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 851–900 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 L101G (c.301_302delCTinsGG)1
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	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 26–50 of 98 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Somatostatin receptor expression on von Hippel-Lindau-associated hemangioblastomas offers novel therapeutic target.
· Sci Rep · 2017 · PMID 28094316 · validated civic_curation pubmed
Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan.
· Hum Mutat · 1996 · PMID 8956040 · validated civic_curation pubmed
Germline mutations in the von Hippel-Lindau (VHL) gene in patients from Poland: disease presentation in patients with deletions of the entire VHL gene.
· J Med Genet · 2002 · PMID 12114495 · validated civic_curation pubmed
Improved detection of germline mutations in Korean VHL patients by multiple ligation-dependent probe amplification analysis.
· J Korean Med Sci · 2009 · PMID 19270817 · validated

VHL L101G (c.301_302delinsGG)1
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	accepted	EID5040 Germline mutations were found in all 93 families that fulfilled clinical criteria of VHL disease. Mutations predicted to inactivate the VHL protein were associated with renal cell carcinoma and hemang… (full text at CIViC) PMID 9829911 · Stolle et al., 1998 · Open in CIViC	civic

VHL L101G (c.301_302delinsGG)1

(predisposing)

Von Hippel-Lindau DiseaseUNRESOLVED

Predisposing

Supports Predisposition

accepted

EID5040

Germline mutations were found in all 93 families that fulfilled clinical criteria of VHL disease. Mutations predicted to inactivate the VHL protein were associated with renal cell carcinoma and hemang… (full text at CIViC)

PMID 9829911 · Stolle et al., 1998 · Open in CIViC

VHL L101R (c.302T>G)5
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	4	submitted	EID5659 A case report of a Chinese male VHL patient presenting with multiple clear cell renal cell carcinoma at the age of 43 is described. Additional manifestations included renal and pancreatic cysts. Molec… (full text at CIViC) PMID 22398592 · Gao et al., 2012 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID5082 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 Uncertain Significance	3	submitted	EID5551 Germline mutations were found in 20 Brazilian, VHL probands and their families. This missense mutation was found in 2 affected family members with hemangioblastomas of the central nervous system (VHL … (full text at CIViC) PMID 12624160 · Rocha et al., 2003 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID6866 Medical records of 26 patients with germline mutations of the VHL gene who had been diagnosed with VHL disease in Severance Hospital (Seoul, Republic of Korea) and Samsung Medical Center (Seoul, Repub… (full text at CIViC) PMID 25078357 · Hwang et al., 2014 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	submitted	EID5790 This paper reported on a 9 member Chinese family with clinical suspicion of VHL type 1. Genetic testing was performed on all family members, and 3 were found to harbour the above mutation. Two members… (full text at CIViC) PMID 24112165 · Gao et al., 2013 · Open in CIViC	civic

VHL L116V (c.346C>G)3
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	4	accepted	EID5022 Genotype-phenotype correlations of 573 VHL patients were analyzed and confirmed that higher risk of pheochromocytoma is associated with missense mutations that result in substitution of a surface amin… (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	EID5005 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 Predisposition	2	submitted	EID5228 Mutation is seen in 8 members of a Chinese family. Molecular diagnosis is confirmed in only 3 family members, as 5 died prior to genetic testing. Manifestations in this family include CNS hemangioblas… (full text at CIViC) PMID 19133167 · Mao et al., 2009 · Open in CIViC	civic

VHL L118P (c.353T>C)12
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	4	accepted	EID5143 Genotype-phenotype correlations of 573 VHL patients were analyzed and confirmed that higher risk of pheochromocytoma is associated with missense mutations that result in substitution of a surface amin… (full text at CIViC) PMID 17024664 · Ong et al., 2007 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	accepted	EID4971 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	Supports Predisposition	3	submitted	EID5083 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	EID5276 Screening of 92 unrelated patients with VHL disease revealed 61 DNA variants. No variants were found in 96 control cases. This missense mutation was found in 3 VHL type 1 family members (patient no. V… (full text at CIViC) PMID 9829912 · Olschwang et al., 1998 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID5846 A study describing phenotypic and genotypic characteristics of VHL in an Indian population of 31 subjects, from 15 families diagnosed with VHL. Multi-cystic pancreas and CNS hemangioblastomas were the… (full text at CIViC) PMID 25952756 · Vikkath et al., 2015 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID8998 Germline mutations in 45 unrelated Japanese VHL patients were determined from blood samples using PCR-SSCP or Southern blot analyses. The authors reported a nucleotide deletion (i.e. 566T>C) which coi… (full text at CIViC) PMID 8634692 · 1995 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID9976 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	EID10454 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.L118P (c.353T>C) 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	EID10614 A previous study of 26 Japanese, VHL families was extended to 41 additional families. Germline mutations were detected in 55 of 77 Japanese families using SSCP, direct sequencing, and Southern Blot an… (full text at CIViC) PMID 10761708 · Yoshida et al., 2000 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	accepted	EID5435 43 unrelated VHL patients with previously sequenced VHL germline mutations and 36 suspected VHL mutation carriers were subject to denaturing high performance liquid chromatography (DHPLC) mutation scr… (full text at CIViC) PMID 11409863 · Klein et al., 2001 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	accepted	EID5477 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
(oncogenic)	Clear Cell Renal Cell Carcinoma	Oncogenic	C	Supports Oncogenicity	1	accepted	EID6905 Tumors from 98 patients with sporadic clear cell renal carcinoma (ccRC) were analyzed for VHL mutations and loss of heterozygosity (LOH). Somatic VHL variants were observed in 56 patients, and VHL LOH… (full text at CIViC) PMID 7915601 · Gnarra et al., 1994 · Open in CIViC	civic

VHL L118R (c.353T>G)2
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID5007 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 Predisposition	3	submitted	EID7738 A retrospective study of thirty-one subjects with chromaffin tumours from the St Bartholomew’s Hospital found 12 patients with VHL mutations. A germline missense mutation (c.353T>G) was found in famil… (full text at CIViC) PMID 19208735 · Srirangalingam et al., 2009 · Open in CIViC	civic