CDK12

cyclin dependent kinase 12, the group of Cyclin dependent kinases

Basic information

Region (hg38): 17:39461486-39567559

Previous symbols: [ "CRKRS" ]

Links

ENSG00000167258NCBI:51755OMIM:615514HGNC:24224Uniprot:Q9NYV4AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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.

  • not_specified (1375 variants)
  • Hereditary_breast_ovarian_cancer_syndrome (27 variants)
  • CDK12-related_disorder (22 variants)
  • not_provided (15 variants)
  • Lung_adenocarcinoma (1 variants)
  • Hereditary_cancer (1 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. These statistics are base on transcript: NM_000016507.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
518
clinvar
2
clinvar
520
missense
1
clinvar
842
clinvar
20
clinvar
863
nonsense
3
clinvar
3
start loss
0
frameshift
2
clinvar
2
splice donor/acceptor (+/-2bp)
1
clinvar
1
Total 0 1 848 538 2
Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
CDK12protein_codingprotein_codingENST00000447079 14103397
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.002.42e-8125743041257470.0000159
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.525967970.7480.00004039639
Missense in Polyphen128280.020.45713432
Synonymous0.4302963060.9690.00001533065
Loss of Function6.92361.70.04860.00000357728

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.00005440.0000544
Finnish0.000.00
European (Non-Finnish)0.00001810.0000176
Middle Eastern0.00005440.0000544
South Asian0.000.00
Other0.0001630.000163

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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