Browse VHL

Summary
SymbolVHL
Namevon Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase
Aliases VHL1; von Hippel-Lindau syndrome; von Hippel-Lindau tumor suppressor; RCA11; pVHL; elongin binding protein; ......
Chromosomal Location3p25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Isoform 1: Cytoplasm. Membrane; Peripheral membrane protein. Nucleus. Note=Found predominantly in the cytoplasm and with less amounts nuclear or membrane-associated. Colocalizes with ADRB2 at the cell membrane.; SUBCELLULAR LOCATION: Isoform 3: Cytoplasm. Nucleus. Note=Equally distributed between the nucleus and the cytoplasm but not membrane-associated.
Domain PF01847 VHL beta domain
PF17211 VHL box domain
Function

Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as a target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an oxygen-responsive manner, ADRB2.

> Gene Ontology
 
Biological Process GO:0001666 response to hypoxia
GO:0031647 regulation of protein stability
GO:0036293 response to decreased oxygen levels
GO:0036294 cellular response to decreased oxygen levels
GO:0043618 regulation of transcription from RNA polymerase II promoter in response to stress
GO:0043620 regulation of DNA-templated transcription in response to stress
GO:0050821 protein stabilization
GO:0061418 regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0061428 negative regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0070482 response to oxygen levels
GO:0071453 cellular response to oxygen levels
GO:0071456 cellular response to hypoxia
GO:0097201 negative regulation of transcription from RNA polymerase II promoter in response to stress
Molecular Function GO:0004842 ubiquitin-protein transferase activity
GO:0008134 transcription factor binding
GO:0019787 ubiquitin-like protein transferase activity
GO:0061630 ubiquitin protein ligase activity
GO:0061659 ubiquitin-like protein ligase activity
Cellular Component GO:0000151 ubiquitin ligase complex
GO:0000153 cytoplasmic ubiquitin ligase complex
GO:0030891 VCB complex
> KEGG and Reactome Pathway
 
KEGG hsa04066 HIF-1 signaling pathway
hsa04120 Ubiquitin mediated proteolysis
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-983168: Antigen processing
R-HSA-2262749: Cellular response to hypoxia
R-HSA-2262752: Cellular responses to stress
R-HSA-983169: Class I MHC mediated antigen processing & presentation
R-HSA-168256: Immune System
R-HSA-1234176: Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-1234174: Regulation of Hypoxia-inducible Factor (HIF) by oxygen
Summary
SymbolVHL
Namevon Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase
Aliases VHL1; von Hippel-Lindau syndrome; von Hippel-Lindau tumor suppressor; RCA11; pVHL; elongin binding protein; ......
Chromosomal Location3p25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between VHL and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between VHL and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28235946Clear Cell Renal Cell CarcinomaPromote immunityVascular cell adhesion molecule 1 (VCAM-1) is an adhesion molecule assigned to the activated endothelium mediating immune cells adhesion and extravasation. VHL promotes immune response against renal cell carcinoma via NF-κB-dependent regulation of VCAM-1.
26707870Clear Cell Renal Cell CarcinomaPromote immunity (T cell function)Our work provides the first evidence that VHL mutations positively correlate with PD-L1 expression in ccRCC and may influence the response to ccRCC anti-PD-L1/PD-1 immunotherapy.
21258414Kidney NeoplasmPromote immunityThe RCC6 and RCC4 cell lines were transfected with the wild-type gene to restore the function of VHL. The presence of the gene in RCC cells downregulated hypoxia-inducible factor (HIF)-1α and subsequently decreased vascular endothelial growth factor (VEGF) production. Relative to control transfectants and parental cells, pVHL-transfected cell lines activated resting and IL2-activated NK cells less strongly, as assessed by IFNγ secretion, NK degranulation and cell lysis.
Summary
SymbolVHL
Namevon Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase
Aliases VHL1; von Hippel-Lindau syndrome; von Hippel-Lindau tumor suppressor; RCA11; pVHL; elongin binding protein; ......
Chromosomal Location3p25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of VHL in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR Second most enriched score: 0.85 Sensitive to T cell-mediated killing
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolVHL
Namevon Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase
Aliases VHL1; von Hippel-Lindau syndrome; von Hippel-Lindau tumor suppressor; RCA11; pVHL; elongin binding protein; ......
Chromosomal Location3p25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of VHL in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.3570.118
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.5130.781
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.2490.865
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.3020.318
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.4590.824
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.1060.968
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.0230.952
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.2660.875
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.2010.912
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.2050.855
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.0160.503
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.1410.0403
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of VHL in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 111381.853.8280.211
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 6110010001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5126050101
Summary
SymbolVHL
Namevon Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase
Aliases VHL1; von Hippel-Lindau syndrome; von Hippel-Lindau tumor suppressor; RCA11; pVHL; elongin binding protein; ......
Chromosomal Location3p25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of VHL. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolVHL
Namevon Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase
Aliases VHL1; von Hippel-Lindau syndrome; von Hippel-Lindau tumor suppressor; RCA11; pVHL; elongin binding protein; ......
Chromosomal Location3p25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of VHL. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by VHL.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolVHL
Namevon Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase
Aliases VHL1; von Hippel-Lindau syndrome; von Hippel-Lindau tumor suppressor; RCA11; pVHL; elongin binding protein; ......
Chromosomal Location3p25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of VHL. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolVHL
Namevon Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase
Aliases VHL1; von Hippel-Lindau syndrome; von Hippel-Lindau tumor suppressor; RCA11; pVHL; elongin binding protein; ......
Chromosomal Location3p25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of VHL expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolVHL
Namevon Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase
Aliases VHL1; von Hippel-Lindau syndrome; von Hippel-Lindau tumor suppressor; RCA11; pVHL; elongin binding protein; ......
Chromosomal Location3p25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between VHL and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolVHL
Namevon Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase
Aliases VHL1; von Hippel-Lindau syndrome; von Hippel-Lindau tumor suppressor; RCA11; pVHL; elongin binding protein; ......
Chromosomal Location3p25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting VHL collected from DrugBank database.
> Drugs from DrugBank database
 

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