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 2,901–2,950 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 Y175* (c.525C>G)1
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	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 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 Y175* (c.525delC)1
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	accepted	EID5736 Genotype-phenotype correlations of 573 VHL patients from 200 kindreds were analyzed. Age-related risks of retinal angiomas and renal cell carcinoma were higher in patients with nonsense or frameshift … (full text at CIViC) PMID 17024664 · Ong et al., 2007 · Open in CIViC	civic

VHL Y175* (c.525delC)1

(predisposing)

Von Hippel-Lindau DiseaseUNRESOLVED

Predisposing

Supports Uncertain Significance

accepted

EID5736

Genotype-phenotype correlations of 573 VHL patients from 200 kindreds were analyzed. Age-related risks of retinal angiomas and renal cell carcinoma were higher in patients with nonsense or frameshift … (full text at CIViC)

PMID 17024664 · Ong et al., 2007 · Open in CIViC

VHL Y175C (c.524A>G)8
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID5577 Thirty-five unrelated patients suspected of having von Hippel-Lindau disease were analyzed and 32 VHL gene variants were found in 35 patients. An association of clear cell renal carcinoma development … (full text at CIViC) PMID 14722919 · Ruiz-Llorente et al., 2004 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID7133 • A 53 year old Puerto-Rican male presented with bilateral adrenal pheochromocytomas and a paracaval lymph node with a paraganglioma. He had a history of morbid obesity, obstructive sleep apnea, diabe… (full text at CIViC) PMID 30105105 · Astapova et al., 2018 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID10732 This report studied the prevalence of germline variants in Japanese PPGL patients. Of the 370 PPGL original Japanese probands, this cohort consisted of 15 patients with pheochromocytoma and/or paragan… (full text at CIViC) PMID 34439168 · Yonamine et al., 2021 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID10927 17 patients from 10 families affected with VHL syndrome, particularly with retinal capillary hemangioblastomas (RCHs) were examined. Details about this patient are not specified in the study, but pati… (full text at CIViC) PMID 34566400 · Murro et al., 2021 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	submitted	EID5747 This paper looks at 70 unrelated patients with idiopathic polycythemia and aims to identify their etiology and molecular basis. Genetic testing was performed on all patients, which examined all genes … (full text at CIViC) PMID 23859443 · Bento et al., 2013 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	2	submitted	EID5853 Case report of 5 Caucasian patients with mutations in the VHL gene and polycythemia. Patient 5 described here was a Portuguese female who was heterozygous for the above mutation. ACMG evidence codes: … (full text at CIViC) PMID 15642680 · Bento et al., 2005 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	2	submitted	EID8810 Fresh frozen (nZ69) and formalin-fixed paraffinembedded (FFPE; nZ30) specimens, including PCCs/PGLs and normal adrenal medullas (nAM), were collected by hospitals through the Spanish National Tumor Ba… (full text at CIViC) PMID 23660872 · de Cubas et al., 2013 · Open in CIViC	civic
(functional)	—UNRESOLVED	Functional	D	Does Not Support Loss Of Function	3	submitted	EID8264 The heterozygous Y175C (c.524A>G) VHL variant was found in the germline of a 53 year old male with bilateral adrenal pheochromocytomas. Wildtype (WT) and Y175C VHL were stably overexpressed in VHL-nul… (full text at CIViC) PMID 30105105 · Astapova et al., 2018 · Open in CIViC	civic

VHL Y175N (c.523T>A)3
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID5576 Thirty-five unrelated patients suspected of having von Hippel-Lindau disease were analyzed and 32 VHL gene variants were found in 35 patients. An association of clear cell renal carcinoma development … (full text at CIViC) PMID 14722919 · Ruiz-Llorente et al., 2004 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	2	submitted	EID5701 This paper describes the clinical and genetic findings of 36 Spanish pediatric patients with pheochromocytoma or paraganglioma. Genetic testing involved sequencing and MLPA of VHL, RET, SDHA, SDHB, SD… (full text at CIViC) PMID 23404858 · Cascón et al., 2013 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	2	submitted	EID8809 Fresh frozen (nZ69) and formalin-fixed paraffinembedded (FFPE; nZ30) specimens, including PCCs/PGLs and normal adrenal medullas (nAM), were collected by hospitals through the Spanish National Tumor Ba… (full text at CIViC) PMID 23660872 · de Cubas et al., 2013 · Open in CIViC	civic

VHL Y185* (c.555C>A)2
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID5690 Genetic analysis of 7 Hungarian individuals from 5 unrelated families affected with von Hippel-Lindau disease revealed 5 different mutations, 3 of which were novel. The mutations could not be found wi… (full text at CIViC) PMID 23298237 · Losonczy et al., 2013 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID10964 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

VHL Y98C (c.293A>G)11
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID5397 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
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID5844 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 lesions and CNS hemangioblastomas … (full text at CIViC) PMID 25952756 · Vikkath et al., 2015 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID6354 37 Danish patients diagnosed with VHL before 18 years from a prospective cohort study from Denmark's National vHL Research Database (Binderup et al., 2013) were assessed. One family with 1 patient (Fa… (full text at CIViC) PMID 28650583 · Launbjerg et al., 2017 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8353 A 78 year old female patient presented with a 3 year history of unstable blood pressure, headaches and chest oppression as well as a 35 year history of hypertension. She underwent a CT scan due to los… (full text at CIViC) PMID 12081237 · Arao et al., 2002 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8553 45 individuals from 5 unrelated Chinese families were evaluated, of which 21 patients were diagnosed with VHL or showed strong evidence of having this disease. In family 5, the proband was a 10 year o… (full text at CIViC) PMID 29871882 · Liu et al., 2018 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID9057 The study assessed the long-term prognosis of VHL and non-VHL patients among 110 consecutive patients with haemangioblastoma (HB) of the CNS treated between 1953 and 1993 at one neurosurgical unit. 14… (full text at CIViC) PMID 10592114 · Niemelä et al., 1999 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID9274 27 index patients suspected of having VHL disease from unrelated Chinese families and their relatives were studied. The nucleotide were numbered according to the sequence numbering by Latif et al, 199… (full text at CIViC) PMID 18446368 · Zhang et al., 2008 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	2	accepted	EID5217 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	EID6665 Information about all vHL-related examinations performed and all manifestations diagnosed throughout each Danish subject's lifetime up to the time of study inclusion was collected through detailed int… (full text at CIViC) PMID 25834951 · Binderup et al., 2016 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	2	submitted	EID8704 A cohort of 314 patients with pheochromocytoma and functional paraganglioma had blood samples collected and all five major pheo-pgl susceptibility genes (RET, VHL, SDHB, SDHD, and SDHC) were screened … (full text at CIViC) PMID 16314641 · Amar et al., 2005 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	1	submitted	EID6564 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. The … (full text at CIViC) PMID 26763786 · Feletti et al., 2016 · Open in CIViC	civic