KDM4A
Lysine Demethylase 4A: A Key Epigenetic Regulator in Cancer and Development
Gene Information Card
| Symbol | KDM4A |
|---|---|
| Full Name | Lysine Demethylase 4A |
| Gene Type | Protein coding |
| Chromosomal Location | 1p34.1 |
| NCBI Gene ID | 9682 ncbi.nlm.nih.gov/gene/9682 |
| Ensembl ID | ENSG00000066135 |
| UniProt ID | O75164 |
| OMIM ID | 609765 |
| HGNC ID | 22978 |
| Aliases | JMJD2A, JHDM3A, KIAA0677 |
Description
KDM4A (lysine demethylase 4A) is a gene encoding a histone demethylase that specifically demethylates di- and tri-methylated lysine 9 and lysine 36 of histone H3 (H3K9me2/me3 and H3K36me2/me3). It acts as a transcriptional regulator by removing repressive histone marks, thereby promoting gene expression. KDM4A is involved in various cellular processes including DNA replication, cell cycle progression, and chromatin remodeling. Overexpression or amplification of KDM4A is frequently observed in multiple cancer types, contributing to tumorigenesis and metastasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | KDM4A overexpression leads to H3K9me3 demethylation at oncogene promoters, activating proliferation and invasion pathways. | ClinVar, COSMIC |
| Prostate Cancer | KDM4A amplification drives androgen receptor signaling and promotes castration-resistant growth. | COSMIC, NCBI Gene |
| Colorectal Cancer | KDM4A upregulation correlates with poor prognosis and promotes epithelial-mesenchymal transition (EMT). | COSMIC, ClinVar |
| Lung Cancer | KDM4A demethylates H3K9me3 at the promoter of oncogenes, enhancing cell migration and invasion. | COSMIC |
| Acute Myeloid Leukemia | KDM4A fusion proteins (e.g., NUP98-KDM4A) drive leukemogenesis through aberrant chromatin regulation. | COSMIC, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Bone Marrow | 8.3 | Medium |
| Lymph Node | 6.1 | Low |
| Brain | 4.2 | Low |
| Liver | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression |
| HeLa | 11.4 | High expression |
| MCF7 | 9.8 | Medium expression |
| A549 | 7.5 | Medium expression |
| K562 | 6.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1124G>A (p.Arg375Gln) | Missense | <0.1% | Altered substrate specificity; potential gain-of-function |
| c.1582C>T (p.Arg528Trp) | Missense | <0.1% | Reduced demethylase activity; loss-of-function |
| Amplification (1p34.1) | Copy number gain | 5-10% in breast cancer | Increased KDM4A expression; oncogenic |
| NUP98-KDM4A fusion | Structural variant | Rare in AML | Chimeric protein drives leukemogenesis |
Mutation functional classification
Loss of Function (LOF)
Missense mutations such as p.Arg528Trp reduce catalytic activity, impairing H3K9me3 demethylation and leading to altered gene expression.
Gain of Function (GOF)
Amplification of the KDM4A locus and certain missense mutations (e.g., p.Arg375Gln) enhance demethylase activity, promoting oncogenic transcription.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for KDM4A.
View complete mutation data：
Gene Ontology (GO)
| • Histone H3-K9 demethylase activity | • Histone H3-K36 demethylase activity |
| • Chromatin binding | • Nucleus |
| • Regulation of transcription | • DNA-templated |
| • Cell cycle | • DNA replication |
Pathways
• Chromatin modifying enzymes
• Transcriptional regulation by histone demethylation
• Oncogene-induced senescence
• DNA damage response
Protein Summary
KDM4A (also known as JMJD2A) is a 1064-amino acid protein containing a JmjC domain responsible for demethylase activity, two PHD-type zinc fingers, and two Tudor domains. It specifically demethylates H3K9me2/me3 and H3K36me2/me3, acting as a transcriptional activator. The protein is predominantly nuclear and plays roles in chromatin dynamics, cell cycle progression, and DNA repair. Dysregulation of KDM4A is implicated in multiple cancers, making it a potential therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KDM4A Knockout HEK293 Cell Line | EDJ-KQ3098 | Human | 9682 | Details Get a Quote |
| KDM4A Knockout HCT 116 Cell Line | EDJ-KQ23045 | Human | 9682 | Details Get a Quote |
| KDM4A Knockout A-549 Cell Line | EDJ-KQ24423 | Human | 9682 | Details Get a Quote |
| KDM4A Knockout HeLa Cell Line | EDJ-KQ24425 | Human | 9682 | Details Get a Quote |
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