MED13L

Chr 12AD

mediator complex subunit 13L

Also known as: MRFACD, PROSIT240, THRAP2, TRAP240L

The MED13L protein is a subunit of the Mediator complex that functions as a transcriptional coactivator for RNA polymerase II-transcribed genes and is involved in early heart and brain development. Mutations cause autosomal dominant intellectual disability with distinctive facial features and variable cardiac defects including transposition of the great arteries through a loss-of-function mechanism. The gene is highly intolerant to loss-of-function variants, consistent with its role in neurodevelopment.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.061 OMIM phenotype
Clinical SummaryMED13L
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Gene-Disease Validity (ClinGen)
congenital heart disease · ADLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

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.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — MED13L
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.06LOEUF
pLI 1.000
Z-score 9.01
OE 0.02 (0.010.06)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.69Z-score
OE missense 0.70 (0.660.74)
839 obs / 1198.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.02 (0.010.06)
00.351.4
Missense OE0.70 (0.660.74)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 2 / 98.5Missense obs/exp: 839 / 1198.6Syn Z: -0.20
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongMED13L-related intellectual disabilityLOFAD
DN
0.16100th %ile
GOF
0.2198th %ile
LOF
0.88top 5%

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

LOFprediction above median · 1 literature citation · LOEUF 0.06

Literature Evidence

LOFAdditional three patients with MED13L haploinsufficiency syndrome were identified here in association with rare complications.PMID:28371282

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

MED13L · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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