{"entity":{"id":"nprl2","kind":"target","name":"NPRL2","aka":["NPR2 like, GATOR1 complex subunit","GATOR1 complex protein NPRL2","NPR2L","NPR2","TUSC4"],"tldr":"NPRL2 (GATOR1 complex protein NPRL2) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Pancreatic ductal adenocarcinoma.","summary":"Catalytic component of the GATOR1 complex, a multiprotein complex that functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway. 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 signalling. In the presence of abundant amino acids, the GATOR1 complex is ubiquitinated and inhibited by GATOR2.\n\nIntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Pancreas.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:24969","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:24969"},{"label":"UniProt Q8WTW4","url":"https://www.uniprot.org/uniprotkb/Q8WTW4/entry"},{"label":"NCBI Gene 10641","url":"https://www.ncbi.nlm.nih.gov/gene/10641"},{"label":"Ensembl ENSG00000114388","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000114388"}],"tags":["cancer-genes-wave"],"related":["intogen"],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it a loss-of-function (LoF) driver in 1 cohort. Evidence tier \"cohort-driver\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"NPRL2","role":["tumour-suppressor"],"evidenceTier":"cohort-driver","sources":[{"label":"HGNC HGNC:24969","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:24969","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q8WTW4","url":"https://www.uniprot.org/uniprotkb/Q8WTW4/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"IntOGen NPRL2","url":"https://www.intogen.org/search?gene=NPRL2","note":"driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:24969","ensembl":"ENSG00000114388","uniprot":"Q8WTW4","entrez":"10641","biology":"Catalytic component of the GATOR1 complex, a multiprotein complex that functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway. 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 signalling. In the presence of abundant amino acids, the GATOR1 complex is ubiquitinated and inhibited by GATOR2. 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. Suppresses Src-dependent tyrosine phosphorylation and activation of PDPK1 and its downstream signalling. Down-regulates PDPK1 kinase activity by interfering with tyrosine phosphorylation at 'Tyr-9', 'Tyr-373' and 'Tyr-376' residues. Location: Lysosome membrane (UniProt). Locus 3p21.31 (HGNC).","whereFound":["Pancreatic ductal adenocarcinoma: IntOGen driver in 1 cohort (PANCREAS)"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/nprl2/","neighbours":{"collection":[{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"}],"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}]}}