CDK2
cyclin dependent kinase 2, the group of Cyclin dependent kinases
Basic information
Region (hg38): 12:55966780-55972789
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (2 variants)
- not provided (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDK2 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 | 1 | |||||
| missense | 2 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 2 | 1 | 0 |
Variants in CDK2
This is a list of pathogenic ClinVar variants found in the CDK2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 12-55967036-A-C | not specified | Uncertain significance (Dec 28, 2023) | ||
| 12-55967910-A-C | not specified | Uncertain significance (Dec 19, 2022) | ||
| 12-55968090-T-G | not specified | Uncertain significance (Nov 17, 2022) | ||
| 12-55971553-T-A | Likely benign (Apr 27, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CDK2 | protein_coding | protein_coding | ENST00000266970 | 7 | 6016 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.611 | 0.389 | 125744 | 0 | 3 | 125747 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.49 | 75 | 165 | 0.454 | 0.00000901 | 1925 |
| Missense in Polyphen | 18 | 74.541 | 0.24148 | 887 | ||
| Synonymous | 0.0970 | 61 | 62.0 | 0.984 | 0.00000290 | 620 |
| Loss of Function | 3.01 | 3 | 16.0 | 0.188 | 9.42e-7 | 167 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000290 | 0.0000290 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000879 | 0.00000879 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2- mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization. Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity). Phosphorylates CDK2AP2 (PubMed:12944431). {ECO:0000250|UniProtKB:P97377, ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:10884347, ECO:0000269|PubMed:10995386, ECO:0000269|PubMed:10995387, ECO:0000269|PubMed:11051553, ECO:0000269|PubMed:11113184, ECO:0000269|PubMed:12944431, ECO:0000269|PubMed:15800615, ECO:0000269|PubMed:17495531, ECO:0000269|PubMed:18372919, ECO:0000269|PubMed:19966300, ECO:0000269|PubMed:20079829, ECO:0000269|PubMed:20147522, ECO:0000269|PubMed:20195506, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:21319273, ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:28666995}.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Cell cycle - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);p53 signaling pathway - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);Cell Cycle;miRNA Regulation of DNA Damage Response;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Signaling Pathways in Glioblastoma;Oncostatin M Signaling Pathway;Spinal Cord Injury;Retinoblastoma (RB) in Cancer;Aryl Hydrocarbon Receptor;Vitamin D Receptor Pathway;regulation of p27 phosphorylation during cell cycle progression;PI3K-Akt Signaling Pathway;G1 to S cell cycle control;DNA Replication;ID signaling pathway;DNA Damage Response;Signaling by PTK6;RAGE;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Signal Transduction;Gene expression (Transcription);DNA Double-Strand Break Repair;cyclin e destruction pathway;influence of ras and rho proteins on g1 to s transition;estrogen responsive protein efp controls cell cycle and breast tumors growth;cell cycle: g1/s check point;cyclins and cell cycle regulation;e2f1 destruction pathway;cdk regulation of dna replication;Generic Transcription Pathway;DNA Damage/Telomere Stress Induced Senescence;Senescence-Associated Secretory Phenotype (SASP);Cellular Senescence;Homology Directed Repair;Factors involved in megakaryocyte development and platelet production;Cellular responses to stress;RNA Polymerase II Transcription;p53-Dependent G1 DNA Damage Response;p53-Dependent G1/S DNA damage checkpoint;G1/S DNA Damage Checkpoints;Activation of ATR in response to replication stress;G2/M Checkpoints;Cell Cycle Checkpoints;G0 and Early G1;SCF(Skp2)-mediated degradation of p27/p21;p73 transcription factor network;Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes;Cyclin E associated events during G1/S transition ;KitReceptor;PTK6 Regulates Cell Cycle;Activation of the pre-replicative complex;Mitotic G1-G1/S phases;Cyclin A:Cdk2-associated events at S phase entry;Orc1 removal from chromatin;BCR;DNA Replication;Switching of origins to a post-replicative state;Synthesis of DNA;S Phase;G2 Phase;Cyclin A/B1/B2 associated events during G2/M transition;Cellular responses to external stimuli;IL-7 signaling;TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest;p53 signaling pathway;TGF_beta_Receptor;TP53 Regulates Transcription of Cell Cycle Genes;EGFR1;Hemostasis;rb tumor suppressor/checkpoint signaling in response to dna damage;Regulation of TP53 Degradation;Regulation of TP53 Expression and Degradation;G2/M Transition;Mitotic G2-G2/M phases;JAK STAT pathway and regulation;IL2;Signaling by Non-Receptor Tyrosine Kinases;G1/S Transition;EPO signaling;Regulation of TP53 Activity through Phosphorylation;IL2-mediated signaling events;Regulation of TP53 Activity;Transcriptional Regulation by TP53;DNA Replication Pre-Initiation;M/G1 Transition;Regulation of APC/C activators between G1/S and early anaphase;CDK-mediated phosphorylation and removal of Cdc6;APC/C-mediated degradation of cell cycle proteins;Regulation of mitotic cell cycle;Cell Cycle;VEGF;ID;Cell Cycle, Mitotic;mTOR signaling pathway;BARD1 signaling events;Processing of DNA double-strand break ends;FOXM1 transcription factor network;FoxO family signaling;Regulation of retinoblastoma protein;ATR signaling pathway;Regulation of nuclear SMAD2/3 signaling;E2F transcription factor network;p53 pathway;Signaling events mediated by PRL
(Consensus)
Recessive Scores
- pRec
- 0.865
Intolerance Scores
- loftool
- 0.251
- rvis_EVS
- -0.16
- rvis_percentile_EVS
- 41.25
Haploinsufficiency Scores
- pHI
- 1.00
- hipred
- Y
- hipred_score
- 0.802
- ghis
- 0.695
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.976
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cdk2
- Phenotype
- liver/biliary system phenotype; embryo phenotype; neoplasm; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); reproductive system phenotype; vision/eye phenotype; immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); muscle phenotype;
Gene ontology
- Biological process
- G1/S transition of mitotic cell cycle;G2/M transition of mitotic cell cycle;negative regulation of transcription by RNA polymerase II;DNA replication;DNA repair;protein phosphorylation;potassium ion transport;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;centriole replication;Ras protein signal transduction;positive regulation of cell population proliferation;regulation of G2/M transition of mitotic cell cycle;histone phosphorylation;peptidyl-serine phosphorylation;anaphase-promoting complex-dependent catabolic process;mitotic G1 DNA damage checkpoint;positive regulation of DNA-dependent DNA replication initiation;positive regulation of transcription, DNA-templated;centrosome duplication;cell division;meiotic cell cycle;regulation of gene silencing;cellular response to nitric oxide;regulation of signal transduction by p53 class mediator
- Cellular component
- cyclin-dependent protein kinase holoenzyme complex;chromosome, telomeric region;condensed chromosome;X chromosome;Y chromosome;nucleus;nucleoplasm;transcription factor complex;cytoplasm;endosome;centrosome;cytosol;Cajal body;cyclin A1-CDK2 complex;cyclin A2-CDK2 complex;cyclin E1-CDK2 complex;cyclin E2-CDK2 complex
- Molecular function
- magnesium ion binding;protein serine/threonine kinase activity;cyclin-dependent protein serine/threonine kinase activity;protein binding;ATP binding;protein domain specific binding;cyclin binding;histone kinase activity;cyclin-dependent protein kinase activity