathy, myofibrillar, 10UniProt
Pathogenic Variants5
NM_021738.3(SVIL):c.8+1G>ALikely pathogenic
not provided
★☆☆☆2022
NM_021738.3(SVIL):c.5101-1G>ALikely pathogenic
not provided
★☆☆☆2022
NM_021738.3(SVIL):c.3626C>T (p.Ser1209Leu)Likely pathogenic
Abnormal brain morphology
★☆☆☆→ Residue 1209
NM_021738.3(SVIL):c.4812C>A (p.Tyr1604Ter)Pathogenic
Myofibrillar myopathy 10
☆☆☆☆2021→ Residue 1604
NM_021738.3(SVIL):c.3578_3579del (p.Val1193fs)Pathogenic
Myofibrillar myopathy 10
☆☆☆☆2020→ Residue 1193
View on ClinVar ↗
Related Genes
KIF14Protein interaction77%ACTBProtein interaction72%CTTNProtein interaction71%VILLShared pathway57%FLIIShared pathway33%CAPGShared pathway33%
Tissue Expression6 tissues
Heart
100%
Ovary
36%
Lung
19%
Brain
7%
Bone Marrow
5%
Liver
4%
Gene Interaction Network
Click a node to explore
SVILKIF14ACTBCTTNVILLFLIICAPG
PROTEIN STRUCTURE
Preparing viewer…
PDB2K6M · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.48Moderately Constrained
pLIⓘ
0.12Tolerant
Observed/Expected LoF0.41 [0.35–0.48]
RankingsWhere SVIL stands among ~20K protein-coding genes
  • #3,238of 20,598
    Most Researched142 · top quartile
  • #3,503of 5,498
    Most Pathogenic Variants5
  • #2,851of 17,882
    Most Constrained (LOEUF)0.48 · top quartile
Genes detectedSVIL
Sources retrieved10 papers
Response time—
📄 Sources
10â–¼
1
Deep learning enables genetic analysis of the human thoracic aorta.
PMID: 34837083
Nat Genet · 2022
1.00
2
AKT1
PMID: 40135844
Adv Sci (Weinh) · 2025
0.90
3
Cloning, characterization, and chromosomal localization of human superillin (SVIL).
PMID: 9867483
Genomics · 1998
0.80
4
Duality of the SVIL expression in bladder cancer and its correlation with immune infiltration.
PMID: 37670039
Sci Rep · 2023
0.70
5
Supervillin Contributes to LPS-induced Inflammatory Response in THP-1 Cell-derived Macrophages.
PMID: 34480249
Inflammation · 2022
0.60