MED25: Mediator Complex Subunit 25
A key transcriptional coactivator involved in development, disease, and cancer
Gene Information Card
| Symbol | MED25 |
|---|---|
| Full Name | Mediator Complex Subunit 25 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 81857 ncbi.nlm.nih.gov/gene/81857 |
| Ensembl ID | ENSG00000104973 |
| UniProt ID | Q71SY5 |
| OMIM ID | 610197 |
| HGNC ID | 28845 |
| Aliases | ARC92, PTOV2, ACID1, TCBAP0758 |
Description
MED25 encodes a subunit of the Mediator complex, a multiprotein coactivator required for RNA polymerase II transcription. MED25 bridges transcription factors and the basal transcription machinery, regulating genes involved in development, cell proliferation, and stress response. It interacts with VP16, p53, and other activators. Mutations in MED25 cause Charcot-Marie-Tooth disease type 2B2 (CMT2B2) and are implicated in cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease type 2B2 (CMT2B2) | Loss-of-function mutations in MED25 impair peripheral nerve myelination and axonal maintenance | OMIM #610197; PMID: 24700674 |
| Hereditary motor and sensory neuropathy | MED25 mutations disrupt Mediator complex function, leading to neuronal degeneration | ClinVar; PMID: 24700674 |
| Breast cancer | MED25 overexpression correlates with poor prognosis; may enhance ERα-mediated transcription | COSMIC; PMID: 23934149 |
| Prostate cancer | MED25 (PTOV2) promotes cell proliferation and invasion via androgen receptor signaling | COSMIC; PMID: 21947076 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Heart | 8.7 | Low |
| Liver | 6.2 | Low |
| Kidney | 9.1 | Low |
| Testis | 15.6 | Medium |
| Ovary | 11.4 | Medium |
| Breast | 10.2 | Medium |
| Prostate | 13.8 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.5 | Embryonic kidney; high expression |
| HeLa | 11.2 | Cervical carcinoma; moderate |
| MCF7 | 16.1 | Breast cancer; high |
| LNCaP | 15.3 | Prostate cancer; high |
| SH-SY5Y | 9.8 | Neuroblastoma; moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.509C>T (p.Pro170Leu) | Missense | Rare | Loss of function; associated with CMT2B2 |
| c.1045C>T (p.Arg349Trp) | Missense | Rare | Likely pathogenic; neuropathy |
| c.1246G>A (p.Glu416Lys) | Missense | Rare | Uncertain significance |
| c.1483C>T (p.Arg495*) | Nonsense | Very rare | Truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense and nonsense mutations in MED25 reduce Mediator complex assembly and transcriptional activation, leading to peripheral neuropathy (CMT2B2).
Gain of Function (GOF)
Not well documented; overexpression in cancer may confer gain-of-function by enhancing oncogenic transcription.
Dominant Negative (DN)
Some missense variants may act dominant-negative by disrupting Mediator complex integrity.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Mediator complex (Reactome: R-HSA-212436)
• Transcriptional regulation by TP53 (Reactome: R-HSA-3700989)
• Gene expression (Transcription) (Reactome: R-HSA-74160)
Protein Summary
MED25 is a 747-amino-acid protein (UniProt Q71SY5) containing a von Willebrand factor type A (vWA) domain and a coiled-coil region. It localizes to the nucleus and is a component of the Mediator complex. MED25 directly interacts with transcription factors such as VP16, p53, and ERα, facilitating RNA polymerase II recruitment. It is expressed in multiple tissues, with highest levels in testis and breast. Mutations cause Charcot-Marie-Tooth disease type 2B2, and overexpression is observed in breast and prostate cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MED25 Knockout HEK293 Cell Line | EDJ-KQ8968 | Human | 81857 | Details Get a Quote |
| MED25 Knockout A-549 Cell Line | EDJ-KQ36588 | Human | 81857 | Details Get a Quote |
| MED25 Knockout HCT 116 Cell Line | EDJ-KQ36590 | Human | 81857 | Details Get a Quote |
| MED25 Knockout HeLa Cell Line | EDJ-KQ36591 | Human | 81857 | Details Get a Quote |
