MED22

Chr 9

mediator 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.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
MultiplemechanismLOEUF 1.18
Clinical SummaryMED22
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.18LOEUF
pLI 0.000
Z-score 1.13
OE 0.65 (0.381.18)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.37Z-score
OE missense 0.91 (0.781.06)
112 obs / 123.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.65 (0.381.18)
00.351.4
Missense OE0.91 (0.781.06)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 8 / 12.3Missense obs/exp: 112 / 123.6Syn Z: -0.28
DN
0.6743th %ile
GOF
0.72top 25%
LOF
0.3647th %ile

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.

GOFprediction above median
DNprediction above median

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