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Protein / target

Cyclin-dependent kinase inhibitor 1

Encoded byCDKN1AP38936Homo sapiensSwiss-Prot
UniProt: P38936Ensembl: ENSG00000124762HGNC: HGNC:1784NCBI Gene: 1026
Small-molecule tractable
Druggability
Druggable Family
1
Research papers

Protein at a glance

Biological role

Protein serine/threonine kinase binding

Strongest disease association

Heart Failure

Via encoding gene CDKN1A · Genetic evidence · score 0.86

Research activity

Emerging research

1 papers · latest 2020

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest.

View complete UniProt function annotation

Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest (PubMed:9106657). Involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Also involved in p53-independent DNA damage-induced G2 arrest mediated by CREB3L1 in astrocytes and osteoblasts (By similarity). Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding (PubMed:11595739). Negatively regulates the CDK4- and CDK6-driven phosphorylation of RB1 in keratinocytes, thereby resulting in the release of E2F1 and subsequent transcription of E2F1-driven G1/S phase promoting genes (By similarity)

Subcellular location

CytoplasmNucleus
Domains and Gene Ontology detail (54)

Gene Ontology

  • Ccyclin-dependent protein kinase holoenzyme complex
  • Ccytoplasm
  • Ccytosol
  • Cnuclear body
  • Cnucleolus
  • Cnucleoplasm
  • Cnucleus
  • CPCNA-p21 complex
  • Cprotein-containing complex
  • Fcyclin binding
  • Fcyclin-dependent protein serine/threonine kinase inhibitor activity
  • Fmolecular function activator activity

164 aa · 18 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell-cycle regulationUniProt · GOCell proliferation & survivalGOKinase signallingUniProt · GO
View supporting evidence

Cell-cycle regulation

  • ·Plays an important role in controlling cell cycle progression and DNA damage-induced G2…
  • ·G1/S transition of mitotic cell cycle
  • ·negative regulation of G1/S transition of mitotic cell cycle
  • ·regulation of G1/S transition of mitotic cell cycle

Cell proliferation & survival

  • ·negative regulation of cell population proliferation

Kinase signalling

  • ·Plays an important role in controlling cell cycle progression and DNA damage-induced G2…
  • ·cyclin-dependent protein kinase holoenzyme complex
  • ·cyclin-dependent protein serine/threonine kinase inhibitor activity
  • ·protein kinase binding

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CDKN1A

Gene-level evidence surfaced through the gene CDKN1A that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Heart Failure
0.86Well supported

Genetic evidence dominant · Open Targets 0.52

Atrial Fibrillation
0.86Well supported

Genetic evidence dominant · Open Targets 0.53

Cardiomyopathy, Hypertrophic
0.79Well supported

Genetic evidence dominant · Open Targets 0.48

Urinary Bladder Neoplasms
0.56Moderately supported

Somatic mutation evidence dominant · Open Targets 0.60

Alzheimer's Disease
0.42Preliminary

Pathway evidence dominant · Open Targets 0.55 · no direct causal or clinical evidence

View evidence synthesis (5)
Heart FailureWell supported
0.86
agreement 0.72–1.00
Genetic98%Literature2%

Open Targets aggregate 0.52 · 2 independent evidence families

Atrial FibrillationWell supported
0.86
agreement 0.72–1.00
Genetic91%Literature9%

Open Targets aggregate 0.53 · 2 independent evidence families

Cardiomyopathy, HypertrophicWell supported
0.79
agreement 0.65–0.93
Genetic99%Literature1%

Open Targets aggregate 0.48 · 2 independent evidence families

Urinary Bladder NeoplasmsModerately supported
0.56
agreement 0.40–0.73
Somatic mutation80%Literature20%

Open Targets aggregate 0.60 · 2 independent evidence families

Alzheimer's DiseasePreliminary
0.42
agreement 0.24–0.60
Pathway75%Literature25%

Open Targets aggregate 0.55 · 2 independent evidence families · no direct causal or clinical evidence

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Urinary Bladder Neoplasms0.60
Neurodegenerative Diseases0.58
Alzheimer's Disease0.55
Parkinson's Disease0.53
Atrial Fibrillation0.53
Lysosomal Storage Diseases0.53
Multiple Sclerosis0.53
Heart Failure0.52
Cardiomyopathy, Hypertrophic0.48

Tractability

Small molecules — Emerging

Feasibility evidence (druggable family) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (4)
SM · Druggable FamilyPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of transcription factor activityToxCast

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Research activity

1 papers · to 2020

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure.703 cites

Shah S · Nature communications · 2020

Recent

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure.

Shah S · Nature communications · 2020

Europe PMC papers linked directly to this protein.