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 2,851–2,900 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 Y112H (c.334T>C)2
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	submitted

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 Y112N (c.334T>A)2
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	4	submitted	EID5866 This paper analyzes a large family with Von-Hippel Lindau disease. Clinical manifestations consistent with VHL were found in 13 members of this family and all 5 affected family members who were genet… (full text at CIViC) PMID 10533030 · Bradley et al., 1999 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID5396 A previous study of 26 Japanese, VHL families was extended to 41 additional families. Germline mutations were detected in 55 of 77 Japanese families. Missense mutations within the elongin binding doma… (full text at CIViC) PMID 10761708 · Yoshida et al., 2000 · Open in CIViC	civic

VHL Y112N (c.334T>A)2

(predisposing)

Von Hippel-Lindau DiseaseUNRESOLVED

Predisposing

Supports Uncertain Significance

submitted

EID5866

This paper analyzes a large family with Von-Hippel Lindau disease. Clinical manifestations consistent with VHL were found in 13 members of this family and all 5 affected family members who were genet… (full text at CIViC)

PMID 10533030 · Bradley et al., 1999 · Open in CIViC

VHL Y156* (c.468T>G)6
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID5299 Screening of 92 unrelated patients with VHL disease revealed 61 DNA variants. No variants were found in 96 control cases. This mutation was found in a VHL type 1 patient (patient no. V41). This study … (full text at CIViC) PMID 9829912 · Olschwang et al., 1998 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID6105 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	N/A N/A	3	submitted	EID9112 12 patients with supratentorial hemangioblastoma were studied at Le Kremlin-Bicêtre University. Other phenotypes included: 6 patients with pancreatic cysts, 1 patient with an endocrine pancreatic tumo… (full text at CIViC) PMID 20647972 · Peyre et al., 2010 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID9994 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	EID10463 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.Y156* (c.468T>G) germline var… (full text at CIViC) PMID 15300849 · Gallou et al., 2004 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	2	submitted	EID6328 Eleven RCCs and 16 renal cysts from eight patients with VHL were analyzed. All patients had known germline VHL mutations. One male patient had a germline missense mutation (c.486T>G; p.Y156*) in the V… (full text at CIViC) PMID 15709172 · Lee et al., 2005 · Open in CIViC	civic

VHL Y156H (c.466T>C)2
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	2	submitted	EID8731 202 pheochromocytomas/paragangliomas, including 75 hereditary tumors, were analyzed using expression profiling, BAC array comparative genomic hybridization and somatic mutation screening. The authors … (full text at CIViC) PMID 21784903 · Burnichon et al., 2011 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	2	submitted	EID8817 A study investigated paraganglioma/pheochromocytoma tumors in a retrospective cohort and a prospective cohort. Some of these tumors were found with germline VHL mutations. Tumour ID 46 was bilateral P… (full text at CIViC) PMID 31383958 · Favier et al., 2020 · Open in CIViC	civic

VHL Y175* (c.525C>A)8
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID9545 Among patients prospectively followed by the members of the French VHL Study Group, 35 consecutive patients with well-documented endocrine pancreatic tumour (20 women and 15 men; median age,37 [21Y-57… (full text at CIViC) PMID 18580449 · Corcos et al., 2008 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID9980 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	EID10475 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.Y175* (c.525C>A) 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	EID10799 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	3	submitted	EID10917 This study was designed to characterize the endothelium of VHL patients through transcriptomic analysis of blood outgrowth endothelial cells (BOECs). BOECs were derived from peripheral blood of 5 VHL … (full text at CIViC) PMID 34571962 · de Rojas-P et al., 2021 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	submitted	EID5216 In a study of 426 unrelated VHL patients, 111 were discovered to have alterations in the VHL gene. 18 novel variants were identified in VHL patients, but none were present in 200 unaffected control in… (full text at CIViC) PMID 21463266 · Leonardi et al., 2011 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	2	accepted	EID6621 Patients with ELSTs were identified and included in the International Endolymphatic Sac Tumor Registry. The registry contained 93 patients as of July 2014, and of those, 25 were sporadic, and 68 assoc… (full text at CIViC) PMID 25867206 · Bausch et al., 2016 · Open in CIViC	civic
(oncogenic)	Clear Cell Renal Cell Carcinoma	Oncogenic	C	Supports Oncogenicity	1	submitted	EID6166 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