MED13L

mediator complex subunit 13L

4 disorders 2 causative 1 no genetic record 1 untyped 12q24.21 gene with protein product

HGNC:22962 Monarch NCBI Gene 23389 ENSG00000123066 UniProt Q71F56 OMIM 608771

Previous symbols: THRAP2. Aliases: KIAA1025, TRAP240L.

Normal function · from ai-gene-review (Q71F56, commit 79fe13b38970) · AI-generated, not KB evidence

MED13L encodes Mediator of RNA polymerase II transcription subunit 13-like, a non-enzymatic subunit of the Mediator complex's CDK8 kinase module (CKM). The protein functions as a structural tether linking the CKM to core Mediator (cMED), regulating Pol II engagement and transcriptional programs. MED13L contains an Ago-like domain architecture with intrinsically disordered regions (IDRs) that can restrict or allow cMED interaction with Pol II/MED26, thereby modulating promoter-proximal events including initiation and pause-release. The protein localizes primarily to the nucleus and is required for Rb/E2F control of cell growth and neuronal dendritic development. Pathogenic variants cause MED13L syndrome characterized by developmental delay, intellectual disability, speech impairment, and congenital heart defects.

MED13L functions as a structural tether within the Mediator CDK8 kinase module (CKM), linking the CKM to core Mediator and regulating RNA polymerase II engagement at promoters through its intrinsically disordered regions.

molecular function: transcription coregulator activity · directly involved in: regulation of transcription by RNA polymerase II · locations: nucleoplasm · in complex: mediator complex

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Autosomal Dominant Non-Syndromic Intellectual Disability	causative de novo	mechanism: Disrupted Chromatin and Transcriptional Regulation
MED13L Syndrome	causative germline	mechanism: CKM hinge anchoring by MED13L; MED13L haploinsufficiency; MED13L missense destabilisation and mislocalisation; SCF-FBW7 control of MED13L abundance variant: MED13L c.2597C>T (p.Pro866Leu); MED13L c.2605C>T (p.Pro869Ser); MED13L c.6485C>T (p.Thr2162Met); MED13L de novo frameshift variants c.3765delC and c.607dupT; MED13L intragenic deletion of exons 3-10 (12q24.21); MED13L splice acceptor variant of exon 5 animal model: Danio rerio; Mus musculus dataset: geo:GSE298801
Mediator Complex Neurodevelopmental Disorder	untyped Causative	mechanism: CDK8 Kinase Module Dysfunction subtype: MED13L dataset: clinicaltrials:NCT01238250; geo:GSE277054; geo:GSE298801 phenotype: Autism Spectrum Disorder; Congenital Heart Defects; Corpus Callosum Anomalies; Hearing Impairment; Hypotonia; Intellectual Disability; Seizures; White Matter Abnormalities scoped to subtype: MED13L
MED13 Syndrome	no genetic record	mechanism: MED13/MED13L paralog redundancy animal model: Mus musculus dataset: geo:GSE298801

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
syndromic intellectual disability MONDO:0000508	AD	Definitive 2021-04-21	no dismech entry
congenital heart disease MONDO:0005453	AD	Limited 2024-02-12	Congenital Heart Disease not named

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.