HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
27 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
KLF6
KLF transcription factor 6
Chromosome 10 · 10p15.2
NCBI Gene: 1316Ensembl: ENSG00000067082.16HGNC: HGNC:2235UniProt: D3GC14
216PubMed Papers
22Diseases
0Drugs
6Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription Factor
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleoplasmnucleolusDNA-binding transcription activator activity, RNA polymerase II-specificprotein bindingprostate carcinomaschizophreniagastric cancerprostate cancer
✦AI Summary

KLF6 is a zinc-finger transcription factor that acts as a transcriptional activator binding GC box motifs 1. Primary functions include regulation of cellular differentiation and proliferation across multiple tissue contexts. In keratinocytes, KLF6 maintains cell proliferation and suppresses inflammation and senescence during skin aging 2. KLF6 regulates melanosome maturation and pigmentation in melanocytes 3, and in early embryonic development, it participates in a BMP4/Nodal-KLF6 axis controlling trophectoderm epithelial morphogenesis 4. In hematopoietic stem cells, KLF6 downregulation impairs differentiation and increases colony-forming potential, suggesting its role in maintaining normal hematopoietic function 5. Mechanistically, KLF6 transcriptionally regulates QKI-5 expression to suppress TGF-β signaling and epithelial-mesenchymal transition in lung adenocarcinoma 6. In diabetic kidney disease, podocyte-specific KLF6 induction triggers ApoJ secretion to activate CaMK1D signaling in proximal tubules, attenuating disease progression 1. KLF6 also regulates macrophage polarization through STAT3 signaling, with therapeutic implications for liver fibrosis 7. In intestinal immunity, KLF6 expression in pathogenic T cells promotes epithelial transformation through T-BET-dependent mechanisms 8. Clinically, KLF6 dysregulation associates with multiple cancers and age-related diseases.

Sources cited
1
KLF6 inhibition in keratinocytes compromises cell proliferation and increases inflammation and cellular senescence during skin aging
PMID: 33238152
2
KLF6 participates in BMP4/Nodal-KLF6 axis that fine-tunes trophoblast epithelial morphogenesis and implantation
PMID: 29720634
3
KLF6 functions as a transcription factor regulating melanosome maturation and pigmentation in vivo
PMID: 37561850
4
KLF6 is a zinc-finger binding transcription factor; podocyte-specific KLF6 triggers ApoJ release to activate CaMK1D signaling in proximal tubules
PMID: 39271683
5
KLF6 is epigenetically downregulated in aging hematopoietic stem cells; KLF6 downregulation results in impaired differentiation and increased colony-forming potential
PMID: 31085557
6
KLF6 is targeted by miR-148a in macrophages; KLF6 suppression inhibits STAT3 pathway and modulates macrophage polarization in liver fibrosis
PMID: 35858897
7
KLF6 transcriptionally regulates QKI-5, which post-transcriptionally degrades TGFβR1 mRNA to suppress TGF-β signaling and EMT
PMID: 33769671
8
KLF6 expression in intestinal T cells promotes epithelial transformation through T-BET-dependent interferon-γ production
PMID: 39060651
Disease Associationsⓘ22
prostate carcinomaOpen Targets
0.56Moderate
schizophreniaOpen Targets
0.47Moderate
gastric cancerOpen Targets
0.46Moderate
prostate cancerOpen Targets
0.38Weak
carcinoma of liver and intrahepatic biliary tractOpen Targets
0.37Weak
cutaneous melanomaOpen Targets
0.37Weak
Endometrial Endometrioid AdenocarcinomaOpen Targets
0.37Weak
nodular melanomaOpen Targets
0.37Weak
superficial spreading melanomaOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.37Weak
melanomaOpen Targets
0.32Weak
hepatocellular carcinomaOpen Targets
0.30Weak
complex regional pain syndromeOpen Targets
0.30Weak
chronic lymphocytic leukemiaOpen Targets
0.30Weak
lung adenocarcinomaOpen Targets
0.29Weak
gastric carcinomaOpen Targets
0.28Weak
multiple myelomaOpen Targets
0.28Weak
head and neck squamous cell carcinomaOpen Targets
0.28Weak
lung carcinomaOpen Targets
0.28Weak
breast ductal adenocarcinomaOpen Targets
0.28Weak
Gastric cancerUniProt
Prostate cancerUniProt
Pathogenic Variants6
NM_001300.6(KLF6):c.465C>A (p.Ser155Arg)Pathogenic
Gastric cancer
☆☆☆☆2005→ Residue 155
NM_001300.6(KLF6):c.346T>C (p.Ser116Pro)Pathogenic
Prostate cancer, somatic
☆☆☆☆2001→ Residue 116
NM_001300.6(KLF6):c.410C>A (p.Ser137Ter)Pathogenic
Prostate cancer, somatic
☆☆☆☆2001→ Residue 137
NM_001300.6(KLF6):c.368C>A (p.Ala123Asp)Pathogenic
Prostate cancer, somatic
☆☆☆☆2001→ Residue 123
NM_001300.6(KLF6):c.190T>C (p.Trp64Arg)Pathogenic
Prostate cancer, somatic
☆☆☆☆2001→ Residue 64
NM_001300.6(KLF6):c.506T>C (p.Leu169Pro)Pathogenic
Prostate cancer, somatic
☆☆☆☆2001→ Residue 169
View on ClinVar ↗
Related Genes
SP1Protein interaction99%TP53Protein interaction95%JUNProtein interaction92%ATF3Protein interaction77%DUSP1Protein interaction77%TCF3Shared pathway33%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
62%
Liver
18%
Ovary
18%
Heart
17%
Brain
16%
Gene Interaction Network
Click a node to explore
KLF6SP1TP53JUNATF3DUSP1TCF3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q99612
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.11Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.00 [0.00–0.11]
RankingsWhere KLF6 stands among ~20K protein-coding genes
  • #1,921of 20,598
    Most Researched216 · top 10%
  • #3,305of 5,498
    Most Pathogenic Variants6
  • #81of 17,882
    Most Constrained (LOEUF)0.11 · top 1%
Genes detectedKLF6
Sources retrieved27 papers
Response time—
📄 Sources
27▼
1
A Single-Cell Transcriptomic Atlas of Human Skin Aging.
PMID: 33238152
Dev Cell · 2021
1.00
2
Blastocyst-like structures generated solely from stem cells.
PMID: 29720634
Nature · 2018
0.90
3
A genome-wide genetic screen uncovers determinants of human pigmentation.
PMID: 37561850
Science · 2023
0.80
4
The chromatin landscape of healthy and injured cell types in the human kidney.
PMID: 38199997
Nat Commun · 2024
0.72
5
Podocyte-specific KLF6 primes proximal tubule CaMK1D signaling to attenuate diabetic kidney disease.
PMID: 39271683
Nat Commun · 2024
0.70