DEPDC5
Chr 22ARADDEP domain containing 5, GATOR1 subcomplex subunit
The protein functions as a component of the GATOR1 complex that inhibits the mTORC1 pathway by acting as a GTPase activating protein for Rag GTPases in response to amino acid depletion, thereby regulating cell growth and metabolism. Mutations cause autosomal dominant familial focal epilepsy with variable foci and developmental and epileptic encephalopathy through loss of function mechanisms that lead to mTORC1 hyperactivation. The pathogenic mechanism involves haploinsufficiency, where reduced GATOR1 complex function results in dysregulated mTOR signaling in neurons.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The Badonyi & Marsh model scores gain-of-function highest, but genomic evidence most strongly supports loss-of-function (haploinsufficiency) as the primary mechanism.
Literature Evidence
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
DEPDC5 · 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
External Resources
Links to major genomics databases and tools