TISIDB

Summary
Symbol	CDK12
Name	cyclin-dependent kinase 12
Aliases	CRK7; CRKR; KIAA0904; CDC2 related protein kinase 7; CRKRS; Cdc2-related kinase, arginine/serine-rich; CDC2- ......
Chromosomal Location	17q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Nucleus. Nucleus speckle. Note=Colocalized with nuclear speckles throughout interphase.
Domain	PF00069 Protein kinase domain
Function	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.

> Gene Ontology [ TOP ]
Biological Process	GO:0006397 mRNA processing GO:0008380 RNA splicing GO:0043405 regulation of MAP kinase activity GO:0043484 regulation of RNA splicing GO:0046777 protein autophosphorylation GO:0070816 phosphorylation of RNA polymerase II C-terminal domain GO:0071900 regulation of protein serine/threonine kinase activity
Molecular Function	GO:0004674 protein serine/threonine kinase activity GO:0004693 cyclin-dependent protein serine/threonine kinase activity GO:0008353 RNA polymerase II carboxy-terminal domain kinase activity GO:0030332 cyclin binding GO:0097472 cyclin-dependent protein kinase activity
Cellular Component	GO:0000307 cyclin-dependent protein kinase holoenzyme complex GO:0002944 cyclin K-CDK12 complex GO:0016604 nuclear body GO:0016607 nuclear speck GO:0019908 nuclear cyclin-dependent protein kinase holoenzyme complex GO:0061695 transferase complex, transferring phosphorus-containing groups GO:1902554 serine/threonine protein kinase complex GO:1902911 protein kinase complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-6796648: TP53 Regulates Transcription of DNA Repair Genes R-HSA-3700989: Transcriptional Regulation by TP53

Summary
Symbol	CDK12
Name	cyclin-dependent kinase 12
Aliases	CRK7; CRKR; KIAA0904; CDC2 related protein kinase 7; CRKRS; Cdc2-related kinase, arginine/serine-rich; CDC2- ......
Chromosomal Location	17q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CDK12 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	CDK12
Name	cyclin-dependent kinase 12
Aliases	CRK7; CRKR; KIAA0904; CDC2 related protein kinase 7; CRKRS; Cdc2-related kinase, arginine/serine-rich; CDC2- ......
Chromosomal Location	17q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

[ TOP ]

Statistical results of CDK12 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	logFC: 1.02; FDR: 0.007470	Sensitive to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	STARS Score: 4.28; FDR: 0.015	Resistant to T cell-mediated killing
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	CDK12
Name	cyclin-dependent kinase 12
Aliases	CRK7; CRKR; KIAA0904; CDC2 related protein kinase 7; CRKRS; Cdc2-related kinase, arginine/serine-rich; CDC2- ......
Chromosomal Location	17q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of CDK12 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.206	0.385
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.516	0.708
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.023	0.982
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.068	0.772
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.13	0.96
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.01	0.998
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.243	0.511
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.203	0.905
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.265	0.891
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.112	0.923
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.954	0.544
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.019	0.787

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CDK12 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	14.8	1.4	13.4	0.0181
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	14.8	1.7	13.1	0.032
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	14.3	0	14.3	0.238
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	25	0	25	0.473
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	0	5.3	0.507
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	CDK12
Name	cyclin-dependent kinase 12
Aliases	CRK7; CRKR; KIAA0904; CDC2 related protein kinase 7; CRKRS; Cdc2-related kinase, arginine/serine-rich; CDC2- ......
Chromosomal Location	17q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CDK12. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	CDK12
Name	cyclin-dependent kinase 12
Aliases	CRK7; CRKR; KIAA0904; CDC2 related protein kinase 7; CRKRS; Cdc2-related kinase, arginine/serine-rich; CDC2- ......
Chromosomal Location	17q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CDK12. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CDK12. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CDK12
Name	cyclin-dependent kinase 12
Aliases	CRK7; CRKR; KIAA0904; CDC2 related protein kinase 7; CRKRS; Cdc2-related kinase, arginine/serine-rich; CDC2- ......
Chromosomal Location	17q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CDK12. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	CDK12
Name	cyclin-dependent kinase 12
Aliases	CRK7; CRKR; KIAA0904; CDC2 related protein kinase 7; CRKRS; Cdc2-related kinase, arginine/serine-rich; CDC2- ......
Chromosomal Location	17q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CDK12 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CDK12
Name	cyclin-dependent kinase 12
Aliases	CRK7; CRKR; KIAA0904; CDC2 related protein kinase 7; CRKRS; Cdc2-related kinase, arginine/serine-rich; CDC2- ......
Chromosomal Location	17q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CDK12 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CDK12
Name	cyclin-dependent kinase 12
Aliases	CRK7; CRKR; KIAA0904; CDC2 related protein kinase 7; CRKRS; Cdc2-related kinase, arginine/serine-rich; CDC2- ......
Chromosomal Location	17q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CDK12 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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