MED13L

Chr 12AD

mediator complex subunit 13L

Also known as: MRFACD, PROSIT240, THRAP2, TRAP240L

NCBI Gene: 23389 ENSG00000123066 UniProt: Q71F56 OMIM: 608771

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is a subunit of the Mediator complex, a large complex of proteins that functions as a transcriptional coactivator for most RNA polymerase II-transcribed genes. The encoded protein is involved in early development of the heart and brain. Defects in this gene are a cause of transposition of the great arteries, dextro-looped (DTGA).[provided by RefSeq, Jul 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.061 OMIM phenotype

Clinical Summary— MED13L

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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

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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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ClinVar Variants

306 unique Pathogenic / Likely Pathogenic· 591 VUS of 1753 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 →

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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

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.06LOEUF

pLI 1.000

Z-score 9.01

OE 0.02 (0.01–0.06)

Highly constrained

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

Missense Constraint?

3.69Z-score

OE missense 0.70 (0.66–0.74)

839 obs / 1198.6 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.02 (0.01–0.06)

0≤0.351.4

Missense OE?0.70 (0.66–0.74)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 2 / 98.5Missense obs/exp: 839 / 1198.6Syn Z: -0.20

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongMED13L-related intellectual disabilityLOFAD

This gene — mechanism propensity

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 · 80% of P/LP variants are LoF · LOEUF 0.06 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFAdditional three patients with MED13L haploinsufficiency syndrome were identified here in association with rare complications.1

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

References

1.PMID 28371282 ↗

ClinVar Variant Classifications

1753 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic192

Likely Pathogenic114

VUS591

Likely Benign595

Benign146

Conflicting77

192

Pathogenic

114

Likely Pathogenic

591

VUS

595

Likely Benign

146

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	175	6	11	0	192
Likely Pathogenic	70	40	4	0	114
VUS	5	560	23	3	591
Likely Benign	1	157	169	268	595
Benign	1	44	60	41	146
Conflicting	—				77
Total	252	807	267	312	1,715

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

View in ClinVar →

43 pathogenic / likely-pathogenic (of 60) ClinVar copy-number / structural variants overlap MED13L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →