Gene

VHL

von Hippel-Lindau tumor suppressor

Explore in graph →CI-GENE-00038379HGNC:12687 ENSG00000134086 NCBI 7428 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (2,994)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 2,101–2,150 of 2,994 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
VHL R177* (c.529A>T)2
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted

Cohorts

Alteration frequency by cohort (42)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

gdcObserved42 cohort rows · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Kidney Renal Clear Cell Carcinoma TCGA-KIRC	Clear Cell Renal Cell Carcinoma	Ssm

Literature

Linked publications (98)

25 per page, newest first.

pubmedPublishedShowing 1–25 of 98 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Integrated molecular analysis of clear-cell renal cell carcinoma.
· Nat Genet · 2013 · PMID 23797736 · validated civic_curation pubmed
Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma.
· Int J Cancer · 2008 · PMID 18464292 · validated civic_curation pubmed
Prognostic and predictive value of VHL gene alteration in renal cell carcinoma: a meta-analysis and review.
· Oncotarget · 2017 · PMID 28103578 · validated civic_curation pubmed
Randomized Open-Label Phase II Trial of Apitolisib (GDC-0980), a Novel Inhibitor of the PI3K/Mammalian Target of Rapamycin Pathway, Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma.
· J Clin Oncol · 2016 · PMID 26951309

VHL R177fs (c.528del)5
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID5167 Genotype-phenotype correlations of 573 VHL patients from 200 kindreds were analyzed. Age-related risks of retinal hemangioblastomas and renal cell carcinoma were higher in patients with nonsense or fr… (full text at CIViC) PMID 17024664 · Ong et al., 2007 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID5622 64 VHL patients with renal involvement were analyzed. 61 of the 64 patients had a known germline mutation. The above mutation was found in 1 patient. More specifically, the above mutation is believed … (full text at CIViC) PMID 22156657 · Jilg et al., 2012 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	accepted	EID5643 An investigation of 94 VHL patients without large deletions for intragenic mutations revealed 40 different mutations in 55 unrelated individuals. In all patients with multiple affected family members … (full text at CIViC) PMID 7987306 · Crossey et al., 1994 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8141 33 patients diagnosed with VHL disease, according to (Maher et al. 1990), were tested for germline VHL mutations. Genetic testing was performed on high-molecular-weight DNA from peripheral blood using… (full text at CIViC) PMID 9106522 · Prowse et al., 1997 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	rejected	EID8142 33 patients diagnosed with VHL disease, according to (Maher et al. 1990), were tested for germline VHL mutations. Genetic testing was performed on high-molecular-weight DNA from peripheral blood using… (full text at CIViC) PMID 9106522 · Prowse et al., 1997 · Open in CIViC	civic

VHL R177fs (c.528del)5

(predisposing)

Von Hippel-Lindau DiseaseUNRESOLVED

Predisposing

Supports Predisposition

accepted

EID5167

Genotype-phenotype correlations of 573 VHL patients from 200 kindreds were analyzed. Age-related risks of retinal hemangioblastomas and renal cell carcinoma were higher in patients with nonsense or fr… (full text at CIViC)

PMID 17024664 · Ong et al., 2007 · Open in CIViC

VHL R200W (c.598C>T)16
(predisposing)	Chuvash PolycythemiaUNRESOLVED	Predisposing	B	Supports Predisposition	3	submitted	EID8250 This is a cross-sectional observational study of 120 adult and pediatric VHL(R200W) homozygotes and 31 controls at outpatient facilities in Chuvashia, Russian Federation. All VHL R200W homozygous has … (full text at CIViC) PMID 21993671 · Sable et al., 2012 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	4	submitted	EID5763 This study reports 1,548 germline and somatic mutations from 945 VHL families. This mutation was found in a homozygous patient with congenital polycythemia (case no. 37784). ACMG evidence codes: 'PP2'… (full text at CIViC) PMID 20151405 · Nordstrom-O'Brien et al., 2010 · Open in CIViC	civic
〃	Chuvash PolycythemiaUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8238 This study is conducted in Campania region in South Italy. 22 patients from 13 families with suspected Chuvash-like congenital polycythemia were included. 11 patients were from 2 unrelated families, 8… (full text at CIViC) PMID 16210343 · Perrotta et al., 2006 · Open in CIViC	civic
〃	Chuvash PolycythemiaUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8463 A comparitive study regarding the prevelance of anemia in individuals with VHL wild-type alleles (N=44) and individuals presenting the R200W VHL germline mutation(N=34) was conducted in Chuvashia, Rus… (full text at CIViC) PMID 21606165 · Miasnikova et al., 2011 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8544 188 individuals presenting with a single hemangioblastoma, no family history of VHL disease, and no evidence of retinal or abdonimal manigestations of the disease at the time of diagnosis, were invest… (full text at CIViC) PMID 17264095 · Woodward et al., 2007 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	rejected	EID9436 A study reports one family bearing two VHL gene mutations in cis (R200W and R161Q). Peripheral blood samples were taken from seven members of the family and through Sanger sequencing it was found that… (full text at CIViC) PMID 25371412 · Couvé et al., 2014 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	submitted	EID5539 Twenty individuals with Chuvash polycythemia and 51 first-degree relatives from 11 unrelated families were studied for mutations in the VHL gene. All individuals with Chuvash polycythemia carried this… (full text at CIViC) PMID 12415268 · Ang et al., 2002 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	submitted	EID5569 Of the 13 polycythemic patients analyzed, 7 were found to have VHL mutations; all 7 had both VHL alleles mutated. This missense mutation was found in 4 compound heterozygotes with polycythemia (patien… (full text at CIViC) PMID 12844285 · Pastore et al., 2003 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	2	submitted	EID5855 Case report of 5 Caucasian patients with mutations in the VHL gene and polycythemia. Patient 2, 3, and 4 described here were homozygous for the above mutation. ACMG evidence codes: 'PP2' because they … (full text at CIViC) PMID 15642680 · Bento et al., 2005 · Open in CIViC	civic
〃	Polycythemia Vera	Predisposing	C	Supports Uncertain Significance	2	submitted	EID6470 Plasma concentrations of Th1 and Th2 cytokines were analyzed using the Bio-Plex multiplex suspension array system in 34 homozygotes VHL patients, 4 heterozygous VHL patients, and 32 VHL wild-type part… (full text at CIViC) PMID 19062180 · Niu et al., 2009 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	2	submitted	EID6481 Ninety VHL R200W homozygotes and 52 controls with normal VHL alleles from Chuvashia, Russia, were studied under basal circumstances. 52 participants were female and 38 were male. The participants were… (full text at CIViC) PMID 21876117 · Gordeuk et al., 2011 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	2	submitted	EID6482 Patients with erythrocytosis from 4 families of Asian and Western European ancestry were genetically screened. This confirmed a missense mutation at c.598C > T of the VHL gene. The sample included 6 m… (full text at CIViC) PMID 12702509 · Percy et al., 2003 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	2	submitted	EID6650 DNA samples extracted from the blood of patients with idiopathic erythrocytosis were acquired from four separate idiopathic erythrocytosis databases (UK, Portugal, Germany and The Netherlands). Geneti… (full text at CIViC) PMID 27651169 · Camps et al., 2016 · Open in CIViC	civic
〃	Chuvash PolycythemiaUNRESOLVED	Predisposing	C	N/A N/A	2	submitted	EID8232 The authors identify a new VHL cryptic exon (termed E1') deep in intron 1 that is naturally expressed in many tissues. Mutations in E1' are identified in 7 families with erythrocytosis and in 1 large … (full text at CIViC) PMID 29891534 · Lenglet et al., 2018 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	1	submitted	EID5532 Eight children with a history of polycythemia and elevated serum erythropoietin level were evaluated. Three germline mutations were identified in 4 patients while, mutations were not detected for othe… (full text at CIViC) PMID 12393546 · Pastore et al., 2003 · Open in CIViC	civic
Ruxolitinib	Chuvash PolycythemiaUNRESOLVED	Predictive	C	Supports Sensitivity Response	4	accepted	EID1608 Homozygous VHL R200W mutations result in a rare congenital polycythemia known as Chuvash polycythemia. Treatment of 3 patients with this disease with the JAK1/2 inhibitor ruxolitinib led to symptomati… (full text at CIViC) PMID 27518686 · Zhou et al., 2016 · Open in CIViC	civic