MED13

Chr 17AD

mediator complex subunit 13

Also known as: ARC250, DRIP250, HSPC221, MRD61, THRAP1, TRAP240

NCBI Gene: 9969ENSG00000108510UniProt: Q9UHV7

This gene encodes a component of the mediator complex (also known as TRAP, SMCC, DRIP, or ARC), a transcriptional coactivator complex thought to be required for the expression of almost all genes. The mediator complex is recruited by transcriptional activators or nuclear receptors to induce gene expression, possibly by interacting with RNA polymerase II and promoting the formation of a transcriptional pre-initiation complex. The product of this gene is proposed to form a sub-complex with MED12, cyclin C, and CDK8 that can negatively regulate transactivation by mediator. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 61MIM #618009
AD
0
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— MED13
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.03LOEUF
pLI 1.000
Z-score 9.19
OE 0.00 (0.00–0.03)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.62Z-score
OE missense 0.78 (0.74–0.82)
871 obs / 1117.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.03)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.74–0.82)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.09
0≤1.21.6
LoF obs/exp: 0 / 98.4Missense obs/exp: 871 / 1117.8Syn Z: -1.38

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

MED13 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MED13-related neurodevelopmental disorder

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal dominant 61

MIM #618009

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Penetrance, variable expressivity and monogenic neurodevelopmental disorders.
de Masfrand S et al.·Eur J Med Genet
2024
De Novo Variants in CNOT1, a Central Component of the CCR4-NOT Complex Involved in Gene Expression and RNA and Protein Stability, Cause Neurodevelopmental Delay.
Vissers LELM et al.·Am J Hum Genet
2020
MED13 mutation: A novel cause of developmental and epileptic encephalopathy with infantile spasms.
Trivisano M et al.·Seizure
2022Review
Could the MED13 mutations manifest as a Kabuki-like syndrome?
De Nardi L et al.·Am J Med Genet A
2021Case report
Genetic, Clinical and Neuroradiological Spectrum of MED-Related Disorders: An Updated Review.
Fazio A et al.·Genes (Basel)
2025Review
Mediator kinase module and human tumorigenesis.
Clark AD et al.·Crit Rev Biochem Mol Biol
2015Review
Expanding phenotype of MED13-associated syndrome presenting novel de novo missense variant in a patient with multiple congenital anomalies.
Tolmacheva E et al.·BMC Med Genomics
2024Case report
De novo mutations in MED13, a component of the Mediator complex, are associated with a novel neurodevelopmental disorder.
Snijders Blok L et al.·Hum Genet
2018
MED13-dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver.
Baskin KK et al.·EMBO Mol Med
2014
Increasing evidence of pathogenic role of the Mediator (MED) complex in the development of cardiovascular diseases.
Napoli C et al.·Biochimie
2019Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Med13 is involved in the radial migration and contralateral projection of cortical neurons via PlxnA4.
Li ZX et al.·Commun Biol
2026
miR-4326 predicts adverse outcomes of triple-negative breast cancer and regulates cell growth and motility through modulating MED13.
Wang W et al.·World J Surg Oncol
2026🔓 Open Access
Intellectual Developmental Disorder of Autosomal Dominant 61 Caused by a MED13 Variant Presenting With Congenital Unilateral Sensorineural Hearing Loss: A Case Report.
Pinto Alberto K et al.·Cureus
2025🔓 Open AccessCase report
Mitochondrial dysfunction in MED13 variant-associated disease: a case of infantile spasms, cardiomyopathy and hepatomegaly.
Harada M et al.·Hum Genome Var
2025🔓 Open Access
A novel frameshift variant in the MED13 gene causing intellectual developmental disorder-61 in a Chinese family.
Yang Q et al.·Front Pediatr
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools