NPRL3

Chr 16p13.3

NPR3 like, GATOR1 complex subunit

Aliases:: CGTHBA, RMD11, NPR3, MARE, HS-40
MANE:: ENST00000611875.5

OMIM: 600928 ↗NCBI: 8131 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

NPRL3 · Q12980

v62025-08-01

Predicted Aligned Error matrix for NPRL3 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

66.1/ 100

Low

569 residues

Confidence breakdown

Very high(≥ 90)0%
Confident(70–90)53%
Low(50–70)26%
Very low(< 50)21%

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
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Malformations of cortical development
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

familial focal epilepsy with variable foci
0.78
Seizure
0.50
hereditary disease
0.49
neurodegenerative disease
0.47
focal epilepsy
0.40
epilepsy, familial focal, with variable foci 1
0.37
Intellectual disability
0.27
benign thyroid gland neoplasm
0.22
epilepsy
0.17
sickle cell disease
0.11

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

Protein function (UniProt)

GATOR1 complex protein NPRL3

As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway (PubMed:23723238, PubMed:29590090, 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:29590090, 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)