MED13L

Chr 12AD

mediator complex subunit 13L

Also known as: MRFACD, PROSIT240, THRAP2, TRAP240L

NCBI Gene: 23389ENSG00000123066UniProt: Q71F56

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]

Primary Disease Associations & Inheritance

Impaired intellectual development and distinctive facial features with or without cardiac defectsMIM #616789
AD
1
Active trials
333
Pathogenic / LP
1749
ClinVar variants
17
Pubs (1 yr)
3.7
Missense Z· constrained
0.06
LOEUF· LoF intolerant
Clinical Summary— MED13L
🧬
Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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.
📋
ClinVar Variants
333 Pathogenic / Likely Pathogenic· 599 VUS of 1749 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
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 OE0.02 (0.01–0.06)
0≤0.351.4
Missense OE0.70 (0.66–0.74)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 2 / 98.5Missense obs/exp: 839 / 1198.6Syn Z: -0.20
LOF
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 · 46% of P/LP variants are LoF · 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

1749 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic218
Likely Pathogenic115
VUS599
Likely Benign594
Benign149
Conflicting74
218
Pathogenic
115
Likely Pathogenic
599
VUS
594
Likely Benign
149
Benign
74
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
110
5
103
0
218
Likely Pathogenic
42
40
33
0
115
VUS
5
551
40
3
599
Likely Benign
1
155
172
266
594
Benign
1
46
60
42
149
Conflicting
—74
Total1597974083111,749

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

View in ClinVar →

MED13L · protein map & ClinVar variants

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

Gene2Phenotype Curations

MED13L-related intellectual disability

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients