CDK12
Basic information
Region (hg38): 17:39461486-39567559
Previous symbols: [ "CRKRS" ]
Links
Phenotypes
GenCC
Source:
- Tourette syndrome (No Known Disease Relationship), mode of inheritance: Unknown
ClinVar
This is a list of variants' phenotypes submitted to
- 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.
Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 518 | 520 | ||||
missense | 842 | 20 | 863 | |||
nonsense | 3 | |||||
start loss | 0 | |||||
frameshift | 2 | |||||
splice donor/acceptor (+/-2bp) | 1 | |||||
Total | 0 | 1 | 848 | 538 | 2 |
GnomAD
Source:
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:
- 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