MDM4 Gene (MDM4 Regulator of p53)
A key negative regulator of p53 tumor suppressor, frequently amplified in cancers.
Gene Information Card
| Symbol | MDM4 |
|---|---|
| Full Name | MDM4 regulator of p53 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q32.1 |
| NCBI Gene ID | 4194 ncbi.nlm.nih.gov/gene/4194 |
| Ensembl ID | ENSG00000112164 |
| UniProt ID | O15151 |
| OMIM ID | 602704 |
| HGNC ID | 6974 |
| Aliases | MDMX, MRP1, HDMX, MDP1 |
Description
MDM4 (also known as MDMX) is a nuclear protein that binds to and inhibits the transcriptional activation function of the tumor suppressor p53. It also modulates p53 stability by promoting its ubiquitination and degradation in cooperation with MDM2. MDM4 is frequently amplified or overexpressed in various cancers, leading to inactivation of p53 and contributing to tumorigenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Amplification/overexpression of MDM4 inhibits p53-mediated apoptosis and cell cycle arrest. | PMID: 20516151, COSMIC |
| Retinoblastoma | MDM4 amplification contributes to p53 inactivation in retinoblastoma tumors. | PMID: 17699751, COSMIC |
| Melanoma | MDM4 overexpression promotes melanoma cell survival by suppressing p53. | PMID: 22665060, COSMIC |
| Colorectal cancer | MDM4 overexpression correlates with poor prognosis and p53 inactivation. | PMID: 22538462, COSMIC |
| Lung cancer | MDM4 amplification leads to p53 pathway disruption in non-small cell lung cancer. | PMID: 23542178, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Lymph node | 8.2 | Medium |
| Breast | 6.1 | Low |
| Lung | 5.3 | Low |
| Colon | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 10.2 | High expression; p53 wild-type |
| A549 (lung cancer) | 7.5 | Moderate expression |
| HCT116 (colorectal cancer) | 6.9 | Moderate expression |
| HEK293 (embryonic kidney) | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Potential start loss; functional impact unknown |
| c.748C>T (p.Arg250*) | Nonsense | <0.1% | Truncation; loss of p53-binding domain |
| Amplification (copy number gain) | Copy number variation | ~5-10% in breast cancer | Increased MDM4 expression; p53 inactivation |
Mutation functional classification
Loss of Function (LOF)
Nonsense or frameshift mutations that truncate the p53-binding domain (e.g., p.Arg250*) reduce MDM4's ability to inhibit p53, potentially leading to increased p53 activity.
Gain of Function (GOF)
Gene amplification or overexpression enhances MDM4's inhibition of p53, promoting cell survival and tumor progression.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for MDM4.
View complete mutation data：
Gene Ontology (GO)
| • p53 binding (GO:0002039) | • protein binding (GO:0005515) |
| • nucleus (GO:0005634) | • cytoplasm (GO:0005737) |
| • negative regulation of apoptotic process (GO:0043066) | • protein stabilization (GO:0050821) |
Pathways
• p53 signaling pathway (KEGG: hsa04115)
• MDM2/MDM4-p53 pathway (Reactome: R-HSA-6804756)
Protein Summary
MDM4 (MDMX) is a 490-amino-acid protein containing an N-terminal p53-binding domain, a central acidic domain, a zinc finger domain, and a C-terminal RING finger domain. It forms heterodimers with MDM2 via the RING domain, enhancing MDM2-mediated ubiquitination and degradation of p53. MDM4 is essential for embryonic development and is tightly regulated; its overexpression is oncogenic.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MDM4 Knockout HEK293 Cell Line | EDJ-KQ5200 | Human | 4194 | Details Get a Quote |
| MDM4 Knockout HCT 116 Cell Line | EDJ-KQ28196 | Human | 4194 | Details Get a Quote |
| MDM4 Knockout HeLa Cell Line | EDJ-KQ28197 | Human | 4194 | Details Get a Quote |
| MDM4 Knockout A-549 Cell Line | EDJ-KQ62345 | Human | 4194 | Details Get a Quote |
| MDM4 (c.412-209T>C )Point Mutation in HAP1 Cell Line | EDC03537 | Human | 4194 | Details Get a Quote |
