CDK12

cyclin dependent kinase 12, the group of Cyclin dependent kinases

Basic information

Region (hg38): 17:39461485-39564907

Previous symbols: [ "CRKRS" ]

Links

ENSG00000167258 ∙ NCBI:51755 ∙ OMIM:615514 ∙ HGNC:24224 ∙ Uniprot:Q9NYV4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Tourette syndrome (No Known Disease Relationship), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CDK12 gene.

• Inborn genetic diseases (36 variants)
• Hereditary breast ovarian cancer syndrome (31 variants)
• not provided (20 variants)
• not specified (18 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDK12 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	3	8
missense			35	7	1	43
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				13	17	30
Total	0	0	36	25	21

Variants in CDK12

This is a list of pathogenic ClinVar variants found in the CDK12 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-39461967-C-T			Benign (Jun 14, 2019)
17-39462045-T-C		Hereditary breast ovarian cancer syndrome	Likely benign (Apr 19, 2022)
17-39462052-T-C		Hereditary breast ovarian cancer syndrome	Likely benign (Apr 19, 2022)
17-39462082-C-T		not specified	Uncertain significance (Jul 19, 2022)
17-39462305-T-A		CDK12-related disorder	Benign (Aug 05, 2019)
17-39462331-T-C		not specified	Uncertain significance (Jan 23, 2023)
17-39462338-C-T		CDK12-related disorder	Likely benign (Apr 29, 2019)
17-39462342-C-T		Hereditary breast ovarian cancer syndrome • CDK12-related disorder	Benign/Likely benign (Apr 19, 2022)
17-39462420-A-G		not specified	Uncertain significance (Oct 17, 2023)
17-39462441-A-G		not specified	Uncertain significance (Sep 07, 2022)
17-39462455-C-T		CDK12-related disorder	Likely benign (Jun 30, 2019)
17-39462495-T-A		not specified	Uncertain significance (Jul 07, 2022)
17-39462615-G-A		not specified	Uncertain significance (Apr 07, 2022)
17-39462684-G-C		not specified	Uncertain significance (Mar 06, 2023)
17-39462703-A-C		not specified	Uncertain significance (Mar 01, 2024)
17-39462730-C-G		not specified	Uncertain significance (Apr 20, 2023)
17-39462742-A-C		not specified	Uncertain significance (Jan 04, 2024)
17-39462763-C-A		not specified	Uncertain significance (Nov 17, 2022)
17-39462785-G-A		Hereditary breast ovarian cancer syndrome • CDK12-related disorder	Benign (Apr 19, 2022)
17-39462829-C-G		not specified	Uncertain significance (Apr 26, 2023)
17-39462878-C-T		Hereditary breast ovarian cancer syndrome	Likely benign (Apr 19, 2022)
17-39462930-T-C		not specified	Uncertain significance (Aug 22, 2023)
17-39462983-C-G		CDK12-related disorder	Likely benign (Aug 05, 2019)
17-39463037-A-G		Hereditary breast ovarian cancer syndrome • CDK12-related disorder	Likely benign (Apr 19, 2022)
17-39470710-G-A			Benign (Jun 14, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDK12	protein_coding	protein_coding	ENST00000447079	14	103397

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.42e-8	125743	0	4	125747	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.52	596	797	0.748	0.0000403	9639
Missense in Polyphen		128	280.02	0.4571		3432
Synonymous	0.430	296	306	0.969	0.0000153	3065
Loss of Function	6.92	3	61.7	0.0486	0.00000357	728

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000181	0.0000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:11683387, ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}.
• Disease: DISEASE: Note=Chromosomal aberrations involving CDK12 may be a cause gastric cancer. Deletions within 17q12 region producing fusion transcripts with ERBB2, leading to CDK12-ERBB2 fusion leading to trunctated CDK12 protein not in-frame with ERBB2.
• Pathway: Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;TP53 Regulates Transcription of DNA Repair Genes;Transcriptional Regulation by TP53 (Consensus)

Recessive Scores

• pRec: 0.161

Intolerance Scores

• loftool: 0.134
• rvis_EVS: -1.17
• rvis_percentile_EVS: 6.06

Haploinsufficiency Scores

• pHI: 0.588
• hipred: Y
• hipred_score: 0.796
• ghis: 0.622

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.948

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cdk12
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; cellular phenotype

Gene ontology

• Biological process: transcription elongation from RNA polymerase II promoter;mRNA processing;protein phosphorylation;RNA splicing;positive regulation of transcription elongation from RNA polymerase II promoter;regulation of MAP kinase activity;regulation of RNA splicing;positive regulation of transcription by RNA polymerase II;protein autophosphorylation;regulation of cell cycle;phosphorylation of RNA polymerase II C-terminal domain;negative regulation of stem cell differentiation
• Cellular component: cyclin-dependent protein kinase holoenzyme complex;nuclear chromatin;fibrillar center;cyclin K-CDK12 complex;nucleus;nucleoplasm;chromosome;cyclin/CDK positive transcription elongation factor complex;nuclear speck;nuclear cyclin-dependent protein kinase holoenzyme complex
• Molecular function: protein kinase activity;cyclin-dependent protein serine/threonine kinase activity;protein binding;ATP binding;transcription factor binding;RNA polymerase II CTD heptapeptide repeat kinase activity;protein kinase binding;cyclin binding;transcription regulatory region DNA binding