KLF6 Gene: Kruppel Like Factor 6 - Structure, Function, and Disease Associations
A comprehensive overview of the KLF6 gene, including its genomic context, protein function, expression patterns, and clinical significance in cancer and other diseases.
Gene Information Card
| Symbol | KLF6 |
|---|---|
| Full Name | Kruppel like factor 6 |
| Gene Type | protein coding |
| Chromosomal Location | 10p15.2 |
| NCBI Gene ID | 1316 ncbi.nlm.nih.gov/gene/1316 |
| Ensembl ID | ENSG00000067082 |
| UniProt ID | Q99612 |
| OMIM ID | 602053 |
| HGNC ID | 6348 |
| Aliases | CPBP, ST12, BCD1, PAC1, ZF9 |
Description
KLF6 (Kruppel like factor 6) is a tumor suppressor gene encoding a zinc finger transcription factor that regulates cell proliferation, differentiation, and apoptosis. It is frequently inactivated in various cancers, including prostate, hepatocellular, and colorectal cancers. KLF6 is located on chromosome 10p15.2 and is involved in multiple signaling pathways, including TGF-beta and p53. Its protein product binds to GC-rich promoter regions to modulate gene expression. Loss of KLF6 function contributes to tumor progression, making it a key target for cancer research.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate cancer | Loss of heterozygosity and somatic mutations lead to reduced tumor suppressor activity, promoting cell proliferation and invasion. | Multiple studies, including those in COSMIC and ClinVar, report KLF6 mutations in prostate cancer. |
| Hepatocellular carcinoma | Reduced KLF6 expression and mutations impair its ability to inhibit cell cycle progression and induce apoptosis. | Evidence from NCBI Gene and OMIM indicates KLF6 alterations in liver cancer. |
| Colorectal cancer | KLF6 inactivation via mutations or promoter methylation contributes to tumorigenesis by deregulating Wnt signaling. | ClinVar and COSMIC list KLF6 variants associated with colorectal cancer. |
| Gastric cancer | KLF6 downregulation is linked to increased cell proliferation and metastasis. | Studies in NCBI and OMIM document KLF6 involvement in gastric cancer. |
| Non-small cell lung cancer | Somatic mutations and reduced expression of KLF6 are observed, affecting cell cycle control. | COSMIC database includes KLF6 mutations in lung cancer samples. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 20.1 | High |
| Kidney | 15.3 | Medium |
| Lung | 12.8 | Medium |
| Prostate | 10.5 | Medium |
| Colon | 8.9 | Low |
| Brain | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 18.5 | High expression; used in hepatocellular carcinoma studies. |
| A549 (lung) | 14.2 | Moderate expression; relevant for lung cancer research. |
| PC3 (prostate) | 11.7 | Moderate expression; prostate cancer cell line. |
| MCF7 (breast) | 7.3 | Low expression; breast cancer cell line. |
| HeLa (cervical) | 6.8 | Low expression; cervical cancer cell line. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.IVS1-27G>A | Splice site variant | ~5% in prostate cancer | Alters splicing, leading to reduced KLF6 protein and loss of tumor suppressor function. |
| p.Pro232Leu | Missense | Rare (<1%) | Impairs DNA binding and transcriptional activity. |
| p.Arg243His | Missense | Rare (<1%) | Reduces nuclear localization and transcriptional regulation. |
| p.Leu250Val | Missense | Rare (<1%) | Affects zinc finger domain, reducing DNA binding. |
| p.Gln260Ter | Nonsense | Rare (<1%) | Truncates protein, leading to loss of function. |
Mutation functional classification
Loss of Function (LOF)
Most KLF6 mutations are loss-of-function, reducing or abolishing its tumor suppressor activity. This occurs via impaired DNA binding, altered splicing, or protein truncation.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported for KLF6. Some splice variants may have dominant-negative effects, but these are not classified as gain-of-function.
Dominant Negative (DN)
Certain KLF6 splice variants, such as KLF6-SV1, can act in a dominant-negative manner, inhibiting the full-length KLF6 protein and promoting tumor progression.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • zinc ion binding | • regulation of transcription by RNA polymerase II |
| • negative regulation of cell population proliferation | • positive regulation of apoptotic process |
| • cell differentiation | • response to transforming growth factor beta |
Pathways
• TGF-beta signaling pathway
• p53 signaling pathway
• Wnt signaling pathway
• Cell cycle regulation
• Apoptosis regulation
Protein Summary
The KLF6 protein is a 283-amino acid transcription factor containing three C-terminal C2H2-type zinc finger domains that mediate sequence-specific DNA binding to GC-rich motifs. It regulates the expression of genes involved in cell cycle arrest, apoptosis, and differentiation. KLF6 interacts with other proteins, including p53 and TGF-beta signaling components, to exert its tumor suppressor effects. Post-translational modifications and alternative splicing generate multiple isoforms with distinct functions. Loss of KLF6 function is a common event in cancer, highlighting its critical role in maintaining cellular homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLF6 Knockout HEK293 Cell Line | EDJ-KQ2994 | Human | 1316 | Details Get a Quote |
| KLF6 Knockout A-549 Cell Line | EDJ-KQ24183 | Human | 1316 | Details Get a Quote |
| KLF6 Knockout HCT 116 Cell Line | EDJ-KQ24184 | Human | 1316 | Details Get a Quote |
| KLF6 Knockout HeLa Cell Line | EDJ-KQ24185 | Human | 1316 | Details Get a Quote |
| Klf6 Knockout HBZY-1 Cell Line | EDJ-KZ312 | Rat | 1316 | Details Get a Quote |
