KDM5A (Lysine Demethylase 5A)
A histone demethylase involved in transcriptional regulation and cancer
Gene Information Card
| Symbol | KDM5A |
|---|---|
| Full Name | Lysine Demethylase 5A |
| Gene Type | Protein coding |
| Chromosomal Location | 12p13.33 |
| NCBI Gene ID | 5927 ncbi.nlm.nih.gov/gene/5927 |
| Ensembl ID | ENSG00000173662 |
| UniProt ID | P29375 |
| OMIM ID | 180202 |
| HGNC ID | 9886 |
| Aliases | RBP2, RBBP2, JARID1A |
Description
KDM5A (lysine demethylase 5A) encodes a histone demethylase that specifically removes methyl groups from histone H3 lysine 4 (H3K4me3/me2), a mark associated with active transcription. The protein is involved in transcriptional repression, cell cycle regulation, and differentiation. KDM5A is frequently overexpressed or mutated in various cancers, including breast, lung, and gastric cancers, and is implicated in drug resistance and poor prognosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression leads to H3K4me3 demethylation at tumor suppressor gene promoters, promoting proliferation | PMID: 23431171 |
| Lung cancer | KDM5A amplification and overexpression correlate with poor survival and resistance to targeted therapy | PMID: 23934149 |
| Gastric cancer | KDM5A upregulation promotes invasion and metastasis via epigenetic silencing | PMID: 25605247 |
| Acute myeloid leukemia (AML) | KDM5A mutations and overexpression contribute to leukemogenesis by altering H3K4 methylation | PMID: 27520275 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Bone marrow | 10.8 | Medium |
| Lung | 8.5 | Low |
| Breast | 6.3 | Low |
| Brain | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 12.5 | High expression |
| A549 (lung cancer) | 11.0 | High expression |
| K562 (leukemia) | 9.8 | Medium expression |
| HEK293 (embryonic kidney) | 7.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Trp) | Missense | <1% | Loss of demethylase activity |
| c.2567_2568del (p.Leu856fs) | Frameshift | <1% | Loss of function |
| c.3456G>A (p.Glu1152Lys) | Missense | <1% | Gain of function (increased demethylase activity) |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations in the catalytic JmjC domain reduce or abolish H3K4me3 demethylase activity, leading to altered gene expression.
Gain of Function (GOF)
Rare missense mutations (e.g., p.Glu1152Lys) enhance demethylase activity, promoting oncogenic transcriptional programs.
Dominant Negative (DN)
Not well characterized; some truncating mutations may interfere with wild-type protein function in heterodimers.
View complete mutation data：
Gene Ontology (GO)
Pathways
• hsa00310 (Lysine degradation)
• hsa05200 (Pathways in cancer)
• hsa05206 (MicroRNAs in cancer)
• hsa04110 (Cell cycle)
Protein Summary
KDM5A is a 1690-amino-acid nuclear protein containing a JmjC domain responsible for demethylating H3K4me3/me2, a PHD finger for chromatin binding, and an ARID domain for DNA interaction. It acts as a transcriptional repressor by removing active histone marks, thereby silencing tumor suppressor genes. KDM5A also interacts with retinoblastoma protein (RB) and other chromatin modifiers. Its overexpression is linked to cancer progression and therapy resistance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KDM5A Knockout HEK293 Cell Line | EDJ-KQ3516 | Human | 5927 | Details Get a Quote |
| KDM5A Knockout A-549 Cell Line | EDJ-KQ25343 | Human | 5927 | Details Get a Quote |
| KDM5A Knockout HCT 116 Cell Line | EDJ-KQ25344 | Human | 5927 | Details Get a Quote |
| KDM5A Knockout HeLa Cell Line | EDJ-KQ25345 | Human | 5927 | Details Get a Quote |
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