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 2,651–2,700 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 V166F (c.496G>T)16
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	4	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 V166fs (c.498delC)1
(oncogenic)	Clear Cell Renal Cell Carcinoma	Oncogenic	C	Supports Oncogenicity	1	submitted	EID6162 This study analyzed tumor and non-tumor kidney tissue from 195 unrelated patients with sporadic clear cell renal cell carcinoma (CCRCC) for a relationship between VHL variants in sporadic CCRCC and 'g… (full text at CIViC) PMID 11505222 · Gallou et al., 2001 · Open in CIViC	civic

VHL V166fs (c.498delC)1

(oncogenic)

Clear Cell Renal Cell Carcinoma

Oncogenic

Supports Oncogenicity

submitted

EID6162

This study analyzed tumor and non-tumor kidney tissue from 195 unrelated patients with sporadic clear cell renal cell carcinoma (CCRCC) for a relationship between VHL variants in sporadic CCRCC and 'g… (full text at CIViC)

PMID 11505222 · Gallou et al., 2001 · Open in CIViC

VHL V166SFS*4 (c.496_506del)2
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	B	Supports Predisposition	3	submitted	EID9387 A cohort of VHL patients from the Greater Toronto Area in Canada were retrospectively reviewed. Patient ID 44 was found with this germline mutation and CNS hemangioblastoma and renal cell carcinoma, W… (full text at CIViC) PMID 31368132 · Salama et al., 2019 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID9373 20 vHL families were retrospectively identified in SickKids Genetics and Cancer Genetics Program SHIRE genetics database, with data entered between 30 August 1984 and 8 August 2016. Family 17 was foun… (full text at CIViC) PMID 29437867 · Aronoff et al., 2018 · Open in CIViC	civic

VHL V170A (c.509T>C)2
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID6760 150 index patients with pheochromocytoma/paraganglioma were evaluated. Phenotypic data were collected and germline mutations in five susceptibility genes (RET, VHL, SDHB, SDHD and SDHC) were tested. A… (full text at CIViC) PMID 27539324 · Pandit et al., 2016 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID6786 Medical records of 31 genetically proven VHL patients with pheochromocytoma/paraganglioma were studied. A 30 year old Asian Indian male presented with unilateral pheochromocytoma. Genetic testing conf… (full text at CIViC) PMID 29124493 · Lomte et al., 2018 · Open in CIViC	civic

VHL V170D (c.509T>A)10
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	4	accepted	EID5863 20 patients from 6 families in the Netherlands were analyzed for Von Hippel Lindau manifestations. 1 family consisting of 12 members had the above mutation. Manifestations in this family included: ren… (full text at CIViC) PMID 9681858 · Wittebol-Post et al., 1998 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	accepted	EID5013 In a study of 138 unrelated VHL families, 109 germline mutations were found. Missense mutations were more frequently found in families with pheochromocytoma (PC). Deletions. Nonsense, and frameshift m… (full text at CIViC) PMID 8730290 · Maher et al., 1996 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	accepted	EID5029 Molecular analysis of VHL gene in 146 probands, 103 with and 43 without a positive family history, resulted in the detection of 43 germline VHL mutations. Majority of mutations were found in patients … (full text at CIViC) PMID 17661816 · Hes et al., 2007 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID5092 Germline mutation analysis of 469 VHL families reveled 300 mutations. The most common germline mutations were identified between codons 75-82, between codons 157-189 (Elongin binding domain) and at th… (full text at CIViC) PMID 8956040 · Zbar et al., 1996 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID6522 Data was collected from 82 VHL mutation carriers in the Dutch VHL surveillance program. 15 patients were found with this missense varaint in the VHL gene. The ages of the patients were represented as … (full text at CIViC) PMID 24132471 · Kruizinga et al., 2014 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID6843 A retrospective cohort study included all the VHL patients diagnosed at Peking University First Hospital (Beijing, China) prior to June 1 2016. A total of 291 patients from 115 different families were… (full text at CIViC) PMID 28388566 · Peng et al., 2017 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8446 Nine patients from a cohort of fifteen Dutch patients from five different families were found to harbour the VHL germline mutation V241D. Patient 1, a 57 year old female, presented with pancreatic cys… (full text at CIViC) PMID 9402176 · Los et al., 1997 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8959 Between 1976 and 1997, nine RCC patients from three VHL families were evaluated and treated in the University Hospital of Utrecht. Patients 1–7 were from one large family with a p.Val170Asp mutation i… (full text at CIViC) PMID 10092992 · Hes et al., 1999 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID9042 Tissue samples of renal cell carcinomas from surgical pathology specimens from four VHL patient were investigated. Germline mutations were determined from DNA in the adjacent normal kidney (for patien… (full text at CIViC) PMID 11036115 · Los et al., 2000 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID10161 All patients included in the study were VHL mutation carriers of 18 years or older examined between 1972 and 2012 in the VHL expertise centers University Medical Center Groningen (UMCG) and University… (full text at CIViC) PMID 31087189 · van der Horst-Schrivers et al., 2019 · Open in CIViC	civic

VHL V170F (c.508G>T)2
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	accepted	EID4982 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	EID8130 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