CDK12 [The Human Chemical-Genetic Interaction Map Project]

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======= CDK12 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: CDK12
  * **<color #00a2e8>Official Name</color>**: cyclin dependent kinase 12
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=51755|51755]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q9NYV4|Q9NYV4]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=CDK12&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20CDK12|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/615514|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  Cyclin-dependent kinase that phosphorylates the C- terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors. {ECO:0000269|PubMed:11683387, ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}.

<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'>
|Pkinase|
|Pkinase Tyr|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|cyclin K-CDK12 complex|
|nuclear cyclin-dependent protein kinase holoenzyme complex|
|phosphorylation of RNA polymerase II C-terminal domain|
|cyclin/CDK positive transcription elongation factor complex|
|positive regulation of transcription elongation from RNA polymerase II promoter|
|RNA polymerase II CTD heptapeptide repeat kinase activity|
|negative regulation of stem cell differentiation|
|cyclin-dependent protein serine/threonine kinase activity|
|cyclin binding|
|regulation of transcription elongation from RNA polymerase II promoter|
|cyclin-dependent protein kinase holoenzyme complex|
|positive regulation of DNA-templated transcription, elongation|
|regulation of DNA-templated transcription, elongation|
|transcription elongation from RNA polymerase II promoter|
|DNA-templated transcription, elongation|
|regulation of stem cell differentiation|
|chromosome|
|fibrillar center|
|regulation of RNA splicing|
|protein autophosphorylation|
|transcription regulatory region DNA binding|
|nuclear chromatin|
|protein kinase activity|
|transcription factor binding|
|regulation of MAP kinase activity|
|RNA splicing|
|nuclear speck|
|protein kinase binding|
|mRNA processing|
|transcription by RNA polymerase II|
|regulation of protein serine/threonine kinase activity|
|transcription, DNA-templated|
|nucleic acid-templated transcription|
|RNA biosynthetic process|
|mRNA metabolic process|
|negative regulation of cell differentiation|
|regulation of MAPK cascade|
|regulation of protein kinase activity|
|regulation of kinase activity|
|RNA processing|
|negative regulation of developmental process|
|protein phosphorylation|
|regulation of transferase activity|
|nucleobase-containing compound biosynthetic process|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|regulation of cell cycle|
|positive regulation of transcription by RNA polymerase II|
|phosphorylation|
|organic cyclic compound biosynthetic process|
|regulation of protein phosphorylation|
|ATP binding|
|positive regulation of transcription, DNA-templated|
|regulation of phosphorylation|
|cellular nitrogen compound biosynthetic process|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|RNA metabolic process|
|cellular macromolecule biosynthetic process|
|positive regulation of RNA metabolic process|
|macromolecule biosynthetic process|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|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|
|gene expression|
|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:exp335|Aminopterin 0.005μM R07 exp335]]|-2.61|
|[[:results:exp444|THZ531 0.225μM R08 exp444]]|-2.58|
|[[:results:exp501|Methotrexate 0.01μM R08 exp501]]|-2.55|
|[[:results:exp450|Artemisinin 50μM R08 exp450]]|-2.21|
|[[:results:exp19|Etoposide 1μM R00 exp19]]|-1.99|
|[[:results:exp256|HMS-I1 10μM R06 exp256]]|-1.98|
|[[:results:exp24|Nocodazole 0.2μM R00 exp24]]|-1.96|
|[[:results:exp93|DABN racemic mixture R03 exp93]]|-1.92|
|[[:results:exp343|Centrinone 0.5μM R07 exp343]]|-1.9|
|[[:results:exp357|Dorsomorphin 5μM R07 exp357]]|-1.9|
|[[:results:exp85|UM0129480 7μM R02 exp85]]|-1.88|
|[[:results:exp417|Tubastatin-A 2.5μM R07 exp417]]|-1.84|
|[[:results:exp106|UM131593 0.2μM R03 exp106]]|-1.77|
|[[:results:exp21|MLN-4924 0.2μM R00 exp21]]|-1.73|
|[[:results:exp535|Trimetrexate 0.03μM R08 exp535]]|-1.7|
|[[:results:exp35|TRAIL 5ng/ml R00 exp35]]|1.71|
|[[:results:exp530|Thioridazine 5μM R08 exp530]]|1.84|
|[[:results:exp144|PFI-3 10μM R03 exp144]]|2.26|
|[[:results:exp101|Nicotinamide 1000μM R03 exp101]]|2.61|
|[[:results:exp120|Dimethyl-Sulfoxide 1pc R03 exp120]]|2.66|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:z:zfand5|ZFAND5]]|0.502|
|[[:human genes:s:smg7|SMG7]]|0.482|
|[[:human genes:a:akirin2|AKIRIN2]]|0.426|
|[[:human genes:s:setd1a|SETD1A]]|0.41|
|[[:human genes:c:ccnk|CCNK]]|0.409|
|[[:human genes:n:nupl1|NUPL1]]|0.403|
|[[:human genes:n:nup85|NUP85]]|0.4|
|[[:human genes:o:orc1|ORC1]]|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: 9/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|1/28|
|bone|0/25|
|breast|1/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|1/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|1/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|1/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|1/29|
|uterus|1/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 1319
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.43 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='CDK12 Expression in NALM6 Cells: 7.43'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>