MED15

Chr 22

mediator complex subunit 15

Also known as: ARC105, CAG7A, CTG7A, PCQAP, TIG-1, TIG1, TNRC7

This protein is a component of the Mediator complex that serves as a coactivator for RNA polymerase II-dependent gene transcription and is required for cholesterol-dependent gene regulation. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. The gene is highly constrained against loss-of-function mutations (pLI >0.99), indicating that such variants are likely pathogenic when they occur.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.24
Clinical SummaryMED15
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.24LOEUF
pLI 1.000
Z-score 5.96
OE 0.13 (0.070.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.53Z-score
OE missense 0.67 (0.610.74)
319 obs / 474.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.13 (0.070.24)
00.351.4
Missense OE0.67 (0.610.74)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 7 / 54.5Missense obs/exp: 319 / 474.3Syn Z: -0.68
DN
0.2897th %ile
GOF
0.2298th %ile
LOF
0.83top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.24

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MED15 · 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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