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VHL Gene

protein-coding GIFtS: 71

GC03P010158

von Hippel-Lindau tumor suppressor
(Previous name: von Hippel-Lindau syndrome )
Symbol approved by the HUGO Gene Nomenclature Committee (HGNC) database

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc , and/or ⁷Ensembl, ⁸miRBase)
About This Section

Aliases
HRCA1 ^²
RCA1 ^²
VHL1 ^¹, ²
pVHL ^³

Descriptions
Protein G7 ^³
elongin binding protein ^²
von Hippel-Lindau syndrome ^¹
von Hippel-Lindau tumor suppressor ^²

External Ids
HGNC: 12687¹
Entrez Gene: 7428²
UniProtKB: P40337³
Ensembl: ENSG00000134086⁷

Search outside databases for aliases for VHL gene

Previous GC identifers: GC03P010112 GC03P010175

(According to Entrez Gene, Wikipedia's Gene Wiki,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

EntrezGene summary for VHL:

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. [provided by RefSeq]

UniProtKB/Swiss-Prot: VHL_HUMAN, P40337

Function: Involved in the ubiquitination and subsequent proteasomal degradation via the von

Hippel-Lindau ubiquitination complex. Seems to act as target recruitment subunit in the E3

ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic

conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and

histone deacetylases

Gene Wiki entry for VHL (Von_Hippel-Lindau_tumor_suppressor)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 36),
and/or miRBase,
Genomic Views according to UCSC and Ensembl, Transcription factor binding sites according to SABiosciences)
About This Section

Genomic View:

UCSC Golden Path with GeneCards custom track

Transcription factor binding sites upstream to the VHL gene

Entrez Gene cytogenetic band: 3p26-p25 Ensembl cytogenetic band: 3p25.3 HGNC cytogenetic band: 3p25.3

VHL Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)

GeneLoc gene densities for chromosome 3 GeneLoc Exon Structure

GeneLoc location for GC03P010158: (about GC identifiers)

Start:	10,158,319 bp from pter
End:	10,168,762 bp from pter
Size:	10,444 bases
Orientation:	plus strand

RefSeq DNA sequence:

NC_000003.10 NT_022517.17

(According to ¹UniProtKB, and/or Ensembl, Phosphorylation sites according to ²Phosphosite, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Enzo Life Sciences, Abnova, OriGene and/or, Abcam,
Biochemical Assays by Invitrogen, Millipore, R&D Systems, Cell Signaling Technology, and/or Enzo Life Sciences, Ontologies according to Gene Ontology Consortium 01 Apr 2009 and Entrez Gene, Antibodies by Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Cell Signaling Technology, Abcam, Abnova, and/or Novus Biologicals)
About This Section

UniProtKB/Swiss-Prot: VHL_HUMAN, P40337 (See protein sequence)

Recommended Name: Von Hippel-Lindau disease tumor suppressor

Size: 213 amino acids; 24153 Da

Subunit: Component of the VCB (VHL-Elongin BC-CUL2) complex; this complex acts as a

ubiquitin-ligase E3 and directs proteosome-dependent degradation of targeted proteins. Interacts

with CUL2; this interaction is dependent on the integrity of the trimeric VBC complex. Interacts

(via the beta domain) with HIF1A (via the NTAD domain); this interaction mediates degradation of

HIF1A in normoxia and, in hypoxia, prevents ubiqitination and degradation of HIF1A by mediating

hypoxia-induced translocation to the nucleus, a process which requires a hypoxia-dependent

regulatory signal. Interacts with RNF139 and UBP33. Interacts with PHF17

Subcellular location: Isoform 1: Cytoplasm. Membrane; Peripheral membrane protein. Nucleus.

Note=Found predominantly in the cytoplasm and with less amounts nuclear or membrane-associated

Subcellular location: Isoform 3: Cytoplasm. Nucleus. Note=Equally distributed between the nucleus

and the cytoplasm but not membrane-associated

PDB structures from and Proteopedia :

1LM8 (3D)

1LQB (3D)

1VCB (3D)

Secondary accessions: B2RE45 Q13599 Q6PDA9

Alternative splicing, Alternative initiation: 3 isoforms: P40337-1 P40337-2 P40337-3

Post-translational modifications:

View phosphorylation sites using PhosphoSite²

REFSEQ proteins (2 alternative transcripts):

NP_000542.1 NP_937799.1

ENSEMBL proteins:

ENSP00000256474 ENSP00000344757

Human Recombinant Proteins

	Browse Drug Discovery Central at Invitrogen for human recombinant proteins
	Browse Purified and Recombinant Proteins at Millipore
	Browse Human Recombinant Proteins at Sigma-Aldrich
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	Recombinant Proteins from Abcam (Von Hippel Lindau protein)
	Human Recombinant Proteins from Abnova (VHL)

Browse Origene for full length recombinant human proteins expressed in human HEK293 cells

5/6 Gene Ontology (GO) cellular component terms (links to tree view) (see all 6 ):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	TAS	7604013
GO:0005737	cytoplasm	IEA	--
GO:0005739	mitochondrion	NAS	12169691
GO:0005783	endoplasmic reticulum	NAS	12169691
GO:0005829	cytosol	TAS	7604013

About this table

Antibodies for VHL:

	Browse Antibodies Central at Invitrogen
	Browse Millipore's Extensive Line of Mono- and Polyclonal Antibodies
	Sigma-Aldrich Antibodies for VHL
	Browse R&D Systems for Antibodies
	Antibodies from Abcam (Von Hippel Lindau protein), each with their Abpromise^SM
	Monoclonal and Polyclonal Antibodies from Abnova (VHL)
	Novus Biologicals Antibodies for VHL

Assays for VHL:

	Browse Invitrogen for biochemical assays
	Millipore Kits and Assays for the Analysis of VHL
	Browse R&D Systems for biochemical assays
	Browse biochemical assays available from Enzo Life Sciences

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

Graphical View of Domain Structure for InterPro Entry P40337

ProtoNet protein and cluster: P40337

UniProtKB/Swiss-Prot: VHL_HUMAN, P40337

Domain: The Elongin BC complex binding domain is also known as BC-box with the consensus

[APST]-L-x(3)-C-x(3)-[AILV]

(According to MGI Jun 06 2009, UniProtKB, IUBMB,and/or Genatlas,
shRNA from OriGene, Sigma-Aldrich, RNAi from Sigma-Aldrich,
RNAi Products, Clones, and Q-PCR Products from Invitrogen, Millipore, OriGene, and/or Abnova, siRNAs from Applied Biosystems, SYBR primers from OriGene, Cell-based Assays from Millipore, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
About This Section

Inhib. RNA:		Invitrogen RNAi Products for gene knock-down (VHL)
		Browse for Gene Knock-down Tools from Millipore
		Abnova Chimera RNAi Products for Gene knock-down (VHL)

OriGene 29mer shRNA kit in GFP-retroviral vectors (see all 2): NM_000551

Applied Biosystems Silencer® siRNAs for VHL

Sigma-Aldrich siRNA and siRNA Panels for VHL

Sigma-Aldrich shRNA Panels and shRNA for VHL

Explore Sigma-Aldrich super-pooled esiRNAs

Clones:		Invitrogen Clones for VHL
		Browse Clones for the Expression of Recombinant Proteins Available from Millipore

OriGene GFP tagged cDNA clones in CMV expression vector (see all 2): NM_000551
Myc/DDK tagged cDNA clones in CMV expression vector (see all 2): NM_000551
untagged cDNA clones in CMV expression vector (see all 2): NM_000551

Primers:

Browse Quantitative PCR Central at Invitrogen for Q-PCR LUX™ Primers

OriGene genome-wide validated SYBR primer pairs: NM_000551

UniProtKB/Swiss-Prot: VHL_HUMAN, P40337

Function: Involved in the ubiquitination and subsequent proteasomal degradation via the von

Hippel-Lindau ubiquitination complex. Seems to act as target recruitment subunit in the E3

ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic

conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and

histone deacetylases

Genatlas biochemistry entry for VHL:

Tumor suppressor protein,complexing with CUL2,elongin B,elongin C Rbx/ROC1 and an ubiquitin

conjugating enzyme other than CDC34,either UBE2B,2D1,L6 or others to form an active E3 ubiquitin

ligase complex named the VCB-CUL2 complex,targetting and regulating the hypoxia inducible protein

HIF in normoxic conditions,also involved in cell cycle regulation exit of cell cycle upon serum

withdrawal and in extracellular matrix formation through interaction with fibronectin may be an

inhibitor of the transcriptor elongation factor B (SIII) through competition to binding TCEB1 and

TCEBD

15/21 MGI mutant phenotypes (inferred from 7 alleles) (MGI details for Vhl) (see all 21 ):

	cellular	craniofacial	digestive/alimentary	embryogenesis
endocrine/exocrine gland	growth/size	hematopoietic system	homeostasis/metabolism	immune system
lethality-postnatal	lethality-prenatal/perinatal	life span-post-weaning/aging	limbs/digits/tail	liver/biliary system

1 Gene Ontology (GO) molecular function term (links to tree view):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0008134	transcription factor binding	TAS	7660122

About this table

(Pathways according to Invitrogen (maps by GeneGo), Millipore, Cell Signaling Technology, Sigma-Aldrich, KEGG and/or UniProtKB,
Sets of similar genes according to GeneDecks, Proteins Network according to SABiosciences, Interactions according to ¹UniProtKB, ²MINT, and/or ³STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
About This Section

4 Sigma-Aldrich "Your Favorite Gene" Pathways for VHL (Your Favorite Gene powered by Ingenuity)

Hypoxia Signaling in the Cardiovascular System
HIF1&alpha
Protein Ubiquitination Pathway
Renal Cell Carcinoma Signaling

GeneDecks VHL for the pathways selected above

About GeneDecksing

UniProtKB/Swiss-Prot: VHL_HUMAN, P40337

Pathway: Protein modification; protein ubiquitination

Gene Network Central^TM Interacting Genes and Proteins Network for VHL

5/94 Interacting proteins for VHL (ENSP00000256474³ P40337^{1, 2}) via UniProtKB, MINT, and/or STRING (see all 94 )

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
COPS5	Q92905¹	STRING (score=.965) EBI-301246, EBI-594661
DGKI	O75912¹	STRING (score=.819) EBI-301246, EBI-1765520
NEDD8	Q15843¹	STRING (score=.824) EBI-301246, EBI-716247
RBX1	P62877¹	STRING (score=.992) EBI-301246, EBI-398523
RNF139	Q8WU17¹	STRING (score=.922) EBI-301246, EBI-1551681

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5/12 Gene Ontology (GO) biological process terms (links to tree view) (see all 12 ):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	TAS	7660122
GO:0000902	cell morphogenesis	NAS	12169691
GO:0006508	proteolysis	TAS	10353251
GO:0006916	anti-apoptosis	NAS	12169691
GO:0006950	response to stress	NAS	12169691

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(Chemical Compounds according to UniProtKB, Enzo Life Sciences, Sigma-Aldrich, Tocris Bioscience, and/or Novoseek and Drugs according to Enzo Life Sciences and/or PharmGKB)
About This Section

Browse drugs & compounds from Enzo Life Sciences

Browse Small Molecules at Sigma-Aldrich

Browse Tocris compounds for VHL
10/18 Novoseek chemical compound relationships for VHL gene (see all 18 )

Compound	Score	Articles	PubMed IDs for Articles with Shared Sentences (# sentences)
ehen	56.34	1	9290699 (1)
oxygen	51.13	64	11336512 (3), 11175344 (2), 12507560 (2), 15181450 (2) (see all 43)
proline	46.57	9	11504942 (2), 11823643 (1), 18694926 (1), 12606543 (1) (see all 8)
deferoxamine	30.36	2	15878351 (1)
cocl2	16.84	1	12925778 (1)
phosphatidylinositol	6.30	1	11585776 (1)
cobalt	6.28	4	11358837 (2), 12606543 (2)
potassium	4.07	2	12359370 (1), 12460920 (1)
calcium	1.05	1	7587388 (1)
lysine	0.00	3	16862177 (1), 15031665 (1), 11536052 (1)

About this table

1 PharmGKB drug compound relationship for VHL gene

Drug compound	PharmGKB Relations	PubMed IDs for articles supporting these relationships
bevacizumab	CO PD	12890841

About this table

(GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 219 Homo sapiens; Jun 2 2009) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView,
non coding RNAs according to RNAdb,
ESTs according to GeneTide,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from Invitrogen, Millipore, and/or Abnova,
siRNAs from Applied Biosystems, Sigma-Aldrich,
shRNA from Sigma-Aldrich, OriGene,
Tagged/untagged cDNA clones from OriGene,
Expression Assays from Applied Biosystems)
About This Section

Inhib. RNA:		Invitrogen RNAi Products for gene knock-down (VHL)
		Browse for Gene Knock-down Tools from Millipore
		Abnova Chimera RNAi Products for Gene knock-down (VHL)

OriGene 29mer shRNA kit in GFP-retroviral vectors (see all 2): NM_000551

Sigma-Aldrich siRNA and siRNA Panels for VHL

Sigma-Aldrich shRNA Panels and shRNA for VHL

Explore Sigma-Aldrich super-pooled esiRNAs

Applied Biosystems Silencer® siRNAs:

NM_000551 NM_198156

REFSEQ mRNAs for VHL gene (2 alternative transcripts):

NM_000551.2 NM_198156.1

Applied Biosystems TaqMan ® Gene Expression Assays:

NM_000551 NM_198156

               OriGene GFP tagged cDNA clones in CMV expression vector (see all 2): NM_000551
                                 Myc/DDK tagged cDNA clones in CMV expression vector (see all 2): NM_000551
                                 untagged cDNA clones in CMV expression vector (see all 2): NM_000551

Additional cDNA sequence:

AF088066.1 AK304002.1 AK309560.1 AK315799.1 BC027957.1 BC058831.1 L15409.1

10 DOTS entries:

DT.101982322 DT.87016137 DT.120922749 DT.92439090 DT.120922689 DT.100749785 DT.452953 DT.87015079

DT.95353470 DT.97778760

24/115 AceView cDNA sequences (see all 115 ):

NM_000551 NM_198156 R26242 BC027957 BQ893536 AI080062 BG548629 BG288777

R79504 BQ082340 BM975139 BF305686 CA433522 BC058831 BE786327 BX956555

AI254340 H73053 AA807967 BG422255 BI767841 L15409 CA414706 AA302681

highest scoring ESTs for VHL:

L15409 AA092531 AA302681 AA302852 AA361862 AA447136 AA447260 AA678378 AA988806 AI080062

Unigene Cluster for VHL:

Von Hippel-Lindau tumor suppressor

Hs.517792 [show with all ESTs]

Unigene Representative Sequence: NM_000551

GeneLoc Exon Structure

3 Alternative Splicing Database (ASD) splice patterns (SP) for VHL

ExUns:	1a	·	1b	·	1c	^	2	^	3	^	4
SP1:							-
SP2:							-		-
SP3:

About this scheme

ECgene alternative splicing isoforms for VHL

2 Ensembl transcripts including schematic representations:

ENST00000256474 ENST00000345392

(Experimental results according to ¹GeneNote and GNF BioGPS,
probe sets-to-genes annotations according to ²GeneAnnot , ³GeneTide , Sets of similar genes according to GeneDecks, Electronic Northern calculations according to data from UniGene (Build 219 Homo sapiens), SAGE tags according to CGAP, plus additional links to SOURCE, and/or GNF BioGPS, and/or EXPOLDB, and/or UniProtKB,
Expression Assays from Applied Biosystems )
About This Section

VHL expression in normal and diseased human tissues

Applied Biosystems TaqMan ® Gene Expression Assays for VHL

¹ / ² / ³

3 probe-sets matching VHL gene

Affymetrix probe-set	Array	# genes	Sensitivity	Specificity	Correlation	Length	Gb_Accession	Consensus	Uniqueness	Score	Rank
Affymetrix probe-set	Array	GeneAnnot data			GeneNote data		GeneTide data
1668_s_at²^{, 3}	U95-A	1	1.00	1.00	1.00	1.00	L15409	1.00	1.00	1.00	1
40871_at*²^{, 3}	U95-A	1	--	--	-0.08	0.31	X96489	0.20	1.00	0.72	1
1559227_s_at²	U133Plus2	1	1.00	1.00	--	--	--	--	--	--	--

About this table

Data from

(Publications) and GNF BioGPS
About these images
About these images

CGAP SAGE TAG: --

SOURCE GeneReport for Unigene cluster: Hs.517792
Expression variation in blood from EXPOLDB for VHL
UniProtKB/Swiss-Prot: VHL_HUMAN, P40337
Tissue specificity: Expressed in the adult and fetal brain and kidney

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD and/or ⁵MGI Jun 06 2009, with possible further links to Flybase and/or WormBase, Gene Trees according to Ensembl)
About This Section

Orthologs for VHL gene from 5/7 species (see all 7 )

Organism	Gene	Locus	Description	Human Similarity	NCBI accessions
dog (Canis familiaris)	VHL¹	--	von Hippel-Lindau tumor suppressor	89.73(n) 89.57(a)	494000 NM_001008552.1 NP_001008552.1
cow (Bos taurus)	VHL¹	--	von Hippel-Lindau tumor suppressor	85.41(n) 87.57(a)	540957 XM_613870.3 XP_613870.3
rat (Rattus norvegicus)	Vhl¹	--	von Hippel-Lindau tumor suppressor	83.52(n) 88.51(a)	24874 NM_052801.1 NP_434688.1
mouse (Mus musculus)	Vhl^{1, 5}	6 (49.45 cM)⁵	von Hippel-Lindau syndrome^{1, 5}	85.21(n)¹ 88.76(a)¹	22346¹ NM_009507.3¹ NP_033533.1¹ AA007840⁵ AF513984⁵ (see all 14)
chicken (Gallus gallus)	VHL¹	--	von Hippel-Lindau tumor suppressor	69.72(n) 67.32(a)	416117 XM_414447.2 XP_414447.2

About this table Species with no ortholog for VHL

ENSEMBL Gene Tree for VHL

(Paralogs according to ¹HomoloGene
and ²Ensembl, Pseudogenes according to ³Pseudogene.org)
About This Section

Paralogs for VHL gene

VHLL²

Pseudogenes

1 related pseudogene

(According to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, and UniProtKB, Linkage Disequilibrium by HapMap, Genotyping Reagents from Applied Biosystems)
About This Section

10/175 NCBI SNPs in VHL are shown (see all 175 )
(Click for Applied Biosystems TaqMan ® Genotyping Assay) (see all 45)

AB	SNP ID	Valid	Chr 3 pos	Sequence	Recs	AA Chg	Type	More	Recs	Allele freq	Pop	Total sample	More
AB	Genomic Data				Transcription Data				Allele Frequencies
				--	--	--		--	--				--
	rs1642742^1,2	A,C,F,H,O	10166943(-)	`TTATAT/CAAACC`	2	--	ut3¹ ese³		13		EA NA EU WA MN CSAM	1032
--	rs779803^1,2	A,C,F,H	10157562(+)	`ttaccA/Gtatga`	2	--	ng5¹ tfbs³		4		EU EA WA	412
	rs7629500^1,2	A,C,F,H	10167472(+)	`TTATAG/ATATTA`	2	--	ut3¹		4		EU EA WA	380
	rs779805^1,2	C,F,H,O	10158337(+)	`ACAACA/GGCCTA`	2	--	ut5¹ ese³		16		EU EA WA NA MN CSAM	2352
	rs3087462^1,2	A,C,F	10158455(+)	`GGGAGC/TGCGCA`	2	--	ut5¹		7		NA MN CSAM EA	586
--	rs1681668^1,2	A,C	10167709(-)	`CAGGCA/GCCTGT`	2	--	ut3¹ ese³		0	--	--	--	--
--	rs458106^1,2	C,F	10168509(+)	`tttggG/Aaagcc`	2	--	ut3¹		1		MN	184
--	rs1681669^1,2	A,C	10167672(-)	`TGAACC/TCAGGA`	2	--	ut3¹ ese³		0	--	--	--	--
--	rs1136249^1,2	C,F	10168683(+)	`gaggcG/Tgcagt`	2	--	ut3¹		1		MN	184
--	rs779804^1,2	C,F	10158274(+)	`AGGGGT/CGAAAA`	2	--	ng5¹		5		MN CSAM EA	408

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HapMap Linkage Disequilibrium images for VHL (up to first 250kb)

(in which this Gene is Involved, According to OMIM, UniProtKB, Novoseek, PharmGKB, Genatlas, GeneTests, Blood group antigen gene mutations by BGMUT, HGMD, GAD, HuGE Navigator, BCGD, and/or TGDB.)
About This Section

OMIM: 608537

UniProtKB/Swiss-Prot: VHL_HUMAN, P40337

Defects in VHL are a cause of pheochromocytoma [MIM:171300]. The pheochromocytomas are

catecholamine-producing, chromaffin tumors that arise in the adrenal medulla in 90% of cases. In

the remaining 10% of cases, they develop in extra-adrenal sympathetic ganglia and may be referred

to as "paraganglioma." Pheochromocytoma usually presents with hypertension. Approximately 10% of

pheochromocytoma is hereditary. The genetic basis for most cases of non-syndromic familial

pheochromocytoma is unknown

Defects in VHL are the cause of von Hippel-Lindau disease (VHLD) [MIM:193300]. VHLD is a

dominantly inherited familial cancer syndrome characterized by the development of retinal

angiomatosis, cerebellar and spinal hemangioblastoma, renal cell carcinoma (RCC),

phaeochromocytoma and pancreatic tumors. VHL type 1 is without pheochromocytoma, type 2 is with

pheochromocytoma. VHL type 2 is further subdivided into types 2A (pheochromocytoma, retinal

angioma, and hemangioblastomas without renal cell carcinoma and pancreatic cyst) and 2B

(pheochromocytoma, retinal angioma, and hemangioblastomas with renal cell carcinoma and pancreatic

cyst). VHL type 2C refers to patients with isolated pheochromocytoma without hemangioblastoma or

renal cell carcinoma. The estimated incidence is 3/100000 births per year and penetrance is 97% by

age 60 years

Defects in VHL are the cause of erythrocytosis familial type 2 (ECYT2) [MIM:263400]; also

called VHL-dependent polycythemia or Chuvash type polycythemia. ECYT2 is an autosomal recessive

disorder characterized by an increase in serum red blood cell mass, hypersensitivity of erythroid

progenitors to erythropoietin, increased erythropoietin serum levels, and normal oxygen affinity.

Patients with ECYT2 carry a high risk for peripheral thrombosis and cerebrovascular events

Defects in VHL are a cause of renal cell carcinoma type 1 (RCC1) [MIM:144700]; also called

hypernephroma or adenocarcinoma of kidney. Familial renal cell carcinoma syndromes form a group of

diseases characterized by a predisposition to development of renal cell carcinomas (RCCs) with

various histological subtypes

10/79 Novoseek disease relationships for VHL gene (see all 79 )

Disease	Score	Articles	PubMed IDs for Articles with Shared Sentences (# sentences)
renal clear cell carcinoma	93.23	77	18660794 (5), 15062033 (3), 17255293 (3), 18464292 (2) (see all 48)
von hippel-lindau disease	92.59	71	11309459 (3), 9156047 (2), 10567493 (2), 12584999 (2) (see all 54)
carcinoma renal cell	89.39	214	11792959 (7), 10475065 (3), 15386385 (3), 8758207 (3) (see all 99)
hemangioblastoma	87.51	44	9458097 (4), 9787178 (3), 9370235 (3), 16869749 (2) (see all 22)
renal cancer	83.88	40	12169691 (2), 18389622 (2), 9820032 (1), 15180922 (1) (see all 27)
cancer syndromes hereditary	82.77	12	11331612 (1), 10823831 (1), 12209156 (1), 16585181 (1) (see all 8)
pheochromocytoma	82.72	122	12673678 (7), 15883705 (4), 17102081 (4), 9156047 (3) (see all 59)
paraganglioma	76.68	23	16001332 (1), 16098460 (1), 15988378 (1), 10589785 (1) (see all 13)
tumors	72.70	576	12359370 (5), 15771820 (5), 10852497 (5), 12937142 (4) (see all 99)
multiple endocrine neoplasia	69.17	14	15988378 (1), 17121518 (1), 12584999 (1), 11494117 (1) (see all 11)

About this table

2 PharmGKB disease relationships for VHL gene

Disease	PharmGKB Relations	PubMed IDs for articles supporting these relationships
Carcinoma, Renal Cell	CO PD	12890841
Kidney Neoplasms	CO PD	12890841

About this table

GeneTests: VHL

Von Hippel-Lindau Syndrome

Human Gene Mutation Database: VHL
Genetic Association Database: VHL
Human Genome Epidemiology Navigator: VHL (29 documents)
Tumor Gene Database: VHL

(Possibly Related Articles in Doctor's Guide)
About This Section

(in PubMed. Associations of this gene to articles via ¹Novoseek, ²HGNC, ³Entrez Gene, ⁴UniProtKB/Swiss-Prot, ⁵UniProtKB/TrEMBL, ⁶GAD, and/or ⁷PharmGKB)
About This Section

10/714 PubMed articles for VHL gene (see all 714 ):

Mutations of von Hippel-Lindau tumor-suppressor gene and congenital polycythemia. (PubMed id 12844285)^{1, 3, 4, 6} Pastore Y.D.... Prchal J.T. (2003)
Germ-line mutations in nonsyndromic pheochromocytoma. (PubMed id 12000816)^{1, 3, 4, 6} Neumann H.P.H.... Eng C. (2002)
A second major native von Hippel-Lindau gene product, initiated from an internal translation start site, functions as a tumor suppressor. (PubMed id 9671762)^{1, 2, 3, 4} Schoenfeld A.... Burk R.D. (1998)
Phenotypic expression in von Hippel-Lindau disease: correlations with germline VHL gene mutations. (PubMed id 8730290)^{1, 3, 4} Maher E.R.... Moore A.T. (1996)
The von Hippel-Lindau tumor suppressor stabilizes novel plant homeodomain protein Jade-1. (PubMed id 12169691)^{1, 3, 4} Zhou M.I....Cohen H.T. (2002)
Hypertension, antihypertensives and mutations in the Von Hippel-Lindau gene in renal cell carcinoma: results from the Netherlands Cohort Study. (PubMed id 16208141)^{1, 3, 6} Schouten L.J....van den Brandt P.A. (2005)
Ubiquitination of a novel deubiquitinating enzyme requires direct binding to von Hippel-Lindau tumor suppressor protein. (PubMed id 11739384)^{1, 3, 4} Li Z.... Wu G. (2002)
Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B and C. (PubMed id 7660130)^{1, 3, 4} Kibel A.... Kaelin W.G. Jr. (1995)
Congenital disorder of oxygen sensing: association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors. (PubMed id 14726398)^{1, 3, 6} Gordeuk V.R....Polyakova L.A. (2004)
The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins. (PubMed id 9122164)^{1, 3, 4} Pause A....Klausner R.D. (1997)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, and/or H-InvDB)
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Entrez Gene: 7428	HGNC: 12687	AceView: VHL	Ensembl:ENSG00000134086	euGenes: HUgn7428
ECgene: VHL	H-InvDB: VHL

(According to HUGE)
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(According to ATLAS, HORDE, IMGT, MTDB, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
ATLAS Chromosomes in Cancer entry for VHL	Genetics and Cytogenetics in Oncology and Haematology
GeneReviews	http://www.genetests.org/query?gene=VHL

Licensable Technologies for VHL
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(Reagents available from Applied Biosystems, Antibodies and assays by Cell Signaling Technology, Abcam, Novus Biologicals,
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Products for VHL:

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VHL Gene

protein-coding GIFtS: 71

Aliases &
Descriptions
for VHL

Summaries
for VHL

Genomic Location
for VHL

Proteins
for VHL

Protein Domains/
Families
for VHL

Gene Function
for VHL

Pathways & Interactions
for VHL

Drugs & Compounds
for VHL

Transcripts
for VHL

Expression
for VHL

Orthologs
for VHL

Paralogs
for VHL

SNPs/Variants
for VHL

Disorders & Mutations
for VHL

Medical News
for VHL

Publications
for VHL

Search for VHL

Genome Databases showing VHL

Other Databases showing VHL

Specialized Databases showing VHL

Licensable Technologies
for VHL

Services
for VHL

Gene Index: 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

VHL Gene

protein-coding GIFtS: 71

Aliases & Descriptionsfor VHL

Summariesfor VHL

Genomic Locationfor VHL

Proteinsfor VHL

Protein Domains/Familiesfor VHL

Gene Functionfor VHL

Pathways & Interactionsfor VHL

Drugs & Compoundsfor VHL

Transcriptsfor VHL

Expression for VHL

Orthologsfor VHL

Paralogsfor VHL

SNPs/Variantsfor VHL

Disorders & Mutationsfor VHL

Medical Newsfor VHL

Publicationsfor VHL

Search for VHL

Genome Databases showing VHL

Other Databases showing VHL

Specialized Databases showing VHL

Licensable Technologiesfor VHL

Servicesfor VHL

Gene Index: 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

Aliases &
Descriptions
for VHL

Summaries
for VHL

Genomic Location
for VHL

Proteins
for VHL

Protein Domains/
Families
for VHL

Gene Function
for VHL

Pathways & Interactions
for VHL

Drugs & Compounds
for VHL

Transcripts
for VHL

Expression
for VHL

Orthologs
for VHL

Paralogs
for VHL

SNPs/Variants
for VHL

Disorders & Mutations
for VHL

Medical News
for VHL

Publications
for VHL

Licensable Technologies
for VHL

Services
for VHL