MED25

Chr 19

mediator complex subunit 25

Also known as: ACID1, ARC92, BVSYS, CMT2B2, P78, PTOV2, TCBAP0758

NCBI Gene: 81857ENSG00000104973UniProt: Q9NWA0

This gene encodes a component of the transcriptional coactivator complex termed the Mediator complex. This complex is required for transcription of most RNA polymerase II-dependent genes. The encoded protein plays a role in chromatin modification and in preinitiation complex assembly. Mutations in this gene are associated with Charcot-Marie-Tooth disease type 2B2. [provided by RefSeq, Apr 2010]

479
ClinVar variants
5
Pathogenic / LP
0.00
pLI score
6
Active trials
Clinical Summary— MED25
🧬
Gene-Disease Validity (ClinGen)
Charcot-Marie-Tooth disease type 2B2 · ARDisputed

Disputed — evidence questions this relationship

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 220 VUS of 479 total submissions
💊
Clinical Trials
6 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (2)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.65LOEUF
pLI 0.000
Z-score 3.28
OE 0.43 (0.30–0.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.25Z-score
OE missense 0.83 (0.77–0.91)
380 obs / 455.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.43 (0.30–0.65)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.77–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.22
0≤1.21.6
LoF obs/exp: 17 / 39.1Missense obs/exp: 380 / 455.2Syn Z: -2.45

ClinVar Variant Classifications

479 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3
Likely Pathogenic2
VUS220
Likely Benign229
Benign16
Conflicting9
3
Pathogenic
2
Likely Pathogenic
220
VUS
229
Likely Benign
16
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
2
0
3
Likely Pathogenic
1
0
1
0
2
VUS
16
178
19
7
220
Likely Benign
0
1
92
136
229
Benign
0
0
15
1
16
Conflicting
—9
Total18179129144479

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MED25 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

MED25-related Basel-Vanagaite-Smirin-Yosef syndrome

definitive
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic, Clinical and Neuroradiological Spectrum of MED-Related Disorders: An Updated Review.
Fazio A et al.·Genes (Basel)
2025Review
Increasing evidence of pathogenic role of the Mediator (MED) complex in the development of cardiovascular diseases.
Napoli C et al.·Biochimie
2019Review
Improving the phenotype description of Basel-Vanagaite-Smirin-Yosef syndrome, MED25-related: polymicrogyria as a distinctive neuroradiological finding.
Maini I et al.·Neurogenetics
2021
Autosomal recessive Charcot-Marie-Tooth disease: from genes to phenotypes.
Tazir M et al.·J Peripher Nerv Syst
2013Review
Identification of the variant Ala335Val of MED25 as responsible for CMT2B2: molecular data, functional studies of the SH3 recognition motif and correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal models.
Leal A et al.·Neurogenetics
2009Functional
Screening of key genes related to the prognosis of mouse sepsis.
Chen M et al.·Biosci Rep
2020Functional
Molecular genetics of autosomal-recessive axonal Charcot-Marie-Tooth neuropathies.
Bernard R et al.·Neuromolecular Med
2006Review
Genotype and phenotype characteristics of West syndrome in 20 Vietnamese children: Two novel variants detected by next-generation sequencing.
Duc NM et al.·Epilepsy Res
2023
Charcot-Marie-Tooth disorders with an autosomal recessive mode of inheritance.
Kabzinska D et al.·Clin Neuropathol
2008Review
ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.
Montecchiani C et al.·Brain
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Toxoplasmosis in Neuropsychiatric Disorders

Toxoplasma Gondii Seroprevalence Among Children With Some Neuropsychiatric Disorders

NOT YET RECRUITING
NCT06980298Sohag UniversityStarted 2025-06
Immune ThrombocytopeniaSystem; Lupus Erythematosus

The Value of Interleukin-1β and Interleukin-33 Genetic Expression in the Pathogenesis and Differentiation of Primary ITP and SLE-Related Thrombocytopenia

NOT YET RECRUITING
NCT07298733Sohag UniversityStarted 2026-01-01
measuring gene expression
ITP - Immune Thrombocytopenia

"Cytotoxic T Lymphocyte-Associated Antigen-4 (CTLA-4) Gene Single-nucleotide Polymorphism in Primary Immune Thrombocytopenic Purpura in Children"

NOT YET RECRUITING
NCT07014904Sohag UniversityStarted 2025-08-20
Familial Mediterranean Fever

Health-related Quality of Life, Electrocardiographic and Holter Findings in Children With Familial Mediterranean Fever

ACTIVE NOT RECRUITING
NCT07128225Sohag UniversityStarted 2025-03-01
Primary Open Angle Glaucoma (POAG)

Association Between Matrix Metalloproteinase-9 Gene Polymorphism and Susceptibility to Primary Open Angle Glaucoma Patients in Sohag University Hospital

NOT YET RECRUITING
NCT07119905Sohag UniversityStarted 2026-06-01
genotyping assay by polymerase chain reaction
ISOLATION OF KLEB. by Culture on macConkey AgarAntibiotic Sensitivity Testing of Different Antibiotics According to Clsi 25Effect of Ceftazidime-Avibactam on Carbapenemase-Producing Klebsiella Pneumoniae

Effect of Ceftazidime-Avibactam on Carbapenemase-Producing Klebsiella Pneumoniae

NOT YET RECRUITING
NCT07369518Sohag UniversityStarted 2026-01
. - Genotypic detection of carbapenemase genes by conventional PCR.

External Resources

Links to major genomics databases and tools