Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

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
RET
SDHB
SDHD
TMEM127
VHL
Familial erythrocytosis 2
VHL

References:

1.

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

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2.

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

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3.

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

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4.

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

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5.

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

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6.

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

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7.

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

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8.

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

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9.

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.

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10.

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.

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11.

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

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12.

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

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13.

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

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14.

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

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15.

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

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16.

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

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17.

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

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18.

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.

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19.

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

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20.

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

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21.

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.

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22.

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

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23.

TISHERMAN SE et al. (1962) Familial pheochromocytoma.

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24.

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.

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25.

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

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26.

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

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27.

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

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28.

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.

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29.

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

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30.

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

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31.

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

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32.

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

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33.

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.

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34.

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

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35.

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

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36.

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

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37.

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

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38.

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

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39.

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

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40.

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

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41.

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

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42.

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

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43.

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

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44.

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.

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45.

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

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46.

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

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47.

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

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48.

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

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49.

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

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50.

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

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51.

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

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52.

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.

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53.

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.

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54.

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

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55.

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

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56.

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

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57.

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

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58.

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

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59.

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

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60.

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

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61.

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

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62.

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

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63.

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

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64.

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

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65.

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

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66.

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

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67.

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

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68.

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

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69.

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

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70.

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

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71.

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

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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.

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73.

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

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74.

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

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75.

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

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76.

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

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77.

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

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78.

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

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79.

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

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80.

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

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81.

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

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82.

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

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83.

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

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84.

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

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85.

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

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86.

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

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87.

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

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88.

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

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89.

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

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90.

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

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91.

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

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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.

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93.

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

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94.

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

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95.

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

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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.

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97.

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

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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.

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99.

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

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100.

NCBI article

NCBI 7428 [^]
101.

OMIM.ORG article

Omim 608537 [^]
102.

Orphanet article

Orphanet ID 120467 [^]
103.

Wikipedia article

Wikipedia EN (Von_Hippel–Lindau_tumor_suppressor) [^]
Update: April 29, 2019