VHL - von Hippel-Lindau syndrome

Human Kidney Gene DataBase

Name

von Hippel-Lindau syndrome

Symbol

VHL

Aliases

RCA1; HRCA1; elongin binding protein

Gene Product

von Hippel-Lindau tumor suppressor isoform 2
von Hippel-Lindau tumor suppressor isoform 1

Category

CpG Methylation in Kidney Neoplasms
CpG Methylation in System Syndrom with Kidney Involvment
Deletion in Kidney Neoplasms
Deletion in System Syndrom with Kidney Involvment
LOH in Kidney Neoplasms
Mutation in Kidney Neoplasms
Mutation in System Syndrom with Kidney Involvment

UniGene

Hs.421597

Reference Sequence

mRNA: NM_198156

Protein: NP_937799

OMIM and SNP

OMIM: 608537

SNP: NCBI SNP

Locus

LocusLink: 7428

Chromosome: 3

Cytoband: 3p26-p25

UCSC Genome Map

Eesembl Genome Map

Summary

Von Hippel-Lindau syndrome (VHL) is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign tumors. A germline mutation of this gene is the basis of familial inheritance of VHL syndrome. The protein encoded by this gene is a component of the protein complex that includes elongin B, elongin C, and cullin-2, and possesses ubiquitin ligase E3 activity. This protein is involved in the ubiquitination and degradation of hypoxia-inducible-factor (HIF), which is a transcription factor that plays a central role in the regulation of gene expression by oxygen. RNA polymerase II subunit POLR2G/RPB7 is also reported to be a target of this protein. Alternatively spliced transcript variants encoding distinct isoforms have been observed.

Gene Ontology

cellular component: cytosol
cellular component: mitochondrion
cellular component: endoplasmic reticulum
cellular component: nucleus
molecular function: transcription factor binding
biological process: proteolysis and peptidolysis
biological process: negative regulation of cell proliferation
biological process: protein stabilization
biological process: negative regulation of cell cycle
biological process: response to stress
biological process: negative regulation of transcription from Pol II promoter
biological process: positive regulation of cell differentiation
biological process: cellular morphogenesis
biological process: protein ubiquitination
biological process: anti-apoptosis

Expression

EST (79 ESTs, 50 libraries)
Tissue	Breadth ?	CPM ?
brain
colon
eye
germ cell
head and neck
heart
kidney
liver
lung
mammary gland
muscle
nervous
oral cavity
ovary
placenta
prostate
skin
stomach
testis
uncharacterized tissue
vascular
whole body

Evidence

CpG Methylation in Kidney Neoplasms

Kondo K, Yao M, Yoshida M, Kishida T, Shuin T, Miura T, Moriyama M, Kobayashi K, Sakai N, Kaneko S, Kawakami S, Baba M, Nakaigawa N, Nagashima Y, Nakatani Y, Hosaka M, Cullinane CA, Ellenhorn JD, Weitzel JN, Kondo K, Yao M, Yoshida M, Kishida T, Shuin T, Miura T, Moriyama M, Kobayashi K, Sakai N, Kaneko S, Kawakami S, Baba M, Nakaigawa N, Nagashima Y, Nakatani Y, Hosaka M, Kondo K, Yao M, Yoshida M, Kishida T, Shuin T, Miura T, Moriyama M, Kobayashi K, Sakai N, Kaneko S, Kawakami S, Baba M, Nakaigawa N, Nagashima Y, Nakatani Y, Hosaka M Comprehensive mutational analysis of the VHL gene in sporadic renal cellcarcinoma: relationship to clinicopathological parameters. Genes Chromosomes Cancer 2002 May;34(1):58-68.
Kuzmin I, Geil L, Ge H, Bengtsson U, Duh FM, Stanbridge EJ, Lerman MI Analysis of aberrant methylation of the VHL gene by transgenes,monochromosome transfer, and cell fusion. Oncogene 1999 Oct 7;18(41):5672-9.
Clifford SC, Prowse AH, Affara NA, Buys CH, Maher ER, Clifford SC, Prowse AH, Affara NA, Buys CH, Maher ER, Clifford SC, Prowse AH, Affara NA, Buys CH, Maher ER Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene andallelic losses at chromosome arm 3p in primary renal cell carcinoma:evidence for a VHL-independent pathway in clear cell renal tumourigenesis. Genes Chromosomes Cancer 1998 Jul;22(3):200-9.
Glavac D, Ravnik-Glavac M, Ovcak Z, Masera A Genetic changes in the origin and development of renal cell carcinoma(RCC). Pflugers Arch 1996;431(6 Suppl 2):R193-4.
Herman JG, Latif F, Weng Y, Lerman MI, Zbar B, Liu S, Samid D, Duan DS, Gnarra JR, Linehan WM, et al., Herman JG, Latif F, Weng Y, Lerman MI, Zbar B, Liu S, Samid D, Duan DS, Gnarra JR, Linehan WM, et al. Silencing of the VHL tumor-suppressor gene by DNA methylation in renalcarcinoma. Proc Natl Acad Sci U S A 1994 Oct 11;91(21):9700-4.

CpG Methylation in System Syndrom with Kidney Involvment

Prowse AH, Webster AR, Richards FM, Richard S, Olschwang S, Resche F, Affara NA, Maher ER, Prowse AH, Webster AR, Richards FM, Richard S, Olschwang S, Resche F, Affara NA, Maher ER Somatic inactivation of the VHL gene in Von Hippel-Lindau disease tumors. Am J Hum Genet 1997 Apr;60(4):765-71.

Deletion in Kidney Neoplasms

Fogt F, Zhuang Z, Linehan WM, Merino MJ Collecting duct carcinomas of the kidney: a comparative loss ofheterozygosity study with clear cell renal cell carcinoma. Oncol Rep 1998 Jul-Aug;5(4):923-6.
Moch H, Schraml P, Bubendorf L, Richter J, Gasser TC, Mihatsch MJ, Sauter G Intratumoral heterogeneity of von Hippel-Lindau gene deletions in renalcell carcinoma detected by fluorescence in situ hybridization. Cancer Res 1998 Jun 1;58(11):2304-9.
Zhuang Z, Roth MJ, Emmert-Buck MR, Lubensky IA, Liotta LA, Solomon D, Zhuang Z, Roth MJ, Emmert-Buck MR, Lubensky IA, Liotta LA, Solomon D Detection of the von Hippel-Lindau gene deletion in cytologic specimensusing microdissection and the polymerase chain reaction. Acta Cytol 1994 Sep-Oct;38(5):671-5.
Sukosd F, Kuroda N, Beothe T, Kaur AP, Kovacs G, Sukosd F, Kuroda N, Beothe T, Kaur AP, Kovacs G Deletion of chromosome 3p14.2-p25 involving the VHL and FHIT genes inconventional renal cell carcinoma. Cancer Res 2003 Jan 15;63(2):455-7.
Ma X, Yang K, Lindblad P, Egevad L, Hemminki K, Ma X, Yang K, Lindblad P, Egevad L, Hemminki K VHL gene alterations in renal cell carcinoma patients: novel hotspot orfounder mutations and linkage disequilibrium. Oncogene 2001 Aug 30;20(38):5393-400.
Maranchie JK, Afonso A, Albert PS, Kalyandrug S, Phillips JL, Zhou S, Peterson J, Ghadimi BM, Hurley K, Riss J, Vasselli JR, Ried T, Zbar B, Choyke P, Walther MM, Klausner RD, Linehan WM Solid renal tumor severity in von Hippel Lindau disease is related togermline deletion length and location. Hum Mutat 2004 Jan;23(1):40-6.

Deletion in System Syndrom with Kidney Involvment

Pack SD, Zbar B, Pak E, Ault DO, Humphrey JS, Pham T, Hurley K, Weil RJ, Park WS, Kuzmin I, Stolle C, Glenn G, Liotta LA, Lerman MI, Klausner RD, Linehan WM, Zhuang Z Constitutional von Hippel-Lindau (VHL) gene deletions detected in VHLfamilies by fluorescence in situ hybridization. Cancer Res 1999 Nov 1;59(21):5560-4.
Richards FM, Crossey PA, Phipps ME, Foster K, Latif F, Evans G, Sampson J, Lerman MI, Zbar B, Affara NA, et al. Detailed mapping of germline deletions of the von Hippel-Lindau diseasetumour suppressor gene. Hum Mol Genet 1994 Apr;3(4):595-8.

LOH in Kidney Neoplasms

Igarashi H, Esumi M, Ishida H, Okada K, Igarashi H, Esumi M, Ishida H, Okada K Vascular endothelial growth factor overexpression is correlated with vonHippel-Lindau tumor suppressor gene inactivation in patients with sporadicrenal cell carcinoma. Cancer 2002 Jul 1;95(1):47-53.
Kondo K, Yao M, Yoshida M, Kishida T, Shuin T, Miura T, Moriyama M, Kobayashi K, Sakai N, Kaneko S, Kawakami S, Baba M, Nakaigawa N, Nagashima Y, Nakatani Y, Hosaka M, Cullinane CA, Ellenhorn JD, Weitzel JN, Kondo K, Yao M, Yoshida M, Kishida T, Shuin T, Miura T, Moriyama M, Kobayashi K, Sakai N, Kaneko S, Kawakami S, Baba M, Nakaigawa N, Nagashima Y, Nakatani Y, Hosaka M, Kondo K, Yao M, Yoshida M, Kishida T, Shuin T, Miura T, Moriyama M, Kobayashi K, Sakai N, Kaneko S, Kawakami S, Baba M, Nakaigawa N, Nagashima Y, Nakatani Y, Hosaka M Comprehensive mutational analysis of the VHL gene in sporadic renal cellcarcinoma: relationship to clinicopathological parameters. Genes Chromosomes Cancer 2002 May;34(1):58-68.
Velickovic M, Delahunt B, Storkel S, Grebem SK VHL and FHIT locus loss of heterozygosity is common in all renal cancermorphotypes but differs in pattern and prognostic significance. Cancer Res 2001 Jun 15;61(12):4815-9.
Alimov A, Kost-Alimova M, Liu J, Li C, Bergerheim U, Imreh S, Klein G, Zabarovsky ER Combined LOH/CGH analysis proves the existence of interstitial 3pdeletions in renal cell carcinoma. Oncogene 2000 Mar 9;19(11):1392-9.
Chino K, Esumi M, Ishida H, Okada K, Chino K, Esumi M, Ishida H, Okada K Characteristic loss of heterozygosity in chromosome 3P and low frequencyof replication errors in sporadic renal cell carcinoma. J Urol 1999 Aug;162(2):614-8.
Gnarra JR, Tory K, Weng Y, Schmidt L, Wei MH, Li H, Latif F, Liu S, Chen F, Duh FM, et al. Mutations of the VHL tumour suppressor gene in renal carcinoma. Nat Genet 1994 May;7(1):85-90.

Mutation in Kidney Neoplasms

Igarashi H, Esumi M, Ishida H, Okada K, Igarashi H, Esumi M, Ishida H, Okada K Vascular endothelial growth factor overexpression is correlated with vonHippel-Lindau tumor suppressor gene inactivation in patients with sporadicrenal cell carcinoma. Cancer 2002 Jul 1;95(1):47-53.
Oh RR, Park JY, Lee JH, Shin MS, Kim HS, Lee SK, Kim YS, Lee SH, Lee SN, Yang YM, Yoo NJ, Lee JY, Park WS, Oh RR, Park JY, Lee JH, Shin MS, Kim HS, Lee SK, Kim YS, Lee SH, Lee SN, Yang YM, Yoo NJ, Lee JY, Park WS Expression of HGF/SF and Met protein is associated with geneticalterations of VHL gene in primary renal cell carcinomas. APMIS 2002 Mar;110(3):229-38.
Hemminki K, Jiang Y, Ma X, Yang K, Egevad L, Lindblad P Molecular epidemiology of VHL gene mutations in renal cell carcinomapatients: relation to dietary and other factors. Carcinogenesis 2002 May;23(5):809-15.
Bodmer D, Eleveld M, Ligtenberg M, Weterman M, van der Meijden A, Koolen M, Hulsbergen-van der Kaa C, Smits A, Smeets D, Geurts van Kessel A Cytogenetic and molecular analysis of early stage renal cell carcinomas ina family with a translocation (2;3)(q35;q21). Cancer Genet Cytogenet 2002 Apr 1;134(1):6-12.
Wiesener MS, Seyfarth M, Warnecke C, Jurgensen JS, Rosenberger C, Morgan NV, Maher ER, Frei U, Eckardt KU Paraneoplastic erythrocytosis associated with an inactivating pointmutation of the von Hippel-Lindau gene in a renal cell carcinoma. Blood 2002 May 15;99(10):3562-5.
Kondo K, Yao M, Yoshida M, Kishida T, Shuin T, Miura T, Moriyama M, Kobayashi K, Sakai N, Kaneko S, Kawakami S, Baba M, Nakaigawa N, Nagashima Y, Nakatani Y, Hosaka M, Cullinane CA, Ellenhorn JD, Weitzel JN, Kondo K, Yao M, Yoshida M, Kishida T, Shuin T, Miura T, Moriyama M, Kobayashi K, Sakai N, Kaneko S, Kawakami S, Baba M, Nakaigawa N, Nagashima Y, Nakatani Y, Hosaka M, Kondo K, Yao M, Yoshida M, Kishida T, Shuin T, Miura T, Moriyama M, Kobayashi K, Sakai N, Kaneko S, Kawakami S, Baba M, Nakaigawa N, Nagashima Y, Nakatani Y, Hosaka M Comprehensive mutational analysis of the VHL gene in sporadic renal cellcarcinoma: relationship to clinicopathological parameters. Genes Chromosomes Cancer 2002 May;34(1):58-68.
Hamano K, Esumi M, Igarashi H, Chino K, Mochida J, ISHIDA And H, Okada K, Hamano K, Esumi M, Igarashi H, Chino K, Mochida J, ISHIDA And H, Okada K, Hamano K, Esumi M, Igarashi H, Chino K, Mochida J, ISHIDA And H, Okada K Biallelic inactivation of the von Hippel-Lindau tumor suppressor gene insporadic renal cell carcinoma. J Urol 2002 Feb;167(2 Pt 1):713-7.
Ma X, Yang K, Lindblad P, Egevad L, Hemminki K, Ma X, Yang K, Lindblad P, Egevad L, Hemminki K VHL gene alterations in renal cell carcinoma patients: novel hotspot orfounder mutations and linkage disequilibrium. Oncogene 2001 Aug 30;20(38):5393-400.
Gallou C, Longuemaux S, Delomenie C, Mejean A, Martin N, Martinet S, Palais G, Bouvier R, Droz D, Krishnamoorthy R, Junien C, Beroud C, Dupret JM, Gallou C, Longuemaux S, Delomenie C, Mejean A, Martin N, Martinet S, Palais G, Bouvier R, Droz D, Krishnamoorthy R, Junien C, Beroud C, Dupret JM Association of GSTT1 non-null and NAT1 slow/rapid genotypes with vonHippel-Lindau tumour suppressor gene transversions in sporadic renal cellcarcinoma. Pharmacogenetics 2001 Aug;11(6):521-35.
Eleveld MJ, Bodmer D, Merkx G, Siepman A, Sprenger SH, Weterman MA, Ligtenberg MJ, Kamp J, Stapper W, Jeuken JW, Smeets D, Smits A, Geurts Van Kessel A Molecular analysis of a familial case of renal cell cancer and at(3;6)(q12;q15). Genes Chromosomes Cancer 2001 May;31(1):23-32.
Ashida S, Okuda H, Chikazawa M, Tanimura M, Sugita O, Yamamoto Y, Nakamura S, Moriyama M, Shuin T Detection of circulating cancer cells with von hippel-lindau gene mutationin peripheral blood of patients with renal cell carcinoma. Clin Cancer Res 2000 Oct;6(10):3817-22.
Kume H, Oda H, Nakatsuru Y, Shimizu Y, Takahashi Y, Matsumoto T, Inoue T, Kameyama S, Kitamura T, Ishikawa T Genetic identification of bilateral primary or metastatic nonpapillaryrenal cell carcinoma. BJU Int 2000 Aug;86(3):208-12.
Brauch H, Weirich G, Brieger J, Glavac D, Rodl H, Eichinger M, Feurer M, Weidt E, Puranakanitstha C, Neuhaus C, Pomer S, Brenner W, Schirmacher P, Storkel S, Rotter M, Masera A, Gugeler N, Decker HJ, Brauch H, Weirich G, Brieger J, Glavac D, Rodl H, Eichinger M, Feurer M, Weidt E, Puranakanitstha C, Neuhaus C, Pomer S, Brenner W, Schirmacher P, Storkel S, Rotter M, Masera A, Gugeler N, Decker HJ VHL alterations in human clear cell renal cell carcinoma: association withadvanced tumor stage and a novel hot spot mutation. Cancer Res 2000 Apr 1;60(7):1942-8.
Yang K, Lindblad P, Egevad L, Hemminki K Novel somatic mutations in the VHL gene in Swedish archived sporadic renalcell carcinomas. Cancer Lett 1999 Jul 1;141(1-2):1-8.
Brauch H, Weirich G, Hornauer MA, Storkel S, Wohl T, Bruning T, Brauch H, Weirich G, Hornauer MA, Storkel S, Wohl T, Bruning T Trichloroethylene exposure and specific somatic mutations in patients withrenal cell carcinoma. J Natl Cancer Inst 1999 May 19;91(10):854-61.
Lemm I, Lingott A, Pogge v Strandmann E, Zoidl C, Bulman MP, Hattersley AT, Schulz WA, Ebert T, Ryffel GU, Lemm I, Lingott A, Pogge v Strandmann E, Zoidl C, Bulman MP, Hattersley AT, Schulz WA, Ebert T, Ryffel GU Loss of HNF1alpha function in human renal cell carcinoma: frequentmutations in the VHL gene but not the HNF1alpha gene. Mol Carcinog 1999 Apr;24(4):305-14.
Suzuki H, Ueda T, Komiya A, Okano T, Isaka S, Shimazaki J, Ito H Mutational state of von Hippel-Lindau and adenomatous polyposis coli genesin renal tumors. Oncology 1997 May-Jun;54(3):252-7.
Prowse AH, Webster AR, Richards FM, Richard S, Olschwang S, Resche F, Affara NA, Maher ER, Prowse AH, Webster AR, Richards FM, Richard S, Olschwang S, Resche F, Affara NA, Maher ER Somatic inactivation of the VHL gene in Von Hippel-Lindau disease tumors. Am J Hum Genet 1997 Apr;60(4):765-71.
Bruning T, Weirich G, Hornauer MA, Hofler H, Brauch H, Bruning T, Weirich G, Hornauer MA, Hofler H, Brauch H Renal cell carcinomas in trichloroethene (TRI) exposed persons areassociated with somatic mutations in the von Hippel-Lindau (VHL) tumoursuppressor gene. Arch Toxicol 1997;71(5):332-5.
Wenzel M, Enczmann J, Uhrberg M, Hernandez A, Wiese U, Ackermann R, Schmitz-Draeger B, Ebert T, Wernet P Screening for renal carcinoma associated mutations in the vonHippel-Lindau tumor suppressor gene by temperature gradient gelelectrophoresis. Electrophoresis 1997 Jan;18(1):45-51.
Zhuang Z, Gnarra JR, Dudley CF, Zbar B, Linehan WM, Lubensky IA, Zhuang Z, Gnarra JR, Dudley CF, Zbar B, Linehan WM, Lubensky IA Detection of von Hippel-Lindau disease gene mutations in paraffin-embeddedsporadic renal cell carcinoma specimens. Mod Pathol 1996 Aug;9(8):838-42.
Kenck C, Wilhelm M, Bugert P, Staehler G, Kovacs G, Kenck C, Wilhelm M, Bugert P, Staehler G, Kovacs G, Kenck C, Wilhelm M, Bugert P, Staehler G, Kovacs G Mutation of the VHL gene is associated exclusively with the development ofnon-papillary renal cell carcinomas. J Pathol 1996 Jun;179(2):157-61.
Bailly M, Bain C, Favrot MC, Ozturk M Somatic mutations of von Hippel-Lindau (VHL) tumor-suppressor gene inEuropean kidney cancers. Int J Cancer 1995 Nov 27;63(5):660-4.
Whaley JM, Naglich J, Gelbert L, Hsia YE, Lamiell JM, Green JS, Collins D, Neumann HP, Laidlaw J, Li FP, et al. Germ-line mutations in the von Hippel-Lindau tumor-suppressor gene aresimilar to somatic von Hippel-Lindau aberrations in sporadic renal cellcarcinoma. Am J Hum Genet 1994 Dec;55(6):1092-102.
Foster K, Prowse A, van den Berg A, Fleming S, Hulsbeek MM, Crossey PA, Richards FM, Cairns P, Affara NA, Ferguson-Smith MA, et al. Somatic mutations of the von Hippel-Lindau disease tumour suppressor genein non-familial clear cell renal carcinoma. Hum Mol Genet 1994 Dec;3(12):2169-73.
Shuin T, Kondo K, Torigoe S, Kishida T, Kubota Y, Hosaka M, Nagashima Y, Kitamura H, Latif F, Zbar B, et al., Shuin T, Kondo K, Torigoe S, Kishida T, Kubota Y, Hosaka M, Nagashima Y, Kitamura H, Latif F, Zbar B, et al. Frequent somatic mutations and loss of heterozygosity of the vonHippel-Lindau tumor suppressor gene in primary human renal cellcarcinomas. Cancer Res 1994 Jun 1;54(11):2852-5.
Maher ER, Yates JR, Ferguson-Smith MA Statistical analysis of the two stage mutation model in von Hippel-Lindaudisease, and in sporadic cerebellar haemangioblastoma and renal cellcarcinoma. J Med Genet 1990 May;27(5):311-4.
Ashida S, Furihata M, Tanimura M, Sugita O, Yamashita M, Miura T, Moriyama M, Shuin T, Ashida S, Furihata M, Tanimura M, Sugita O, Yamashita M, Miura T, Moriyama M, Shuin T Molecular detection of von Hippel-Lindau gene mutations in urine and lymphnode samples in patients with renal cell carcinoma: potential biomarkersfor early diagnosis and postoperative metastatic status. J Urol 2003 Jun;169(6):2089-93.
Melendez B, Rodriguez-Perales S, Martinez-Delgado B, Otero I, Robledo M, Martinez-Ramirez A, Ruiz-Llorente S, Urioste M, Cigudosa JC, Benitez J, Melendez B, Rodriguez-Perales S, Martinez-Delgado B, Otero I, Robledo M, Martinez-Ramirez A, Ruiz-Llorente S, Urioste M, Cigudosa JC, Benitez J Molecular study of a new family with hereditary renal cell carcinoma and atranslocation t(3;8)(p13;q24.1). Hum Genet 2003 Feb;112(2):178-85. Epub 2002 Nov 13.
Yoshida M, Yao M, Ishikawa I, Kishida T, Nagashima Y, Kondo K, Nakaigawa N, Hosaka M Somatic von Hippel-Lindau disease gene mutation in clear-cell renalcarcinomas associated with end-stage renal disease/acquired cystic diseaseof the kidney. Genes Chromosomes Cancer 2002 Dec;35(4):359-64.
Tsutsumi H, Miyamoto C, Furuichi Y, Yoshiike M, Nozawa S, Iwamoto T VHL tumor suppressor gene: its mutation and protein level in renal cellcarcinoma. Oncol Rep 2003 Sep-Oct;10(5):1357-61.

Mutation in System Syndrom with Kidney Involvment

Vortmeyer AO, Huang SC, Pack SD, Koch CA, Lubensky IA, Oldfield EH, Zhuang Z, Vortmeyer AO, Huang SC, Pack SD, Koch CA, Lubensky IA, Oldfield EH, Zhuang Z, Vortmeyer AO, Huang SC, Pack SD, Koch CA, Lubensky IA, Oldfield EH, Zhuang Z Somatic point mutation of the wild-type allele detected in tumors ofpatients with VHL germline deletion. Oncogene 2002 Feb 14;21(8):1167-70.
Tomita N, Moriguchi A, Yamasaki K, Taniyama Y, Kotani N, Hashiya N, Yoshida M, Yao M, Higaki J, Ogihara T A family with von Hippel-Lindau disease revealed by pheochromocytoma. Hypertens Res 2001 Jul;24(4):445-50.
Bender BU, Eng C, Olschewski M, Berger DP, Laubenberger J, Altehofer C, Kirste G, Orszagh M, van Velthoven V, Miosczka H, Schmidt D, Neumann HP VHL c.505 T>C mutation confers a high age related penetrance but noincreased overall mortality. J Med Genet 2001 Aug;38(8):508-14.
Wu Y, Nishio H, Lee MJ, Ayaki H, Hayashi A, Ooba T, Ogawa T, Sumino K Molecular genetic analysis and mutation screening of the VHL gene in aJapanese family with von Hippel-Lindau disease. Kobe J Med Sci 2000 Aug;46(4):147-53.
Yoshida M, Ashida S, Kondo K, Kobayashi K, Kanno H, Shinohara N, Shitara N, Kishida T, Kawakami S, Baba M, Yamamoto I, Hosaka M, Shuin T, Yao M Germ-line mutation analysis in patients with von Hippel-Lindau disease inJapan: an extended study of 77 families. Jpn J Cancer Res 2000 Feb;91(2):204-12.
Martin R, Hockey A, Walpole I, Goldblatt J Variable penetrance of familial pheochromocytoma associated with the vonHipple Lindau gene mutation, S68W. Mutations in brief no. 150. Online. Hum Mutat 1998;12(1):71.
Decker HJ, Neuhaus C, Jauch A, Speicher M, Ried T, Bujard M, Brauch H, Storkel S, Stockle M, Seliger B, Huber C, Decker HJ, Neuhaus C, Jauch A, Speicher M, Ried T, Bujard M, Brauch H, Storkel S, Stockle M, Seliger B, Huber C, Decker HJ, Neuhaus C, Jauch A, Speicher M, Ried T, Bujard M, Brauch H, Storkel S, Stockle M, Seliger B, Huber C Detection of a germline mutation and somatic homozygous loss of the vonHippel-Lindau tumor-suppressor gene in a family with a de novo mutation. Acombined genetic study, including cytogenetics, PCR/SSCP, FISH, and CGH. Hum Genet 1996 Jun;97(6):770-6.
Maher ER, Webster AR, Richards FM, Green JS, Crossey PA, Payne SJ, Moore AT, Maher ER, Webster AR, Richards FM, Green JS, Crossey PA, Payne SJ, Moore AT Phenotypic expression in von Hippel-Lindau disease: correlations withgermline VHL gene mutations. J Med Genet 1996 Apr;33(4):328-32.
Zbar B, Kishida T, Chen F, Schmidt L, Maher ER, Richards FM, Crossey PA, Webster AR, Affara NA, Ferguson-Smith MA, Brauch H, Glavac D, Neumann HP, Tisherman S, Mulvihill JJ, Gross DJ, Shuin T, Whaley J, Seizinger B, Kley N, Olschwang S, Boisson C, Richard S, Lips CH, Lerman M, et al. Germline mutations in the Von Hippel-Lindau disease (VHL) gene in familiesfrom North America, Europe, and Japan. Hum Mutat 1996;8(4):348-57.
Germline mutations in the von Hippel-Lindau disease (VHL) gene in JapaneseVHL. Clinical Research Group for VHL in Japan. Hum Mol Genet 1995 Dec;4(12):2233-7.
Whaley JM, Naglich J, Gelbert L, Hsia YE, Lamiell JM, Green JS, Collins D, Neumann HP, Laidlaw J, Li FP, et al. Germ-line mutations in the von Hippel-Lindau tumor-suppressor gene aresimilar to somatic von Hippel-Lindau aberrations in sporadic renal cellcarcinoma. Am J Hum Genet 1994 Dec;55(6):1092-102.
Maher ER, Yates JR, Ferguson-Smith MA Statistical analysis of the two stage mutation model in von Hippel-Lindaudisease, and in sporadic cerebellar haemangioblastoma and renal cellcarcinoma. J Med Genet 1990 May;27(5):311-4.

Other key publications related to this gene