MED21
Chr 12mediator complex subunit 21
Also known as: SRB7, SURB7, hSrb7
The encoded protein is a component of the Mediator complex that functions as a coactivator in the regulated transcription of nearly all RNA polymerase II-dependent genes, serving as a bridge between gene-specific regulatory proteins and the basal transcription machinery. Mutations cause autosomal recessive intellectual disability with distinctive facial features and variable developmental delays. The gene shows tolerance to loss-of-function variants in the general population.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
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
50 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 32 | 0 | 32 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 13 | 1 | 0 | 14 |
Likely Benign | 0 | 0 | 0 | 0 | 0 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 13 | 34 | 0 | 47 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MED21 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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