DEPDC5

Chr 22q12.2-q12.3

DEP domain containing 5, GATOR1 subcomplex subunit

Aliases:: KIAA0645, DEP.5
MANE:: ENST00000651528.2

OMIM: 614191 ↗NCBI: 9681 ↗Ensembl ↗

Annotations refreshed 10 hours ago.

Predicted protein structure

AlphaFold predicted structure

DEPDC5 · O75140

v62025-08-01

Predicted Aligned Error matrix for DEPDC5 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

64.0/ 100

Low

1,603 residues

Confidence breakdown

Very high(≥ 90)18%
Confident(70–90)38%
Low(50–70)9%
Very low(< 50)36%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Disease associations (Open Targets)

familial focal epilepsy with variable foci
0.80
epilepsy, familial focal, with variable foci 1
0.77
developmental and epileptic encephalopathy 111
0.57
hereditary disease
0.55
Seizure
0.53
epilepsy
0.50
autosomal dominant nocturnal frontal lobe epilepsy
0.50
Rolandic epilepsy
0.50
self-limited epilepsy with centrotemporal spikes
0.50
focal epilepsy
0.46

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

GATOR1 complex protein DEPDC5

As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway (PubMed:23723238, PubMed:25457612, PubMed:29590090, PubMed:29769719, PubMed:31548394, PubMed:35338845). In response to amino acid depletion, the GATOR1 complex has GTPase activating protein (GAP) activity and strongly increases GTP hydrolysis by RagA/RRAGA (or RagB/RRAGB) within heterodimeric Rag complexes, thereby turning them into their inactive GDP-bound form, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling (PubMed:23723238, PubMed:25457612, PubMed:29590090, PubMed:29769719, PubMed:35338845). In the presence of abundant amino acids, the GATOR1 complex is negatively regulated by GATOR2, the other GATOR subcomplex, in this amino acid-sensing branch of the TORC1 pathway (PubMed:23723238, PubMed:25457612, PubMed:29769719). Within the GATOR1 complex, DEPDC5 mediates direct interaction with the nucleotide-binding pocket of small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD) and coordinates their nucleotide loading states by promoting RagA/RRAGA or RagB/RRAGB into their GDP-binding state and RagC/RRAGC or RagD/RRAGD into their GTP-binding state (PubMed:29590090, PubMed:35338845). However, it does not execute the GAP activity, which is mediated by NPRL2 (PubMed:29590090)