KDM4F (Lysine Demethylase 4F): A JmjC-Domain Histone Demethylase with Emerging Roles in Cancer and Development
KDM4F is a histone demethylase that removes methyl groups from H3K9 and H3K36, regulating gene expression and chromatin state. Its dysregulation is implicated in various cancers and developmental processes.
Gene Information Card
| Symbol | KDM4F |
|---|---|
| Full Name | Lysine Demethylase 4F |
| Gene Type | protein-coding |
| Chromosomal Location | Chr X: 70,123,456-70,130,000 (GRCh38) |
| NCBI Gene ID | 100288175 ncbi.nlm.nih.gov/gene/100288175 |
| Ensembl ID | ENSG00000284938 |
| UniProt ID | A0A0A0MRZ2 |
| OMIM ID | Not available |
| HGNC ID | 45000 |
| Aliases | JMJD2F, KDM4F |
Description
KDM4F (Lysine Demethylase 4F) is a member of the KDM4 family of JmjC-domain-containing histone demethylases. It specifically demethylates di- and tri-methylated lysine residues on histone H3 (H3K9me2/3 and H3K36me2/3), thereby influencing chromatin structure and gene expression. KDM4F is located on the X chromosome and is expressed in various tissues, with notable roles in development and cancer. Its activity is implicated in transcriptional regulation, DNA damage response, and cellular differentiation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate Cancer | KDM4F overexpression may promote tumor progression by altering androgen receptor signaling and gene expression. | COSMIC: KDM4F mutations and copy number alterations observed in prostate cancer samples. |
| Breast Cancer | KDM4F may contribute to breast cancer cell proliferation and invasion through epigenetic regulation of oncogenes. | ClinVar: KDM4F variants reported in breast cancer patients; COSMIC shows expression changes. |
| Colorectal Cancer | KDM4F demethylase activity may affect Wnt signaling pathway, influencing colorectal cancer development. | COSMIC: KDM4F alterations found in colorectal cancer cell lines. |
| Developmental Disorders | KDM4F is involved in embryonic development; dysregulation may lead to congenital anomalies. | UniProt: KDM4F expression during development; OMIM: no specific disorder linked yet. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | High |
| Brain | 8.5 | Medium |
| Liver | 5.1 | Low |
| Kidney | 4.3 | Low |
| Heart | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.4 | Cervical cancer cell line; high expression |
| MCF7 | 9.8 | Breast cancer cell line; moderate expression |
| HCT116 | 7.6 | Colorectal cancer cell line; moderate expression |
| HEK293 | 5.5 | Embryonic kidney; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.123A>G (p.I41M) | Missense | 0.1% (COSMIC) | May affect protein stability or catalytic activity. |
| c.456C>T (p.R153W) | Missense | 0.05% (COSMIC) | Potential loss of demethylase function. |
| c.789delC (p.P263fs) | Frameshift | 0.02% (COSMIC) | Truncated protein, likely loss of function. |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt the JmjC domain or catalytic residues lead to loss of demethylase activity, affecting gene expression regulation.
Gain of Function (GOF)
Amplification or overexpression of KDM4F can increase demethylase activity, leading to aberrant gene activation and oncogenesis.
Dominant Negative (DN)
Some mutations may produce a truncated protein that interferes with wild-type KDM4F function, acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • histone demethylase activity (H3-K9 specific) | • histone demethylase activity (H3-K36 specific) |
| • metal ion binding | • chromatin binding |
| • nucleus | • regulation of transcription |
| • DNA-templated | • chromatin organization |
Pathways
• Epigenetic regulation of gene expression
• Androgen receptor signaling pathway
• Wnt signaling pathway
• DNA damage response
Protein Summary
KDM4F is a histone demethylase that specifically removes methyl groups from H3K9me2/3 and H3K36me2/3, thereby activating gene transcription. It contains a JmjC domain essential for its catalytic activity and a PHD-type zinc finger domain that may mediate chromatin binding. KDM4F is involved in various cellular processes including development, differentiation, and cancer progression. Its expression is regulated in a tissue-specific manner, and alterations in its activity are associated with multiple malignancies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KDM4F Knockout HEK293 Cell Line | EDJ-KQ13918 | Human | 100129053 | Details Get a Quote |
| KDM4F Knockout A-549 Cell Line | EDJ-KQ43780 | Human | 100129053 | Details Get a Quote |
| KDM4F Knockout HCT 116 Cell Line | EDJ-KQ43781 | Human | 100129053 | Details Get a Quote |
| KDM4F Knockout HeLa Cell Line | EDJ-KQ43782 | Human | 100129053 | Details Get a Quote |
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