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 1,251–1,300 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 N90I (c.269A>T)9
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	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 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 Null (11 kb 3' deletion)1
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID9209 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

VHL Null (11 kb 3' deletion)1

(predisposing)

Von Hippel-Lindau DiseaseUNRESOLVED

Predisposing

N/A N/A

submitted

EID9209

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

VHL Null (Complete deletion)3
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID10700 An Israeli specialized centre identified 32 VHL patients belonging to 16 different kindreds. This retrospective collection and analysis of clinical, laboratory and imaging data of VHL patients involve… (full text at CIViC) PMID 33471715 · Szalat et al., 2020 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID10973 216 patients with clinically expected VHL disease due to family history or presence of VHL typical tumours were routinely examined in an eye centre in Germany between January 2019 and January 2020, ma… (full text at CIViC) PMID 33720516 · Reich et al., 2021 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID10995 A16-year-old female patient came for genetic consultation in 2008 because genetic testing indicated the deletion of the entire VHL gene. Genetic testing was performed following the detection of multip… (full text at CIViC) PMID 32577093 · Untanas et al., 2020 · Open in CIViC	civic

VHL Null (Large deletion)10
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID5868 This study analyzed 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. One proba… (full text at CIViC) PMID 19906784 · Erlic et al., 2010 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8415 Two groups were analyzed for germline VHL mutation where Group 1 (84 individuals) presented with only one hemangioblastoma and no other clinical VHL features and those in Group 2 (4 individuals) prese… (full text at CIViC) PMID 11106358 · Hes et al., 2000 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8595 Seven VHL mutations were identified in 10 unrelated, Swedish families. A large deletion was found in family #7 with 2 affected members: both members had renal cell retinal angioma and one of the 2 als… (full text at CIViC) PMID 9452032 · Li et al., 1998 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID8994 Germline mutations in 45 unrelated Japanese VHL patients were determined from blood samples using PCR-SSCP or Southern blot analyses. The authors used the 284 codon ORF previously described by Latif e… (full text at CIViC) PMID 8634692 · 1995 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID10162 Of 65 VHL families from central Europe, 53 were identified with germline mutations using SSCP analysis of PCR products by peripheral blood. Germline rearrangements were identified in 7 families. A 2kb… (full text at CIViC) PMID 8707293 · Glavac et al., 1996 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID10188 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. 18 fa… (full text at CIViC) PMID 7728151 · Chen et al., 1995 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID10944 85 VHL patients from 34 pedigrees in 16 Chinese provinces who underwent 121 operations for Central nervous system (CNS) hemangioblastomas (HGBs) were enrolled. Surgery was performed on patients who ha… (full text at CIViC) PMID 33110457 · Liu et al., 2020 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	2	submitted	EID6326 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 large germline deletion in the VHL gene and presented w… (full text at CIViC) PMID 15709172 · Lee et al., 2005 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	accepted	EID9020 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. 6 patients were found to have the l… (full text at CIViC) PMID 20660572 · Erlic et al., 2010 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	2	submitted	EID9933 A cohort of 141 patients with hemangioblastomas of the central nervous system was analyzed. 81 patients had germline mutations in the VHL gene, analyzed through peripheral blood by Southern blotting a… (full text at CIViC) PMID 10567493 · Gläsker et al., 1999 · Open in CIViC	civic

VHL Null (Partial deletion)16
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID5804 Genetic analysis of 27 patients with urinary bladder paragangliomas, revealed 17 germline mutations, three of which were in the VHL gene. This null mutation was found in a 23-year-old female (patient … (full text at CIViC) PMID 25683602 · Martucci et al., 2015 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8405 One patient of 17 presenting with VHL germline mutations presented with a partial deletion. Single strand conformation polymorphism and southern blotting for variant identification in the DNA found in… (full text at CIViC) PMID 11309459 · Gläsker et al., 2001 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8411 Specimens were collected from a single patient for a study on second-hit deletion size in VHL gene. Samples were taken from three central nervous system hemangioblastomas, seven renal cell carcinomas … (full text at CIViC) PMID 16261628 · Gläsker et al., 2006 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8421 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	N/A N/A	3	submitted	EID8494 Of 14 patients with retinal vascular proliferation and known family history of VHL disease, 12 patients were enrolled in an approved study protocol at the National Cancer Institute. 11 of these patien… (full text at CIViC) PMID 18474773 · Wong et al., 2008 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8647 Germline mutations were found in 20 Brazilian, VHL probands and their families. A partial deletion of VHL was found in a family of 10 affected individuals. All ten family members had CNS hemangioblast… (full text at CIViC) PMID 12624160 · Rocha et al., 2003 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8714 A case report describes a a white 26Y male with hypogonadotrophic hypogonadism due to intrasellar hemangioblastoma and left retinal hemangioblastoma. PCR genetic analysis revealed a partial deletion o… (full text at CIViC) PMID 19215058 · Barton et al., 2009 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID9028 Eight patients with VHL disease type 2 were selected from the group of familial VHL patients with known VHL germline mutations followed on a clinical protocol at the Urologic Oncology Branch, National… (full text at CIViC) PMID 12114747 · Koch et al., 2002 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID9045 Nine VHL patients (3 female, 6 male; mean age, 42 years; range, 29–71 years) with pancreatic cystic lesions were selected from the group of familial VHL patients followed on the Institutional Review B… (full text at CIViC) PMID 11073821 · Mohr et al., 2000 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID10194 Clear cell RCC tumors from patients with von Hippel-Lindau disease were investigated for HIF expression. Tumours were from 4 patients with confirmed germline partial VHL deletions (patient 4 had 2 tum… (full text at CIViC) PMID 16600797 · Kim et al., 2006 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID10929 21 patients from different pedigrees of 12 Chinese provinces enrolled in this study based on a clinical and genetic diagnosis of VHL syndrome. Genetic testing was performed on genomic DNA isolated fro… (full text at CIViC) PMID 32432044 · Liu et al., 2020 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID10945 85 VHL patients from 34 pedigrees in 16 Chinese provinces who underwent 121 operations for Central nervous system (CNS) hemangioblastomas (HGBs) were enrolled. Surgery was performed on patients who ha… (full text at CIViC) PMID 33110457 · Liu et al., 2020 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	submitted	EID5662 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 Uncertain Significance	2	submitted	EID5870 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	submitted	EID6598 A prospective study followed 128 participants affected by VHL syndrome for 12 years in Padova, Italy. Individual patient data was not available, but frequency of specific mutations was presented. A pa… (full text at CIViC) PMID 26763786 · Feletti et al., 2016 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	2	submitted	EID8869 A case report of a 63Y male with multiple bilateral renal oncocytomas revealed a germline partial VHL gene deletion (unspecified). The patient had no other VHL manifestations or family history describ… (full text at CIViC) PMID 16360474 · Fiske et al., 2005 · Open in CIViC	civic

VHL Null (Partial deletion of 4.6 Kb)2
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	submitted	EID5244 A case study discussing a single patient with multiple spinal hemangioblastomas. Family history shows the patients father had a clinical diagnosis of VHL. Molecular analysis confirmed the above mutati… (full text at CIViC) PMID 19415739 · Sardi et al., 2009 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	2	submitted	EID5879 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