CDK1
cyclin dependent kinase 1, the group of Cyclin dependent kinases
Basic information
Region (hg38): 10:60778330-60794852
Previous symbols: [ "CDC2" ]
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 CDK1 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 | 0 | 1 |
Variants in CDK1
This is a list of pathogenic ClinVar variants found in the CDK1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 10-60785677-C-G | not specified | Uncertain significance (Oct 26, 2021) | ||
| 10-60788210-A-G | not specified | Uncertain significance (Apr 12, 2022) | ||
| 10-60792042-C-T | Benign (Mar 29, 2018) | |||
| 10-60792237-G-A | not specified | Uncertain significance (Dec 22, 2023) | ||
| 10-60793917-A-G | not specified | Uncertain significance (Feb 17, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CDK1 | protein_coding | protein_coding | ENST00000395284 | 7 | 16522 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.992 | 0.00794 | 118842 | 0 | 1 | 118843 | 0.00000421 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.97 | 48 | 151 | 0.318 | 0.00000701 | 1948 |
| Missense in Polyphen | 6 | 58.495 | 0.10257 | 804 | ||
| Synonymous | 0.614 | 44 | 49.5 | 0.889 | 0.00000213 | 550 |
| Loss of Function | 3.52 | 0 | 14.5 | 0.00 | 7.03e-7 | 196 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000318 | 0.0000318 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition, and regulates G1 progress and G1-S transition via association with multiple interphase cyclins. Required in higher cells for entry into S-phase and mitosis. Phosphorylates PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl- xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, LMNA, LMNB, LMNC, LBR, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, UL40/R2, RAB4A, RAP1GAP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SAMHD1, SIRT2 and RUNX2. CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs. Essential for early stages of embryonic development. During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation. Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis. Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair. Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C- mediated dephosphorylation and restoring cell cycle progression. In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons. The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis. NEDD1 phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis. The phosphorylation of Bcl- xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis. In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration. CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis (PubMed:26549230). {ECO:0000269|PubMed:16371510, ECO:0000269|PubMed:16407259, ECO:0000269|PubMed:16933150, ECO:0000269|PubMed:17459720, ECO:0000269|PubMed:18356527, ECO:0000269|PubMed:18480403, ECO:0000269|PubMed:19509060, ECO:0000269|PubMed:19917720, ECO:0000269|PubMed:20171170, ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:20937773, ECO:0000269|PubMed:21063390, ECO:0000269|PubMed:23601106, ECO:0000269|PubMed:23602554, ECO:0000269|PubMed:25556658, ECO:0000269|PubMed:26549230}.;
- Pathway
- Cell cycle - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);p53 signaling pathway - Homo sapiens (human);Gap junction - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Busulfan Pathway, Pharmacodynamics;Herpes simplex infection - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);Cell Cycle;miRNA Regulation of DNA Damage Response;Mitotic G1-G1-S phases;Regulation of Microtubule Cytoskeleton;Spinal Cord Injury;Retinoblastoma (RB) in Cancer;ATM Signaling Pathway;PPAR Alpha Pathway;Nuclear Receptors Meta-Pathway;TGF-beta Signaling Pathway;ATM Signaling Network in Development and Disease;G1 to S cell cycle control;DNA Damage Response;Transcriptional regulation by RUNX2;Signal Transduction;Gene expression (Transcription);sonic hedgehog receptor ptc1 regulates cell cycle;regulation of splicing through sam68;estrogen responsive protein efp controls cell cycle and breast tumors growth;stathmin and breast cancer resistance to antimicrotubule agents;cdc25 and chk1 regulatory pathway in response to dna damage;cell cycle: g1/s check point;cyclins and cell cycle regulation;how progesterone initiates the oocyte maturation;protein kinase a at the centrosome;regulation of cell cycle progression by plk3;Generic Transcription Pathway;MAPK6/MAPK4 signaling;Post-translational protein modification;Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex;Metabolism of proteins;MASTL Facilitates Mitotic Progression;RNA Polymerase II Transcription;G2/M DNA damage checkpoint;G2/M DNA replication checkpoint;G2/M Checkpoints;TCR;Cell Cycle Checkpoints;Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1;G0 and Early G1;p73 transcription factor network;Activation of E2F1 target genes at G1/S;G1/S-Specific Transcription;E2F mediated regulation of DNA replication;Mitotic G1-G1/S phases;akap95 role in mitosis and chromosome dynamics;cell cycle: g2/m checkpoint;Phosphorylation of proteins involved in the G2/M transition by Cyclin A:Cdc2 complexes;Cyclin A/B1/B2 associated events during G2/M transition;RAF-independent MAPK1/3 activation;IL-7 signaling;Nuclear Pore Complex (NPC) Disassembly;TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest;TGF_beta_Receptor;Regulation of PLK1 Activity at G2/M Transition;TP53 Regulates Transcription of Cell Cycle Genes;Golgi Cisternae Pericentriolar Stack Reorganization;EGFR1;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;The role of GTSE1 in G2/M progression after G2 checkpoint;AURKA Activation by TPX2;rb tumor suppressor/checkpoint signaling in response to dna damage;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Regulation of TP53 Degradation;Regulation of TP53 Expression and Degradation;G2/M Transition;Mitotic G2-G2/M phases;JAK STAT pathway and regulation;Ovarian tumor domain proteases;Condensation of Prophase Chromosomes;Activation of NIMA Kinases NEK9, NEK6, NEK7;Deubiquitination;G1/S Transition;EPO signaling;E2F-enabled inhibition of pre-replication complex formation;Depolymerisation of the Nuclear Lamina;Nuclear Envelope Breakdown;Mitotic Prophase;Condensation of Prometaphase Chromosomes;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;Phosphorylation of Emi1;Regulation of APC/C activators between G1/S and early anaphase;Phosphorylation of the APC/C;Cdc20:Phospho-APC/C mediated degradation of Cyclin A;APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint;APC/C:Cdc20 mediated degradation of Cyclin B;APC/C:Cdc20 mediated degradation of mitotic proteins;Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins;APC/C-mediated degradation of cell cycle proteins;Regulation of mitotic cell cycle;Cell Cycle;Resolution of Sister Chromatid Cohesion;MAPK3 (ERK1) activation;VEGF;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Retinoic acid receptors-mediated signaling;AP-1 transcription factor network;PLK1 signaling events;FOXM1 transcription factor network;E2F transcription factor network;Cilium Assembly;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.822
Intolerance Scores
- loftool
- rvis_EVS
- -0.1
- rvis_percentile_EVS
- 46.2
Haploinsufficiency Scores
- pHI
- 1.00
- hipred
- Y
- hipred_score
- 0.728
- ghis
- 0.744
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.781
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Low | Medium |
Mouse Genome Informatics
- Gene name
- Cdk1
- Phenotype
- endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; vision/eye phenotype; reproductive system phenotype; normal 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); neoplasm; embryo phenotype; liver/biliary system phenotype;
Zebrafish Information Network
- Gene name
- cdk1
- Affected structure
- trunk
- Phenotype tag
- abnormal
- Phenotype quality
- curved dorsal
Gene ontology
- Biological process
- G2/M transition of mitotic cell cycle;activation of MAPK activity;microtubule cytoskeleton organization;DNA replication;DNA repair;protein phosphorylation;apoptotic process;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;mitotic nuclear envelope disassembly;mitotic G2 DNA damage checkpoint;centrosome cycle;pronuclear fusion;cell aging;cell population proliferation;regulation of G2/M transition of mitotic cell cycle;positive regulation of gene expression;positive regulation of G2/M transition of mitotic cell cycle;regulation of Schwann cell differentiation;response to organic cyclic compound;response to amine;response to activity;cell migration;histone phosphorylation;protein deubiquitination;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;chromosome condensation;epithelial cell differentiation;animal organ regeneration;anaphase-promoting complex-dependent catabolic process;obsolete positive regulation of protein import into nucleus, translocation;protein localization to kinetochore;negative regulation of apoptotic process;mitotic cell cycle phase transition;response to ethanol;positive regulation of DNA replication;regulation of embryonic development;response to cadmium ion;response to copper ion;viral entry into host cell;response to axon injury;cell division;ventricular cardiac muscle cell development;positive regulation of cardiac muscle cell proliferation;protein-containing complex assembly;cellular response to hydrogen peroxide;Golgi disassembly;ciliary basal body-plasma membrane docking;positive regulation of protein localization to nucleus;positive regulation of mitochondrial ATP synthesis coupled electron transport
- Cellular component
- cyclin-dependent protein kinase holoenzyme complex;nuclear chromosome, telomeric region;nucleus;nucleoplasm;cytoplasm;mitochondrion;mitochondrial matrix;endoplasmic reticulum membrane;centrosome;cytosol;spindle microtubule;membrane;midbody;extracellular exosome;mitotic spindle;cyclin B1-CDK1 complex
- Molecular function
- virus receptor activity;chromatin binding;protein kinase activity;protein serine/threonine kinase activity;cyclin-dependent protein serine/threonine kinase activity;protein binding;ATP binding;RNA polymerase II CTD heptapeptide repeat kinase activity;cyclin binding;Hsp70 protein binding;histone kinase activity;cyclin-dependent protein kinase activity