MED12
Chr XXLDXLRmediator complex subunit 12
Also known as: ARC240, CAGH45, FGS1, HDKR, HOPA, Kto, MED12S, OHDOX
The MED12 protein is essential for activating CDK8 kinase within the Mediator complex, which regulates transcription initiation and reinitiation rates by modulating interactions between Mediator and RNA polymerase II. Loss-of-function mutations cause multiple X-linked intellectual disability syndromes including Opitz-Kaveggia syndrome (FG syndrome), Lujan-Fryns syndrome, Ohdo syndrome, and Hardikar syndrome. The gene shows extreme intolerance to loss-of-function variants and follows X-linked inheritance patterns.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Extremely missense-constrained (top ~0.01%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
MED12 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools