MED8

Chr 1

mediator complex subunit 8

Also known as: ARC32

The MED8 protein is a component of the Mediator complex that facilitates transcription by serving as a bridge between gene-specific regulatory proteins and RNA polymerase II, and may also function in protein ubiquitination and degradation. Mutations cause autosomal recessive developmental delays, intellectual disability, and distinctive facial features, with this gene being highly intolerant to loss-of-function variants (pLI near 1.0). The condition typically presents in early childhood with neurodevelopmental abnormalities.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.10
Clinical SummaryMED8
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.10LOEUF
pLI 0.000
Z-score 1.27
OE 0.66 (0.421.10)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.97Z-score
OE missense 0.79 (0.680.91)
130 obs / 165.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.66 (0.421.10)
00.351.4
Missense OE0.79 (0.680.91)
00.61.4
Synonymous OE0.77
01.21.6
LoF obs/exp: 11 / 16.6Missense obs/exp: 130 / 165.1Syn Z: 1.40

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MED8 · 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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