======= VHL =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: VHL
  * **<color #00a2e8>Official Name</color>**: von Hippel-Lindau tumor suppressor
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=7428|7428]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P40337|P40337]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=VHL&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20VHL|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/608537|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|VHL|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|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|
|negative regulation of signal transduction|
|proteolysis|
|negative regulation of RNA metabolic process|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|negative regulation of cellular macromolecule biosynthetic process|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|negative regulation of cellular biosynthetic process|
|positive regulation of transcription, DNA-templated|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|regulation of programmed cell death|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|regulation of cell death|
|cellular response to stress|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|regulation of cell differentiation|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|membrane|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

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

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:r:rptor|RPTOR]]|0.64|
|[[:human genes:d:dohh|DOHH]]|0.575|
|[[:human genes:w:wdr24|WDR24]]|0.569|
|[[:human genes:m:med16|MED16]]|0.556|
|[[:human genes:t:thg1l|THG1L]]|0.532|
|[[:human genes:m:mtor|MTOR]]|0.53|
|[[:human genes:b:bak1|BAK1]]|0.512|
|[[:human genes:n:nsd1|NSD1]]|0.51|
|[[:human genes:b:bap1|BAP1]]|0.508|
|[[:human genes:e:eny2|ENY2]]|0.502|
|[[:human genes:c:ccdc101|CCDC101]]|0.498|
|[[:human genes:f:faf2|FAF2]]|0.492|
|[[:human genes:d:dr1|DR1]]|0.491|
|[[:human genes:p:pelo|PELO]]|0.49|
|[[:human genes:a:apaf1|APAF1]]|0.487|
|[[:human genes:r:rnmt|RNMT]]|0.486|
|[[:human genes:g:gmppb|GMPPB]]|0.482|
|[[:human genes:g:gfpt1|GFPT1]]|0.482|
|[[:human genes:t:tle4|TLE4]]|0.48|
|[[:human genes:m:mllt1|MLLT1]]|0.477|
|[[:human genes:e:exoc4|EXOC4]]|0.47|
|[[:human genes:g:gnb1l|GNB1L]]|0.47|
|[[:human genes:i:id3|ID3]]|0.468|
|[[:human genes:t:tsen54|TSEN54]]|0.467|
|[[:human genes:r:rtcb|RTCB]]|0.466|
|[[:human genes:c:cbfb|CBFB]]|0.462|
|[[:human genes:u:ube2g2|UBE2G2]]|0.456|
|[[:human genes:t:tti2|TTI2]]|0.455|
|[[:human genes:n:nae1|NAE1]]|0.454|
|[[:human genes:l:lamtor5|LAMTOR5]]|0.45|
|[[:human genes:a:adsl|ADSL]]|0.449|
|[[:human genes:u:uap1|UAP1]]|0.449|
|[[:human genes:t:trim28|TRIM28]]|0.446|
|[[:human genes:c:casp9|CASP9]]|0.441|
|[[:human genes:m:med23|MED23]]|0.44|
|[[:human genes:l:lamtor4|LAMTOR4]]|0.439|
|[[:human genes:d:dpagt1|DPAGT1]]|0.436|
|[[:human genes:p:plaa|PLAA]]|0.435|
|[[:human genes:s:serf2|SERF2]]|0.433|
|[[:human genes:f:fh|FH]]|0.429|
|[[:human genes:a:alg1|ALG1]]|0.428|
|[[:human genes:c:csnk2b|CSNK2B]]|0.427|
|[[:human genes:w:wdr59|WDR59]]|0.427|
|[[:human genes:m:mlst8|MLST8]]|0.426|
|[[:human genes:m:med4|MED4]]|0.421|
|[[:human genes:v:vdac2|VDAC2]]|0.421|
|[[:human genes:z:znf592|ZNF592]]|0.421|
|[[:human genes:m:march5|MARCH5]]|0.42|
|[[:human genes:s:ssbp2|SSBP2]]|0.419|
|[[:human genes:p:ppp2r3c|PPP2R3C]]|0.416|
|[[:human genes:s:ssb|SSB]]|0.415|
|[[:human genes:p:pmm2|PMM2]]|0.414|
|[[:human genes:u:ubqln1|UBQLN1]]|0.414|
|[[:human genes:t:tsen34|TSEN34]]|0.414|
|[[:human genes:d:dhps|DHPS]]|0.411|
|[[:human genes:p:pax5|PAX5]]|0.41|
|[[:human genes:h:hspd1|HSPD1]]|0.409|
|[[:human genes:r:rpp21|RPP21]]|0.402|
|[[:human genes:e:egln1|EGLN1]]|0.4|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
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|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 2119
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.12 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='VHL Expression in NALM6 Cells: 7.12'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>