GeneBe

CDK1

protein-coding

cyclin dependent kinase 1, the group of Cyclin dependent kinases

Gene summary

The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is a catalytic subunit of the highly conserved protein kinase complex known as M-phase promoting factor (MPF), which is essential for G2/M phase transitions of eukaryotic cell cycle. Mitotic cyclins stably associate with this protein and function as regulatory subunits. The kinase activity of this protein is controlled by cyclin accumulation and destruction through the cell cycle. The phosphorylation and dephosphorylation of this protein also play important regulatory roles in cell cycle control. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2023]

Previous symbols:
  • CDC2

MANE transcript

NM_001786.5

Inheritance

—

ClinVar variants

U:13B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr10:60,778,331-60,794,852

External References & Databases

Ensembl (ENSG00000170312)NCBI Gene (983)OMIM (116940)HGNC:1722GenCCUniProt (P06493)AlphaFoldClinVar (CDK1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~16.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CDK1 variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 10
not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001786.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
clinvar
 2
missense
10
clinvar
 10
nonsense
1
clinvar
 1
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total00130114
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 54 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001786.5RefSeqNP_001777.17MANE Select
ENST00000395284.8EnsemblENSP00000378699.37MANE Select
NM_001170406.1RefSeqNP_001163877.13Standard
NM_001170407.2RefSeqNP_001163878.13Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
cdk1Danio rerio

Structure: trunk

Quality: curved dorsal

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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)

Biological Process

  • G2/M transition of mitotic cell cycle
  • activation of MAPK activity
  • microtubule cytoskeleton organization
  • DNA replication
  • DNA repair

Molecular Function

  • virus receptor activity
  • chromatin binding
  • protein kinase activity
  • protein serine/threonine kinase activity
  • cyclin-dependent protein serine/threonine kinase activity

Cellular Component

  • cyclin-dependent protein kinase holoenzyme complex
  • nuclear chromosome, telomeric region
  • nucleus
  • nucleoplasm
  • cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000395284
Coding exons
7
Length
16522
Individuals with no LoFs
118842
Homozygous LoFs
0
Heterozygous LoFs
1
Defined
118843
p
0.00000421
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.97481510.3180.000007011948
Missense (PolyPhen)658.4950.10257804
Synonymous0.6144449.50.8890.00000213550
Loss of Function3.52014.50.007.03e-7196

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000320.000032rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

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}.;

Recessive Scores

pRec
0.822

Intolerance Scores

RVIS EVS
-0.1
RVIS percentile EVS
46.2

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
S
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.781

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumLowLow
Primary ImmunodeficiencyMediumLowMedium
CancerMediumLowMedium
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