Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders
Moldiag Diseases Genes Support Contact

Von Hippel-Lindau tumor suppressor

As the VHL gene is a tumor suppressor, mutations cause various types of tumors both benign and malignant.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Multiplex Ligation-Dependent Probe Amplification
Turnaround 20 days
Specimen type genomic DNA

Related Diseases:

Pheochromocytoma
GDNF
KIF1B
MAX
OCLN
RET
SDHB
SDHD
TMEM127
VHL
Familial erythrocytosis 2
VHL

References:

1.

None (1997) Human cancer syndromes: clues to the origin and nature of cancer.

external link
2.

Neumann HP et al. (2002) Germ-line mutations in nonsyndromic pheochromocytoma.

external link
3.

Gemmill RM et al. (2002) The TRC8 hereditary kidney cancer gene suppresses growth and functions with VHL in a common pathway.

external link
4.

Yang H et al. (2007) pVHL acts as an adaptor to promote the inhibitory phosphorylation of the NF-kappaB agonist Card9 by CK2.

external link
5.

Vasserman NN et al. (1999) Localization of the gene responsible for familial benign polycythemia to chromosome 11q23.

external link
6.

Ang SO et al. (2002) Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia.

external link
7.

Percy MJ et al. (2003) Chuvash-type congenital polycythemia in 4 families of Asian and Western European ancestry.

external link
8.

Pastore Y et al. (2003) Mutations of von Hippel-Lindau tumor-suppressor gene and congenital polycythemia.

external link
9.

Liu E et al. (2004) The worldwide distribution of the VHL 598C>T mutation indicates a single founding event.

external link
10.

Gordeuk VR et al. (2004) Congenital disorder of oxygen sensing: association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors.

external link
11.

Cario H et al. (2005) Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene and VHL-haplotype analysis in patients with presumable congenital erythrocytosis.

external link
12.

Perrotta S et al. (2006) Von Hippel-Lindau-dependent polycythemia is endemic on the island of Ischia: identification of a novel cluster.

external link
13.

Hickey MM et al. (2007) von Hippel-Lindau mutation in mice recapitulates Chuvash polycythemia via hypoxia-inducible factor-2alpha signaling and splenic erythropoiesis.

external link
14.

Russell RC et al. (2011) Loss of JAK2 regulation via a heterodimeric VHL-SOCS1 E3 ubiquitin ligase underlies Chuvash polycythemia.

external link
15.

Maranchie JK et al. (2004) Solid renal tumor severity in von Hippel Lindau disease is related to germline deletion length and location.

external link
16.

Neumann HP et al. (1993) Pheochromocytomas, multiple endocrine neoplasia type 2, and von Hippel-Lindau disease.

external link
17.

Crossey PA et al. (1995) Molecular genetic diagnosis of von Hippel-Lindau disease in familial phaeochromocytoma.

external link
18.

van der Harst E et al. (1998) Germline mutations in the vhl gene in patients presenting with phaeochromocytomas.

external link
19.

Gallou C et al. (1999) Mutations of the VHL gene in sporadic renal cell carcinoma: definition of a risk factor for VHL patients to develop an RCC.

external link
20.

Bradley JF et al. (1999) Two distinct phenotypes caused by two different missense mutations in the same codon of the VHL gene.

external link
21.

Hoffman MA et al. (2001) von Hippel-Lindau protein mutants linked to type 2C VHL disease preserve the ability to downregulate HIF.

external link
22.

Mahon PC et al. (2001) FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity.

external link
23.

Zatyka M et al. (2002) Genetic and functional analysis of the von Hippel-Lindau (VHL) tumour suppressor gene promoter.

external link
24.

TISHERMAN SE et al. (1962) Familial pheochromocytoma.

external link
25.

Corn PG et al. (2003) Tat-binding protein-1, a component of the 26S proteasome, contributes to the E3 ubiquitin ligase function of the von Hippel-Lindau protein.

external link
26.

Neumann HP et al. (1991) Clustering of features of von Hippel-Lindau syndrome: evidence for a complex genetic locus.

external link
27.

Ong KR et al. (2007) Genotype-phenotype correlations in von Hippel-Lindau disease.

external link
28.

Nordstrom-O'Brien M et al. (2010) Genetic analysis of von Hippel-Lindau disease.

external link
29.

Maher ER et al. (1990) Statistical analysis of the two stage mutation model in von Hippel-Lindau disease, and in sporadic cerebellar haemangioblastoma and renal cell carcinoma.

external link
30.

Chen F et al. (1995) Germline mutations in the von Hippel-Lindau disease tumor suppressor gene: correlations with phenotype.

external link
31.

Brauch H et al. (1995) Von Hippel-Lindau (VHL) disease with pheochromocytoma in the Black Forest region of Germany: evidence for a founder effect.

external link
32.

Herman JG et al. (1994) Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma.

external link
33.

Crossey PA et al. (1994) Identification of intragenic mutations in the von Hippel-Lindau disease tumour suppressor gene and correlation with disease phenotype.

external link
34.

Crossey PA et al. (1994) Molecular genetic investigations of the mechanism of tumourigenesis in von Hippel-Lindau disease: analysis of allele loss in VHL tumours.

external link
35.

Latif F et al. (1993) Identification of the von Hippel-Lindau disease tumor suppressor gene.

external link
36.

Chen F et al. (1996) Genotype-phenotype correlation in von Hippel-Lindau disease: identification of a mutation associated with VHL type 2A.

external link
37.

Zbar B et al. (1996) Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan.

external link
38.

Schimke RN et al. (1998) Functioning carotid paraganglioma in the von Hippel-Lindau syndrome.

external link
39.

Maxwell PH et al. (1999) The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis.

external link
40.

Kanno H et al. (2000) Role of the von Hippel-Lindau tumor suppressor protein during neuronal differentiation.

external link
41.

Bender BU et al. (2000) Differential genetic alterations in von Hippel-Lindau syndrome-associated and sporadic pheochromocytomas.

external link
42.

Haase VH et al. (2001) Vascular tumors in livers with targeted inactivation of the von Hippel-Lindau tumor suppressor.

external link
43.

Jaakkola P et al. (2001) Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation.

external link
44.

Ivan M et al. (2001) HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.

external link
45.

Clifford SC et al. (2001) Contrasting effects on HIF-1alpha regulation by disease-causing pVHL mutations correlate with patterns of tumourigenesis in von Hippel-Lindau disease.

external link
46.

Bender BU et al. (2001) VHL c.505 T>C mutation confers a high age related penetrance but no increased overall mortality.

external link
47.

Epstein AC et al. (2001) C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation.

external link
48.

Allen RC et al. (2001) Molecular characterization and ophthalmic investigation of a large family with type 2A Von Hippel-Lindau Disease.

external link
49.

Wiesener MS et al. (2002) Paraneoplastic erythrocytosis associated with an inactivating point mutation of the von Hippel-Lindau gene in a renal cell carcinoma.

external link
50.

Richard S et al. (2002) Paradoxical secondary polycythemia in von Hippel-Lindau patients treated with anti-vascular endothelial growth factor receptor therapy.

external link
51.

Min JH et al. (2002) Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling.

external link
52.

Hon WC et al. (2002) Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHL.

external link
53.

Zatyka M et al. (2002) Identification of cyclin D1 and other novel targets for the von Hippel-Lindau tumor suppressor gene by expression array analysis and investigation of cyclin D1 genotype as a modifier in von Hippel-Lindau disease.

external link
54.

Yoshida M et al. (2002) Somatic von Hippel-Lindau disease gene mutation in clear-cell renal carcinomas associated with end-stage renal disease/acquired cystic disease of the kidney.

external link
55.

Pastore YD et al. (2003) Mutations in the VHL gene in sporadic apparently congenital polycythemia.

external link
56.

Weirich G et al. (2002) VHL2C phenotype in a German von Hippel-Lindau family with concurrent VHL germline mutations P81S and L188V.

external link
57.

Hergovich A et al. (2003) Regulation of microtubule stability by the von Hippel-Lindau tumour suppressor protein pVHL.

external link
58.

Staller P et al. (2003) Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL.

external link
59.

Wait SD et al. (2004) Somatic mutations in VHL germline deletion kindred correlate with mild phenotype.

external link
60.

Gallou C et al. (2004) Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions.

external link
61.

Gläsker S et al. (2006) Second hit deletion size in von Hippel-Lindau disease.

external link
62.

Abbott MA et al. (2006) The von Hippel-Lindau (VHL) germline mutation V84L manifests as early-onset bilateral pheochromocytoma.

external link
63.

Roe JS et al. (2006) p53 stabilization and transactivation by a von Hippel-Lindau protein.

external link
64.

Ding M et al. (2006) Loss of the tumor suppressor Vhlh leads to upregulation of Cxcr4 and rapidly progressive glomerulonephritis in mice.

external link
65.

Wang Y et al. (2007) The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development.

external link
66.

Lolkema MP et al. (2008) Allele-specific regulation of primary cilia function by the von Hippel-Lindau tumor suppressor.

external link
67.

Zehetner J et al. (2008) PVHL is a regulator of glucose metabolism and insulin secretion in pancreatic beta cells.

external link
68.

Wang Y et al. (2009) Regulation of endocytosis via the oxygen-sensing pathway.

external link
69.

Lee CM et al. (2009) VHL Type 2B gene mutation moderates HIF dosage in vitro and in vivo.

external link
70.

Mehta R et al. (2009) Proteasomal regulation of the hypoxic response modulates aging in C. elegans.

external link
71.

Sovinz P et al. (2010) Pheochromocytoma in a 2.75-year-old-girl with a germline von Hippel-Lindau mutation Q164R.

external link
72.

Neumann HP et al. (1995) Consequences of direct genetic testing for germline mutations in the clinical management of families with multiple endocrine neoplasia, type II.

external link
73.

Iliopoulos O et al. (1995) Tumour suppression by the human von Hippel-Lindau gene product.

external link
74.

Duan DR et al. (1995) Characterization of the VHL tumor suppressor gene product: localization, complex formation, and the effect of natural inactivating mutations.

external link
75.

Duan DR et al. (1995) Inhibition of transcription elongation by the VHL tumor suppressor protein.

external link
76.

Kibel A et al. (1995) Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B and C.

external link
77.

Kuzmin I et al. (1995) Identification of the promoter of the human von Hippel-Lindau disease tumor suppressor gene.

external link
78.

Loeb DB et al. (1994) A novel mutation in the von Hippel-Lindau gene.

external link
79.

Kanno H et al. (1994) Somatic mutations of the von Hippel-Lindau tumor suppressor gene in sporadic central nervous system hemangioblastomas.

external link
80.

Rubenstein JL et al. (1994) von Hippel-Lindau and the genetics of astrocytoma.

external link
81.

Gilcrease MZ et al. (1995) Somatic von Hippel-Lindau mutation in clear cell papillary cystadenoma of the epididymis.

external link
82.

Gross DJ et al. (1996) Familial pheochromocytoma associated with a novel mutation in the von Hippel-Lindau gene.

external link
83.

Zhuang Z et al. (1996) von Hippel-Lindau disease gene deletion detected in microdissected sporadic human colon carcinoma specimens.

external link
84.

None (1995) Germline mutations in the von Hippel-Lindau disease (VHL) gene in Japanese VHL. Clinical Research Group for VHL in Japan.

external link
85.

Lee S et al. (1996) Nuclear/cytoplasmic localization of the von Hippel-Lindau tumor suppressor gene product is determined by cell density.

external link
86.

Richards FM et al. (1996) Expression of the von Hippel-Lindau disease tumour suppressor gene during human embryogenesis.

external link
87.

Oberstrass J et al. (1996) Mutation of the Von Hippel-Lindau tumour suppressor gene in capillary haemangioblastomas of the central nervous system.

external link
88.

Kenck C et al. (1996) Mutation of the VHL gene is associated exclusively with the development of non-papillary renal cell carcinomas.

external link
89.

Iliopoulos O et al. (1996) Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein.

external link
90.

Garcia A et al. (1997) Molecular diagnosis of von Hippel-Lindau disease in a kindred with a predominance of familial phaeochromocytoma.

external link
91.

Gnarra JR et al. (1997) Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice.

external link
92.

Mukhopadhyay D et al. (1997) The von Hippel-Lindau tumor suppressor gene product interacts with Sp1 to repress vascular endothelial growth factor promoter activity.

external link
93.

Béroud C et al. (1998) Software and database for the analysis of mutations in the VHL gene.

external link
94.

Pause A et al. (1998) The von Hippel-Lindau tumor suppressor gene is required for cell cycle exit upon serum withdrawal.

external link
95.

Ohh M et al. (1998) The von Hippel-Lindau tumor suppressor protein is required for proper assembly of an extracellular fibronectin matrix.

external link
96.

Schoenfeld A et al. (1998) A second major native von Hippel-Lindau gene product, initiated from an internal translation start site, functions as a tumor suppressor.

external link
97.

Iliopoulos O et al. (1998) pVHL19 is a biologically active product of the von Hippel-Lindau gene arising from internal translation initiation.

external link
98.

Ivanov SV et al. (1998) Down-regulation of transmembrane carbonic anhydrases in renal cell carcinoma cell lines by wild-type von Hippel-Lindau transgenes.

external link
99.

Olschwang S et al. (1998) Germline mutation profile of the VHL gene in von Hippel-Lindau disease and in sporadic hemangioblastoma.

external link
100.

NCBI article

NCBI 7428 external link
101.

OMIM.ORG article

Omim 608537 external link
102.

Orphanet article

Orphanet ID 120467 external link
103.

Wikipedia article

Wikipedia EN (Von_Hippel–Lindau_tumor_suppressor) external link
Update: Aug. 14, 2020
Copyright © 2005-2020 by Center for Nephrology and Metabolic Disorders, Dr. Mato Nagel, MD
Albert-Schweitzer-Ring 32, D-02943 Weißwasser, Germany, Tel.: +49-3576-287922, Fax: +49-3576-287944
Sitemap | Webmail | Disclaimer | Privacy Issues