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 651–700 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 G114C (c.340G>T)3
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	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 G114R (c.340G>C)14
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	4	submitted	EID5633 A case report of a male VHL patient presenting with retinal hemangioblastoma at the age of 15 was described. Further clinical examination revealed cerebellar hemangioblastoma and a pituitary adenoma. … (full text at CIViC) PMID 22265326 · Tudorancea et al., 2012 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID5079 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	EID5305 43 Italian patients were molecularly analyzed for Von Hippel-Lindau disease based on clinical suspicion. 2 of the 43 patients (VHL-6 and -16) were found to have the above mutation. Clinical manifestat… (full text at CIViC) PMID 19464396 · Ciotti et al., 2009 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8435 Fourty-four of 389 patients with VHL (between 1988-1999) screened positive for PNETs either by pathologic analysis of tissue specimens or by characteristic radiographic appearance on CT and MRI. VHL g… (full text at CIViC) PMID 11114638 · Libutti et al., 2000 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID9067 In a study of 114 unrelated VHL families, 85 germline mutations were found. VHL mutations were detected in affected family members, but not in unaffected family members or 96 normal individuals. This … (full text at CIViC) PMID 7728151 · Chen et al., 1995 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID9118 In a study from the National Cancer Institute, 6 unrelated VHL patients with known germline VHL mutations underwent surgery for uni- or bilateral renal lesions. The paper used legacy notation for VHL … (full text at CIViC) PMID 11284029 · Phillips et al., 2001 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID9185 301 were enrolled in a prospective clinical protocol to evaluate the natural history of vHL-associated pancreatic lesions (NCT00062166). Of these, 69 patients with pancreatic manifestations of vHL dis… (full text at CIViC) PMID 29294023 · Tirosh et al., 2018 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID9202 Of 246 patients affected with von Hippel-Lindau disease, 64 patients (26%) from 38 families had pheochromocytoma, including 33 newly diagnosed during screening studies and 31 treated before screening … (full text at CIViC) PMID 10458336 · Walther et al., 1999 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID9973 A study of 103 patients with VHL retinal manifestations and 108 patients without VHL retinal manifestations extracted from the French VHL database revealed that the number of hemangioblastomas appeare… (full text at CIViC) PMID 12202531 · Dollfus et al., 2002 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID10449 Molecular and clinical analysis of 126 French VHL families tested for renal involvement revealed 92 different mutations. 90 of these families had renal involvement. The p.R113* (c.337C>T) germline var… (full text at CIViC) PMID 15300849 · Gallou et al., 2004 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID10520 93 families examined at the Clinical Center of the National Institutes of Health (Bethesda, MD) underwent genetic testing for germline mutations of the VHL gene. Whole blood was extracted and genomic… (full text at CIViC) PMID 9829911 · Stolle et al., 1998 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID10861 Seventeen patients (age range 3–73) with VHL, including 12 probands and 5 relatives, that were observed between 2005 and 2020 were recruited for a retrospective analysis in relation to pancreatic neur… (full text at CIViC) PMID 34036514 · Penitenti et al., 2021 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	accepted	EID5476 26 VHL patients from 18 families, who had undergone a partial adrenalectomy for pheochromocytoma were retrospectively analyzed. 1 patient from a single family was confirmed to have the above mutation.… (full text at CIViC) PMID 20846682 · Benhammou et al., 2010 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	2	submitted	EID8758 56 male patients age 12 to 76 years, from 40 families with VHL were examined as part of a larger screening program for VHL. VHL mutations were identified in 16 families. Individual patient phenotype-g… (full text at CIViC) PMID 9187702 · Choyke et al., 1997 · Open in CIViC	civic

VHL G114S (c.340G>A)7
(predisposing)	Kidney CarcinomaALIAS	Predisposing	C	Supports Uncertain Significance	3	rejected	EID6902 Tumors from 110 patients with sporadic renal carcinoma were analyzed for VHL mutations and loss of heterozygosity. 56 of the 98 samples from sporadic, clear cell renal carcinoma patients were identifi… (full text at CIViC) PMID 7915601 · Gnarra et al., 1994 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8371 Of 31 Brazilian patients, four presented with the c.340G>A (p.Gly114Ser) mutation of the VHL gene. Genomic DNA was extracted and all VHL coding regions were analyzed by Sanger sequencing. MLPA was per… (full text at CIViC) PMID 31528828 · Fagundes et al., 2019 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8941 A retrospective analysis of 164 patients waiting for surgery for hemangioblastomas at Freiburg University Medical Center, Freiburg, Germany was conducted. Patient #8 (male, 42Y) was found with a germl… (full text at CIViC) PMID 23407287 · Gläsker et al., 2013 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID10793 A retrospective study described polyglobulia in 19 patients precise germline VHL mutations and with hemangioblastomas. 10 other patients followed with VHL mutations without an exact location. Patient … (full text at CIViC) PMID 30214643 · Krüger et al., 2018 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	accepted	EID5452 53 patients with a molecularly confirmed VHL mutation and a pancreatic neuroendocrine tumor were collected from the German NET-Registry and the German VHL-registry. 1 patient was found to have the abo… (full text at CIViC) PMID 20660572 · Erlic et al., 2010 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	submitted	EID5586 A father and his 5 year old son had bilateral pheochromocytomas and the same missense mutation. Older child was not presented with a genetic mutation and had no manifestation of disease. Cosegregation… (full text at CIViC) PMID 15002726 · Blanco et al., 2004 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	1	submitted	EID8578 48 patients with sporadic pheochromocytoma were reviewed. One patient was found with bilateral pheochromocytoma and a mutation (p.Gly114Ser) in the VHL gene was found in both tumours. Germline DNA was… (full text at CIViC) PMID 8825918 · Eng et al., 1995 · Open in CIViC	civic

VHL G144fs (c.431del)2
(predisposing)	Kidney CarcinomaALIAS	Predisposing	C	Supports Uncertain Significance	3	submitted	EID6917 Tumors from 110 patients with sporadic renal carcinoma were analyzed for VHL mutations and loss of heterozygosity. 56 of the 98 samples from sporadic, clear cell renal carcinoma patients were identifi… (full text at CIViC) PMID 7915601 · Gnarra et al., 1994 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	submitted	EID5342 Blood samples from 5 Japanese families revealed 4 germline mutations. This mutation causes a premature stop codon at amino acid 158 and was found in a family of 11 individuals. Three VHL patients were… (full text at CIViC) PMID 8641976 · Kanno et al., 1996 · Open in CIViC	civic