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 2,401–2,450 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 Single Allele Deletion1
(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 Splice Region (c.340+1_340+5del)1
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	submitted	EID10634 Screening of 92 unrelated patients with VHL disease revealed 61 DNA variants. No variants were found in 96 control cases. Direct sequencing on peripheral blood was systematically performed on exon 1 P… (full text at CIViC) PMID 9829912 · Olschwang et al., 1998 · Open in CIViC	civic

VHL Splice Region (c.340+1_340+5del)1

(predisposing)

Von Hippel-Lindau DiseaseUNRESOLVED

Predisposing

Supports Predisposition

submitted

EID10634

Screening of 92 unrelated patients with VHL disease revealed 61 DNA variants. No variants were found in 96 control cases. Direct sequencing on peripheral blood was systematically performed on exon 1 P… (full text at CIViC)

PMID 9829912 · Olschwang et al., 1998 · Open in CIViC

VHL Splice Region (c.340+5G>C)11
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID5004 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	EID5333 14 Chinese patients from 10 families were diagnosed with Von Hippel-Lindau disease based on clinical criteria. Genetic testing demonstrated 4 members of a single family harbored the above mutation. Cl… (full text at CIViC) PMID 20518900 · Zhou et al., 2010 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID6818 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	Supports Uncertain Significance	3	submitted	EID6869 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	3	submitted	EID7721 Of 46 cases of RCC in patients younger than 25 years, one patient (case 45) was found to harbour a germline VHL splicing mutation G>C at position 553+5. Genomic DNA was extracted, using DNeasy Blood a… (full text at CIViC) PMID 20034980 · Rao et al., 2011 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8613 Genotype-phenotype correlations of 573 VHL patients from 200 kindreds were analyzed. Higher risk of pheochromocytoma was associated with missense mutations that result in substitution of a surface ami… (full text at CIViC) PMID 17024664 · Ong et al., 2007 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID9937 The proband and his nephew are found to have a splice site mutation, c.340+5G>C, of the VHL gene. The proband (age: 45, sex: male) has a history of bilateral retinal angiomas, multifocal cerebellar he… (full text at CIViC) PMID 27069690 · Arunachal et al., 2016 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	accepted	EID5246 Germline mutation analysis of seven east-Chinese families revealed 6 mutations. This splice-site alteration was found in two VHL type 2A female family members with hemangioblastomas of the central ner… (full text at CIViC) PMID 21972040 · Huang et al., 2012 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	submitted	EID5661 This study examined 182 patients with non-syndromic pheochromocytoma or paraganglioma for the presence of VHL mutations. VHL mutations were found in 3 of the 182 patients. The above mutation was found… (full text at CIViC) PMID 22438210 · Eisenhofer et al., 2012 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	submitted	EID10658 This study screened for VHL and RET mutations in a group of patients taken from the European-American Pheochromocytoma-Paraganglioma and German von Hippel-Lindau Disease Registries. The patients were … (full text at CIViC) PMID 19906784 · Erlic et al., 2010 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	1	submitted	EID5664 A case report of a 55-year-old man presenting with squamous cell carcinoma of the tongue is described. Molecular analysis of peripheral blood confirmed the presence of the above mutation. PMID 22462637 · Asakawa et al., 2012 · Open in CIViC	civic

VHL Splice Region (c.463+3A>G)4
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID5697 This paper analyzed the VHL gene of 21 patients who had clinical a clinical diagnosis of VHL, familial pheochromocytoma, or sporadic pheochromocytoma. 7 patients were from 3 families, while the remain… (full text at CIViC) PMID 23397066 · Ebenazer et al., 2013 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8220 41 non-related patients with retinal angiomatosis presenting in the Benjamin Franklin University Eye Clinic between 1988 to 1999 Germany were evaluated for the presence of other VHL lesions. VHL disea… (full text at CIViC) PMID 11148816 · Kreusel et al., 2000 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID9061 Forty-four of the 50 patients with pheochromocytoma and paraganglioma treated at the Christian Medical College, Vellore between January 2010 and June 2012 were included in this study. Four patients we… (full text at CIViC) PMID 24735130 · Pai et al., 2014 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	submitted	EID5572 A case report of an Indian female patient presenting with bilateral pheochromocytoma, and pancreatic neuroendocrine tumor at 18 years of age. Family history showed 3 family members who were likely aff… (full text at CIViC) PMID 22145147 · Boaz et al., 2011 · Open in CIViC	civic

VHL Splice Region (c.463+8C>T)3
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID9536 200 patients with intracranial aneurysms were molecularly analyzed for VHL to determine if it is a candidate gene for aneurysm formation using peripheral blood. One patient was analyzed in detail and … (full text at CIViC) PMID 23434161 · Klingler et al., 2013 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	submitted	EID5439 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
〃	Adrenal Gland Pheochromocytoma	Predisposing	C	Supports Uncertain Significance	2	accepted	EID6108 Screening of 68 patients, who had been operated on for apparently sporadic pheochromocytomas, for germline mutations in the VHL gene. This splice variant causes a premature stop codon at amino acid 66… (full text at CIViC) PMID 9663592 · van der Harst et al., 1998 · Open in CIViC	civic

VHL Splice Site (c.340+1G>T)3
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID5604 64 VHL patients with renal involvement were analyzed. 61 of the 64 patients had a known germline mutation. The above mutation was found in 2 patients. Clinical manifestations included renal cell carci… (full text at CIViC) PMID 22156657 · Jilg et al., 2012 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID7734 Ten members (7 male, 3 female) of 3 generations (2 grandparents, 2 parents and 6 children) of an Arabic-Persian family from Kwuait, of which 1 was clinically diagnosed with VHL disease, were recruited… (full text at CIViC) PMID 15467305 · Alfadhli et al., 2004 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	2	submitted	EID6487 A family study indicated the presence of VHL mutation in a Kuwaiti family with Arab parentage. 10 family members were recruited, of which 1 was clinically diagnosed with VHL disease. Four children in … (full text at CIViC) PMID 15467305 · Alfadhli et al., 2004 · Open in CIViC	civic