TISIDB

Summary
Symbol	VHL
Name	von 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 Location	3p25.3
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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

> KEGG and Reactome Pathway

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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
Symbol	VHL
Name	von 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 Location	3p25.3
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

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Literatures describing the relation between VHL and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28235946	Clear Cell Renal Cell Carcinoma	Promote immunity	Vascular 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.
26707870	Clear Cell Renal Cell Carcinoma	Promote 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.
21258414	Kidney Neoplasm	Promote immunity	The 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
Symbol	VHL
Name	von 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 Location	3p25.3
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

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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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	Second most enriched score: 0.85	Sensitive to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	VHL
Name	von 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 Location	3p25.3
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.357	0.118
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.513	0.781
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.249	0.865
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.302	0.318
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.459	0.824
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.106	0.968
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.023	0.952
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.266	0.875
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.201	0.912
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.205	0.855
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.016	0.503
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.141	0.0403

> Mutation difference between responders and non-responders

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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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	81.8	53.8	28	0.211
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	100	100	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	60	50	10	1

Summary
Symbol	VHL
Name	von 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 Location	3p25.3
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 [ TOP ]

Summary
Symbol	VHL
Name	von 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 Location	3p25.3
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	VHL
Name	von 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 Location	3p25.3
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	VHL
Name	von 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 Location	3p25.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of VHL expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	VHL
Name	von 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 Location	3p25.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between VHL and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	VHL
Name	von 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 Location	3p25.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting VHL collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

Browse VHL