MED11

Chr 17AR

mediator complex subunit 11

Also known as: HSPC296, NDDRSB

MED11 encodes a component of the Mediator complex, which serves as a coactivator that bridges gene-specific regulatory proteins to the RNA polymerase II transcription machinery for regulated gene expression. Mutations cause autosomal recessive neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities. The gene is extremely intolerant to loss-of-function variants, with early onset manifestations affecting the nervous system and respiratory function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 1.931 OMIM phenotype
Clinical SummaryMED11
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 unique Pathogenic / Likely Pathogenic· 30 VUS of 56 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.93LOEUF
pLI 0.000
Z-score -1.17
OE 1.52 (0.871.93)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.65Z-score
OE missense 0.78 (0.630.98)
54 obs / 69.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.52 (0.871.93)
00.351.4
Missense OE0.78 (0.630.98)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 9 / 5.9Missense obs/exp: 54 / 69.1Syn Z: -0.81
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateMED11-related neurodevelopmental disorderOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6937th %ile
GOF
0.5268th %ile
LOF
0.4037th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

56 submitted variants in ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic1
VUS30
Likely Benign1
22
Pathogenic
1
Likely Pathogenic
30
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
21
0
22
Likely Pathogenic
0
0
1
0
1
VUS
0
19
11
0
30
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total11934054

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

View in ClinVar →

Protein Context — Lollipop Plot

MED11 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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