MED9

Chr 17

mediator complex subunit 9

Also known as: MED25

The protein encoded by this gene is a component of the Mediator complex, which functions as a coactivator that bridges gene-specific regulatory proteins to the RNA polymerase II transcription machinery for regulated gene expression. Mutations cause neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy, which follows an autosomal recessive inheritance pattern. The disorder typically presents in infancy with developmental delays, seizures, and progressive brain volume loss.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.93
Clinical SummaryMED9
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.20) despite low pLI — interpret in context.
📋
ClinVar Variants
115 unique Pathogenic / Likely Pathogenic· 25 VUS of 144 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.93LOEUF
pLI 0.408
Z-score 1.69
OE 0.20 (0.070.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.79Z-score
OE missense 0.76 (0.620.93)
65 obs / 85.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.20 (0.070.93)
00.351.4
Missense OE0.76 (0.620.93)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 1 / 5.1Missense obs/exp: 65 / 85.7Syn Z: 0.05

ClinVar Variant Classifications

144 submitted variants in ClinVar

Classification Summary

Pathogenic115
VUS25
Likely Benign2
115
Pathogenic
25
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
115
0
115
Likely Pathogenic
0
0
0
0
0
VUS
0
20
5
0
25
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total0221200142

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

View in ClinVar →

Protein Context — Lollipop Plot

MED9 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗