VHL

Gene Information

Official Symbol: VHL
Official Name: von Hippel-Lindau tumor suppressor
Aliases and Previous Symbols: N/A
Entrez ID: 7428
UniProt: P40337
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez 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. [provided by RefSeq, Jul 2008].
UniProt Summary: Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as a 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. Ubiquitinates, in an oxygen-responsive manner, ADRB2. {ECO:0000269|PubMed:10944113, ECO:0000269|PubMed:17981124, ECO:0000269|PubMed:19584355}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
LJH685 5μM R02 exp73	-2.25
ABT-702 5μM R06 exp261	-2.24
Arsenate 40μM R06 exp264	-2.2
Hydroxyurea 100μM R07 exp329	-2.01
proTAME 5μM R04 exp187	-1.88
BRD2 inhibitor II 20μM R07 exp341	-1.84
Wortmannin 5μM R00 exp38	-1.75
iCRT14 30μM R08 exp492	1.76
UM0129480 7μM R02 exp85	1.76
Olaparib 4μM R08 exp512	1.8
Doxorubicin 0.02μM R08 exp478	1.81
Staurosporine 0.02μM R08 exp524	1.89
PU-H71 1μM R08 exp515	1.98
Benzoate 20000μM R08 exp456	2.08
5-Fluorouracil 20μM R00 exp2	2.14
Artemisinin 50μM R08 exp450	2.26
6-Thio-2-deoxyguanosine 2μM R06 exp259	2.3
Bleomycin 5μM R08 exp459	2.6
Senexin-A 25μM R07 exp400	3.06
Etoposide 0.3μM R05 exp199	3.21

Gene	Correlation
RPTOR	0.64
DOHH	0.575
WDR24	0.569
MED16	0.556
THG1L	0.532
MTOR	0.53
BAK1	0.512
NSD1	0.51
BAP1	0.508
ENY2	0.502
CCDC101	0.498
FAF2	0.492
DR1	0.491
PELO	0.49
APAF1	0.487
RNMT	0.486
GMPPB	0.482
GFPT1	0.482
TLE4	0.48
MLLT1	0.477
EXOC4	0.47
GNB1L	0.47
ID3	0.468
TSEN54	0.467
RTCB	0.466
CBFB	0.462
UBE2G2	0.456
TTI2	0.455
NAE1	0.454
LAMTOR5	0.45
ADSL	0.449
UAP1	0.449
TRIM28	0.446
CASP9	0.441
MED23	0.44
LAMTOR4	0.439
DPAGT1	0.436
PLAA	0.435
SERF2	0.433
FH	0.429
ALG1	0.428
CSNK2B	0.427
WDR59	0.427
MLST8	0.426
MED4	0.421
VDAC2	0.421
ZNF592	0.421
MARCH5	0.42
SSBP2	0.419
PPP2R3C	0.416
SSB	0.415
PMM2	0.414
UBQLN1	0.414
TSEN34	0.414
DHPS	0.411
PAX5	0.41
HSPD1	0.409
RPP21	0.402
EGLN1	0.4

Global Fraction of Cell Lines Where Essential: 501/739

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	1/1
909776.0	1/1
bile duct	24/28
blood	16/28
bone	16/26
breast	19/33
central nervous system	41/56
cervix	3/4
colorectal	9/17
esophagus	12/13
fibroblast	1/1
gastric	8/16
kidney	4/21
liver	16/20
lung	55/75
lymphocyte	10/16
ovary	20/26
pancreas	17/24
peripheral nervous system	15/16
plasma cell	9/15
prostate	0/1
skin	22/24
soft tissue	4/9
thyroid	2/2
upper aerodigestive	18/22
urinary tract	21/29
uterus	2/5

Essentiality in NALM6

Essentiality Rank: 2119
Expression level (log2 read counts): 7.12

Expression Distribution

negative regulation of transcription from RNA polymerase II promoter in response to hypoxia
VCB complex
negative regulation of transcription from RNA polymerase II promoter in response to stress
negative regulation of receptor signaling pathway via JAK-STAT
negative regulation of receptor signaling pathway via STAT
regulation of transcription from RNA polymerase II promoter in response to hypoxia
regulation of transcription from RNA polymerase II promoter in response to stress
regulation of DNA-templated transcription in response to stress
regulation of receptor signaling pathway via JAK-STAT
regulation of receptor signaling pathway via STAT
protein stabilization
cellular response to hypoxia
cellular response to decreased oxygen levels
cellular response to oxygen levels
ubiquitin protein ligase activity
ubiquitin-protein transferase activity
regulation of protein stability
transcription factor binding
response to hypoxia
enzyme binding
response to decreased oxygen levels
post-translational protein modification
response to oxygen levels
negative regulation of cell population proliferation
protein ubiquitination
cell morphogenesis
protein modification by small protein conjugation
cellular component morphogenesis
negative regulation of transcription by RNA polymerase II
negative regulation of apoptotic process
negative regulation of programmed cell death
positive regulation of cell differentiation
protein modification by small protein conjugation or removal
negative regulation of cell death
endoplasmic reticulum
response to abiotic stimulus
negative regulation of transcription, DNA-templated
negative regulation of nucleic acid-templated transcription
negative regulation of RNA biosynthetic process
mitochondrion