KLF4: A Key Regulator of Cell Differentiation and Tumor Suppression
Comprehensive gene card for Krüppel-like factor 4 (KLF4) — transcription factor, stem cell marker, and tumor suppressor
Gene Information Card
| Symbol | KLF4 |
|---|---|
| Full Name | Krüppel-like factor 4 (gut) |
| Gene Type | protein-coding |
| Chromosomal Location | 9q31.2 |
| NCBI Gene ID | 9314 ncbi.nlm.nih.gov/gene/9314 |
| Ensembl ID | ENSG00000136826 |
| UniProt ID | O43474 |
| OMIM ID | 602253 |
| HGNC ID | 6348 |
| Aliases | EZF, GKLF |
Description
KLF4 (Krüppel-like factor 4) is a zinc-finger transcription factor that plays a critical role in regulating cell proliferation, differentiation, apoptosis, and maintenance of stem cell pluripotency. It is widely expressed in epithelial tissues and acts as a tumor suppressor in many cancers, while also functioning as an oncogene in certain contexts. KLF4 is one of the Yamanaka factors used to reprogram somatic cells into induced pluripotent stem cells (iPSCs).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Loss of KLF4 expression leads to increased proliferation and reduced differentiation; promoter hypermethylation is common. | PMID: 15601829; COSMIC |
| Gastric cancer | KLF4 downregulation correlates with poor prognosis; acts as a tumor suppressor by inhibiting Wnt signaling. | PMID: 20023657; NCBI Gene |
| Breast cancer | KLF4 expression is reduced in invasive tumors; re-expression suppresses metastasis. | PMID: 19638577; ClinVar |
| Pancreatic cancer | KLF4 is frequently silenced by promoter methylation; loss promotes epithelial-mesenchymal transition. | PMID: 21502517; COSMIC |
| Prostate cancer | KLF4 expression is decreased in advanced disease; regulates androgen receptor signaling. | PMID: 22895138; OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Colon | 62.3 | High |
| Small intestine | 45.1 | High |
| Stomach | 38.7 | High |
| Esophagus | 30.2 | Medium |
| Skin | 25.6 | Medium |
| Lung | 18.4 | Medium |
| Breast | 12.1 | Low |
| Prostate | 10.5 | Low |
| Liver | 6.8 | Low |
| Brain | 2.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HCT116 (colon cancer) | 58.4 | High expression |
| MCF7 (breast cancer) | 22.1 | Moderate expression |
| A549 (lung cancer) | 15.3 | Low expression |
| HeLa (cervical cancer) | 12.7 | Low expression |
| K562 (leukemia) | 3.2 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | <1% | Reduced DNA-binding affinity; loss of transcriptional activity |
| c.1129G>A (p.Gly377Ser) | Missense | <1% | Impaired nuclear localization; partial loss of function |
| c.1300_1301insC (p.Gln434Profs*12) | Frameshift | <1% | Truncated protein; complete loss of function |
| c.1A>G (p.Met1Val) | Start loss | <1% | No protein translation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most KLF4 mutations in cancer are loss-of-function, including missense, frameshift, and nonsense variants that impair DNA binding, nuclear localization, or transcriptional activation.
Gain of Function (GOF)
Rare gain-of-function mutations have been reported in some hematologic malignancies, but are not well characterized.
Dominant Negative (DN)
No confirmed dominant-negative mutations have been described for KLF4.
View complete mutation data：
Gene Ontology (GO)
| • GO:0000978 – RNA polymerase II cis-regulatory region sequence-specific DNA binding | • GO:0000981 – DNA-binding transcription factor activity |
| • RNA polymerase II-specific | • GO:0005515 – protein binding |
| • GO:0005634 – nucleus | • GO:0006357 – regulation of transcription by RNA polymerase II |
| • GO:0008284 – positive regulation of cell population proliferation | • GO:0008285 – negative regulation of cell population proliferation |
| • GO:0030154 – cell differentiation | • GO:0045944 – positive regulation of transcription by RNA polymerase II |
| • GO:2000272 – negative regulation of signaling receptor activity |
Pathways
• Pluripotency of stem cells (KEGG: hsa04550)
• Transcriptional misregulation in cancer (KEGG: hsa05202)
• Signaling pathways regulating pluripotency of stem cells (Reactome: R-HSA-913531)
• p53 signaling pathway (Reactome: R-HSA-3700989)
Protein Summary
KLF4 is a 470-amino-acid protein containing three C-terminal C2H2-type zinc fingers that mediate sequence-specific DNA binding to GC-rich regions. It functions as both a transcriptional activator and repressor depending on cellular context and interacting partners. KLF4 is essential for maintaining epithelial homeostasis and is frequently silenced in gastrointestinal cancers. It also plays a key role in reprogramming somatic cells to pluripotency.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLF4 Knockout HEK293 Cell Line | EDJ-KQ2519 | Human | 9314 | Details Get a Quote |
| KLF4 Knockout A-549 Cell Line | EDJ-KQ23130 | Human | 9314 | Details Get a Quote |
| KLF4 Knockout HeLa Cell Line | EDJ-KQ23132 | Human | 9314 | Details Get a Quote |
| KLF4 Knockout HCT 116 Cell Line | EDJ-KQ21771 | Human | 9314 | Details Get a Quote |
| Klf4 Knockout HBZY-1 Cell Line | EDJ-KZ310 | Rat | 9314 | Details Get a Quote |
| KLF4 Knockout IPEC-J2 Cell Line | EDJ-KZ311 | Pig | 9314 | Details Get a Quote |
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