MED22
Chr 9mediator complex subunit 22
Also known as: MED24, SRB6, SURF5, surf-5
The protein is a component of the Mediator complex that functions as a coactivator in the regulated transcription of RNA polymerase II-dependent genes by bridging gene-specific regulatory proteins with the basal transcription machinery. Mutations cause an autosomal dominant neurodevelopmental disorder through a predicted gain-of-function mechanism. The low pLI score (0.00008) and elevated LOEUF score (1.175) support tolerance to loss-of-function variants, consistent with the gain-of-function pathogenic mechanism.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
MED22 · 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
External Resources
Links to major genomics databases and tools