Back to discover

Protein / target

Krueppel-like factor 4

Encoded byKLF4O43474Homo sapiensSwiss-Prot
UniProt: O43474Ensembl: ENSG00000136826HGNC: HGNC:6348NCBI Gene: 9314
Degrader-tractable
Druggability
UniProt Ubiquitination
2
Research papers

Protein at a glance

Biological role

Phosphatidylinositol 3-kinase regulator

Strongest disease association

Osteoarthritis, Hip

Via encoding gene KLF4 · Genetic evidence · score 0.67

Research activity

Emerging research

2 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

Transcription factor; can act both as activator and as repressor.

View complete UniProt function annotation

Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates the expression of key transcription factors during embryonic development. Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation. Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also function in skeletal and kidney development. Contributes to the down-regulation of p53/TP53 transcription

Subcellular location

NucleusCytoplasm
Domains and Gene Ontology detail (65)

Gene Ontology

  • Cchromatin
  • Ccytoplasm
  • Ceuchromatin
  • Cnucleoplasm
  • Cnucleus
  • Ctranscription regulator complex
  • Fbeta-catenin binding
  • Fchromatin DNA binding
  • FDNA-binding transcription activator activity, RNA polymerase II-specific
  • FDNA-binding transcription factor activity
  • FDNA-binding transcription factor activity, RNA polymerase II-specific
  • Fhistone deacetylase binding

513 aa · 55 kDa · 5 isoforms

Biological roles

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

Cell proliferation & survivalGOCell migrationGOCell-cycle regulationGOTranscriptional regulationUniProt · GOImmune signallingGO
View supporting evidence

Cell proliferation & survival

  • ·negative regulation of cell population proliferation

Cell migration

  • ·negative regulation of cell migration involved in sprouting angiogenesis

Cell-cycle regulation

  • ·negative regulation of G1/S transition of mitotic cell cycle

Transcriptional regulation

  • ·Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3'…
  • ·transcription regulator complex
  • ·DNA-binding transcription activator activity, RNA polymerase II-specific
  • ·DNA-binding transcription factor activity

Immune signalling

  • ·fat cell differentiation
  • ·negative regulation of inflammatory response
  • ·negative regulation of interleukin-8 production
  • ·negative regulation of response to cytokine stimulus

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 KLF4

Gene-level evidence surfaced through the gene KLF4that 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.

Breast Neoplasms
0.80Well supported

Genetic evidence dominant · Open Targets 0.47

Prostate carcinoma
0.79Well supported

Genetic evidence dominant · Open Targets 0.48

Cutaneous melanoma
0.68Moderately supported

Genetic evidence dominant · Open Targets 0.40

Osteoarthritis, Hip
0.67Moderately supported

Genetic evidence dominant · Open Targets 0.40

Meningioma
0.47Limited support

Somatic mutation evidence dominant · Open Targets 0.39

View evidence synthesis (5)
Breast NeoplasmsWell supported
0.80
agreement 0.69–0.90
Genetic55%Somatic mutation26%Literature13%RNA expression7%

Open Targets aggregate 0.47 · 4 independent evidence families

Prostate carcinomaWell supported
0.79
agreement 0.68–0.90
Genetic60%Somatic mutation27%Literature13%

Open Targets aggregate 0.48 · 3 independent evidence families

Cutaneous melanomaModerately supported
0.68
agreement 0.57–0.79
Genetic64%Somatic mutation35%Literature0%

Open Targets aggregate 0.40 · 3 independent evidence families

Osteoarthritis, HipModerately supported
0.67
agreement 0.55–0.79
Genetic100%

Open Targets aggregate 0.40 · 1 independent evidence family

MeningiomaLimited support
0.47
agreement 0.31–0.63
Somatic mutation76%Literature24%

Open Targets aggregate 0.39 · 2 independent evidence families

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
Neurodegenerative Diseases0.48
Prostate carcinoma0.48
Breast Neoplasms0.47
Osteoarthritis, Hip0.40
Cutaneous melanoma0.40
Meningioma0.39

Tractability

Protein degraders — Emerging

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

View underlying tractability evidence (2)
PR · UniProt UbiquitinationPR · Database Ubiquitination

Raw Open Targets tractability assessment buckets, by modality.

Research activity

2 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

Targeting cancer stem cell pathways for cancer therapy.1,354 cites

Yang L · Signal transduction and targeted therapy · 2020

In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming.694 cites

Ocampo A · Cell · 2016

Recent

Targeting cancer stem cell pathways for cancer therapy.

Yang L · Signal transduction and targeted therapy · 2020

In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming.

Ocampo A · Cell · 2016

Europe PMC papers linked directly to this protein.