MED22

Chr 9

mediator complex subunit 22

Also known as: MED24, SRB6, SURF5, surf-5

NCBI Gene: 6837ENSG00000148297UniProt: Q15528OMIM: 185641

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 Summary— MED22
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 41 VUS of 83 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.18LOEUF
pLI 0.000
Z-score 1.13
OE 0.65 (0.38–1.18)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.37Z-score
OE missense 0.91 (0.78–1.06)
112 obs / 123.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.65 (0.38–1.18)
0≤0.351.4
Missense OE0.91 (0.78–1.06)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
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

83 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic1
VUS41
Likely Benign2
35
Pathogenic
1
Likely Pathogenic
41
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
1
0
1
VUS
0
33
8
0
41
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Total03444179

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

View 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
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients