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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
MED25
mediator complex subunit 25
Chromosome 19 Β· 19q13.33
NCBI Gene: 81857Ensembl: ENSG00000104973.19HGNC: HGNC:28845UniProt: M0QZQ2
77PubMed Papers
22Diseases
0Drugs
7Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTranscription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
transcription coactivator bindingprotein bindingnuclear retinoic acid receptor bindingnuclear retinoid X receptor bindingcongenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndromeneurodegenerative diseaseCharcot-Marie-Tooth disease type 2B2genetic disorder
✦AI Summary

MED25 is a subunit of the Mediator complex, a conserved transcriptional coactivator that bridges gene-specific regulatory proteins to RNA polymerase II machinery 1. As a component of the Mediator complex, MED25 functions as a scaffold for preinitiation complex assembly and is recruited to gene promoters through direct interactions with transcription factors, including retinoic acid receptors 2. MED25 contains an activator interaction domain (ACID) that serves as a docking site for transcriptional regulators, demonstrating conformational flexibility in binding diverse activators 3. Mutations in MED25 cause Basel-Vanagaite-Smirin-Yosef syndrome and Charcot-Marie-Tooth disease type 2B2, highlighting its essential role in neurological function 1. MED25 has been identified as a target for viral interference: respiratory syncytial virus NS1 protein binds MED25 ACID through dual interaction sites, potentially blocking access of host transcription factors and suppressing antiviral gene expression 34. Similarly, enterovirus 71 shares an epitope with MED25, suggesting cross-reactivity that may trigger autoimmune-mediated neurological complications 5. Increased MED25 peptide intensity has been detected in Alzheimer's disease plasma 6, though the functional significance requires clarification.

Sources cited
1
MED25 mutations are associated with genetic diseases including Charcot-Marie-Tooth disease and Basel-Vanagaite-Smirin-Yosef syndrome; role in neurological disease
PMID: 37516429
2
MED25 functions as a coactivator of estrogen receptor Ξ± through its C-terminal LXXLL motif and mediates transcriptional regulation of CYP2C9
PMID: 27273787
3
RSV NS1 protein binds MED25 ACID domain through dual binding interfaces; NS1-MED25 interaction regulates host gene transcription including ATF3-mediated genes
PMID: 40128225
4
RSV NS1 Ξ±/Ξ² core domain cooperatively binds MED25 ACID with nanomolar affinity; NS1-MED25 complex blocks transcription factor access to MED25, suppressing antiviral gene expression
PMID: 40920851
5
Enterovirus 71 VP1 shares a common epitope with human MED25; cross-reactive antibodies detected in EV71-infected patients may contribute to neurological disease through autoimmunity
PMID: 25826188
6
MED25 peptide precursor intensity is increased in Alzheimer's disease plasma compared to controls
PMID: 34182925
Disease Associationsβ“˜22
congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndromeOpen Targets
0.77Strong
neurodegenerative diseaseOpen Targets
0.54Moderate
Charcot-Marie-Tooth disease type 2B2Open Targets
0.51Moderate
genetic disorderOpen Targets
0.47Moderate
Tip-toe gaitOpen Targets
0.46Moderate
Charcot-Marie-Tooth disease type 2Open Targets
0.42Moderate
syndromic intellectual disabilityOpen Targets
0.37Weak
autosomal recessive non-syndromic intellectual disabilityOpen Targets
0.37Weak
Neurodevelopmental delayOpen Targets
0.33Weak
Neurodevelopmental disorderOpen Targets
0.30Weak
Charcot-Marie-Tooth diseaseOpen Targets
0.19Weak
melanomaOpen Targets
0.15Weak
neuroblastomaOpen Targets
0.15Weak
polyneuropathyOpen Targets
0.15Weak
autismOpen Targets
0.11Weak
Respiratory Syncytial Virus InfectionOpen Targets
0.03Suggestive
acromesomelic dysplasia 2AOpen Targets
0.03Suggestive
Acromesomelic dysplasia, Grebe typeOpen Targets
0.03Suggestive
AcheiropodiaOpen Targets
0.03Suggestive
acheiropodyOpen Targets
0.03Suggestive
Basel-Vanagaite-Smirin-Yosef syndromeUniProt
Charcot-Marie-Tooth disease, axonal, type 2B2UniProt
Pathogenic Variants7
NM_030973.4(MED25):c.418C>T (p.Arg140Trp)Pathogenic
not provided|Charcot-Marie-Tooth disease type 2|Congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 140
NM_030973.4(MED25):c.2T>G (p.Met1Arg)Likely pathogenic
Congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 1
NM_030973.4(MED25):c.781_791del (p.Pro261fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2022β†’ Residue 261
NM_030973.4(MED25):c.820-1G>ALikely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2020
NM_030973.4(MED25):c.1939C>T (p.Arg647Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2018β†’ Residue 647
NM_030973.4(MED25):c.1165del (p.Leu389fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2017β†’ Residue 389
NM_030973.4(MED25):c.116A>G (p.Tyr39Cys)Pathogenic
Congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome
β˜†β˜†β˜†β˜†2015β†’ Residue 39
View on ClinVar β†—
Related Genes
ZC3H13Protein interaction100%POLR2BProtein interaction100%POLR2FProtein interaction100%POLR2AProtein interaction100%POLR2JProtein interaction100%GTF2F2Protein interaction100%
Tissue Expression6 tissues
Ovary
100%
Lung
77%
Brain
52%
Bone Marrow
51%
Liver
37%
Heart
35%
Gene Interaction Network
Click a node to explore
MED25ZC3H13POLR2BPOLR2FPOLR2APOLR2JGTF2F2
PROTEIN STRUCTURE
Preparing viewer…
PDB9CCV Β· 2.53 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.87LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.70 [0.57–0.87]
RankingsWhere MED25 stands among ~20K protein-coding genes
  • #6,179of 20,598
    Most Researched77
  • #3,195of 5,498
    Most Pathogenic Variants7
  • #7,728of 17,882
    Most Constrained (LOEUF)0.87
Genes detectedMED25
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis Β· 2022
1.00
2
An Unexpected Encounter: Respiratory Syncytial Virus Nonstructural Protein 1 Interacts with Mediator Subunit MED25.
PMID: 36102648
J Virol Β· 2022
0.90
3
The plasma peptides of Alzheimer's disease.
PMID: 34182925
Clin Proteomics Β· 2021
0.80
4
Molecular basis for human respiratory syncytial virus transcriptional regulator NS1 interactions with MED25.
PMID: 40128225
Nat Commun Β· 2025
0.70
5
Mediator complex in neurological disease.
PMID: 37516429
Life Sci Β· 2023
0.60