MED4
Chr 13mediator complex subunit 4
Also known as: ARC36, DRIP36, HSPC126, TRAP36, VDRIP
The protein is a component of the Mediator complex that functions as a coactivator and scaffold for RNA polymerase II transcription, facilitating communication between gene-specific regulatory proteins and the basal transcription machinery. Mutations cause neurodevelopmental disorders with intellectual disability, developmental delay, and behavioral abnormalities, following an autosomal dominant inheritance pattern. This gene is not highly constrained against loss-of-function variants, suggesting the associated phenotypes may arise through other molecular mechanisms.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MED4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools