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GeneE
26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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MED1
mediator complex subunit 1
Chromosome 17 · 17q12
NCBI Gene: 5469Ensembl: ENSG00000125686.13HGNC: HGNC:9234UniProt: Q15648
276PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneTranscription Factor
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of erythrocyte differentiationpositive regulation of DNA-templated transcriptionmediator complexmembraneneurodegenerative diseaselysosomal storage diseaseParkinson diseaseAlzheimer disease
✦AI Summary

MED1 is a core component of the Mediator complex, a coactivator essential for regulated transcription of RNA polymerase II-dependent genes 123. MED1 functions as a transcriptional bridge, conveying signals from gene-specific regulatory proteins to basal RNA polymerase II machinery and facilitating preinitiation complex assembly 4. Mechanistically, MED1 contains intrinsically disordered regions that enable phase separation, forming nuclear condensates at super-enhancers where it concentrates transcriptional machinery to drive robust gene expression 5. MED1 also acts as a pH-sensitive regulator; acidic pH disrupts BRD4-MED1 condensates via histidine-rich regions, providing negative feedback on inflammatory responses 6. In disease contexts, MED1 dysfunction is implicated in pulmonary arterial hypertension, where decreased MED1 levels impair BMP/TGF-β signaling in endothelium 7. In cancer, MED1 enrichment at super-enhancers drives oncogene overexpression in head and neck squamous cell carcinoma, making it a therapeutic target 8. Additionally, MED1 participates in phase-separated transcriptional activation through interaction with pathway-specific transcription factors like TAZ 9. Clinically, understanding MED1's condensate dynamics and its role in cell-identity gene regulation offers insights for developing targeted therapies.

Sources cited
1
MED1 is a core Mediator complex component essential for RNA polymerase II transcription
PMID: 10406464
2
MED1 bridges regulatory proteins to basal transcription machinery
PMID: 11867769
3
MED1 facilitates preinitiation complex assembly
PMID: 12037571
4
MED1 role in TFIID-based PIC-Mediator assembly and CTD phosphorylation
PMID: 33958484
5
MED1 forms phase-separated condensates at super-enhancers to concentrate transcriptional apparatus
PMID: 29930091
6
Acidic pH disrupts BRD4-MED1 condensates, providing negative feedback on inflammation
PMID: 40680734
7
MED1 dysfunction in pulmonary hypertension through impaired BMP/TGF-β signaling in endothelium
PMID: 36252121
8
MED1 enrichment at super-enhancers drives oncogene expression in head and neck squamous cell carcinoma
PMID: 38443991
9
MED1 participates in TAZ-mediated phase-separated transcriptional activation
PMID: 32203417
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.58Moderate
lysosomal storage diseaseOpen Targets
0.49Moderate
Parkinson diseaseOpen Targets
0.46Moderate
Alzheimer diseaseOpen Targets
0.46Moderate
multiple sclerosisOpen Targets
0.46Moderate
neuroinflammatory disorderOpen Targets
0.46Moderate
asthmaOpen Targets
0.24Weak
urinary bladder carcinomaOpen Targets
0.16Weak
prostate cancerOpen Targets
0.12Weak
Familial prostate cancerOpen Targets
0.11Weak
neoplasmOpen Targets
0.11Weak
breast cancerOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.09Suggestive
cancerOpen Targets
0.09Suggestive
oral squamous cell carcinomaOpen Targets
0.07Suggestive
gliomaOpen Targets
0.06Suggestive
melanomaOpen Targets
0.06Suggestive
bladder calculusOpen Targets
0.06Suggestive
thyroid hormone metabolism, abnormal 1Open Targets
0.05Suggestive
Combined pituitary hormone deficiencies, genetic formsOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CDK9Protein interaction100%RPS15Protein interaction100%RPL35Protein interaction100%RPL11Protein interaction100%FAUProtein interaction100%RPS3Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
99%
Heart
73%
Ovary
54%
Lung
52%
Liver
43%
Gene Interaction Network
Click a node to explore
MED1CDK9RPS15RPL35RPL11FAURPS3
PROTEIN STRUCTURE
Preparing viewer…
PDB2O4J · 1.74 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.17Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.10 [0.06–0.17]
RankingsWhere MED1 stands among ~20K protein-coding genes
  • #1,320of 20,598
    Most Researched276 · top 10%
  • #301of 17,882
    Most Constrained (LOEUF)0.17 · top 5%
Genes detectedMED1
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
Coactivator condensation at super-enhancers links phase separation and gene control.
PMID: 29930091
Science · 2018
1.00
2
Regulation of inflammatory responses by pH-dependent transcriptional condensates.
PMID: 40680734
Cell · 2025
0.90
3
MED1 Regulates BMP/TGF-β in Endothelium: Implication for Pulmonary Hypertension.
PMID: 36252121
Circ Res · 2022
0.80
4
JMJD6 Rewires ATF4-Dependent Glutathione Metabolism to Confer Ferroptosis Resistance in SPOP-Mutated Prostate Cancer.
PMID: 39903850
Cancer Res · 2025
0.72
5
Structures of the human Mediator and Mediator-bound preinitiation complex.
PMID: 33958484
Science · 2021
0.70