NPRL2

Chr 3p21.31

NPR2 like, GATOR1 complex subunit

Aliases:: NPR2L, NPR2
MANE:: ENST00000232501.8

OMIM: 607072 ↗NCBI: 10641 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

NPRL2 · Q8WTW4

v62025-08-01

Predicted Aligned Error matrix for NPRL2 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

69.4/ 100

Low

380 residues

Confidence breakdown

Very high(≥ 90)0%
Confident(70–90)51%
Low(50–70)47%
Very low(< 50)2%

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, NOT imprinted
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
0.77
hereditary disease
0.51
Seizure
0.48
neurodegenerative disease
0.42
focal epilepsy
0.38
malignant pancreatic neoplasm
0.31
Neonatal respiratory distress
0.27
neoplasm
0.11
hepatocellular carcinoma
0.09
colorectal carcinoma
0.08

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

Protein function (UniProt)

GATOR1 complex protein NPRL2

Catalytic component of the GATOR1 complex, a multiprotein complex that functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway (PubMed:23723238, PubMed:29590090, PubMed:35338845, PubMed:38006878). 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 ubiquitinated and inhibited by GATOR2 (PubMed:23723238, PubMed:36528027). Within the GATOR1 complex, NPRL2 constitutes the catalytic subunit that mediates the GTPase activator activity and under methionine-sufficient conditions, the GTPase activator activity is inhibited by PRMT1 through methylation and consequently inducing timely mTORC1 activation (PubMed:27173016, PubMed:30651352, PubMed:35338845)