NPRL3 Gene
NPRL3, GATOR1 Complex Subunit, Associated with Epilepsy and Cancer
Gene Information Card
| Symbol | NPRL3 |
|---|---|
| Full Name | NPRL3, GATOR1 Complex Subunit |
| Gene Type | protein-coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 8131 ncbi.nlm.nih.gov/gene/8131 |
| Ensembl ID | ENSG00000103174 |
| UniProt ID | Q96P20 |
| OMIM ID | 613197 |
| HGNC ID | 24924 |
| Aliases | CGORF32, MGC26594, NPRL3 |
Description
NPRL3 (NPR3-like, GATOR1 complex subunit) encodes a component of the GATOR1 complex, which negatively regulates the mTORC1 signaling pathway in response to amino acid deprivation. The GATOR1 complex, comprising DEPDC5, NPRL2, and NPRL3, acts as a GTPase-activating protein (GAP) for Rag GTPases, thereby suppressing mTORC1 activity. Loss-of-function mutations in NPRL3 lead to mTORC1 hyperactivation and are associated with focal epilepsy, focal cortical dysplasia, and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epilepsy, familial focal, with variable foci 3 (FFEVF3) | Loss-of-function mutations impair GATOR1 GAP activity, causing mTORC1 hyperactivation and neuronal migration defects | OMIM #613197; ClinVar |
| Focal cortical dysplasia type II | Somatic or germline NPRL3 mutations lead to mTOR pathway hyperactivation and dysplastic cortical lesions | OMIM #613197; PMID: 26285029 |
| Hepatocellular carcinoma | NPRL3 mutations or copy-number alterations contribute to mTORC1-driven tumorigenesis | COSMIC; PMID: 29127120 |
| Colorectal cancer | NPRL3 alterations identified in tumor sequencing, potentially activating mTOR signaling | COSMIC; PMID: 28138146 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Medium |
| Liver | 6.1 | Low |
| Kidney | 7.4 | Medium |
| Testis | 15.2 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.8 | High expression |
| SH-SY5Y | 11.2 | Medium expression |
| HepG2 | 9.5 | Medium expression |
| A549 | 7.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339*) | Nonsense | Rare | Loss of function; truncation of NPRL3 protein |
| c.487_488del (p.Leu163Valfs*12) | Frameshift deletion | Rare | Loss of function; premature termination |
| c.1250G>A (p.Arg417Gln) | Missense | Rare | Likely loss of function; disrupts GATOR1 complex assembly |
| c.1180C>T (p.Arg394Trp) | Missense | Rare | Loss of function; reduces GAP activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and missense mutations that impair GATOR1 GAP activity, leading to mTORC1 hyperactivation.
Gain of Function (GOF)
Not reported; NPRL3 acts as a tumor suppressor and negative regulator.
Dominant Negative (DN)
Not documented; mutations are typically loss-of-function with haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
Pathways
• mTOR signaling pathway (KEGG hsa04150)
• GATOR1 complex and amino acid sensing (Reactome R-HSA-9639288)
Protein Summary
NPRL3 is a 569-amino acid protein (UniProt Q96P20) that forms the GATOR1 complex with DEPDC5 and NPRL2. It contains a longin domain and is essential for the GAP activity toward RagA/B GTPases. The protein is ubiquitously expressed, with highest levels in testis and brain. Structural studies indicate that NPRL3 stabilizes the complex and is required for membrane localization.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NPRL3 Knockout HEK293 Cell Line | EDJ-KQ1165 | Human | 8131 | Details Get a Quote |
| NPRL3 Knockout A-549 Cell Line | EDJ-KQ19070 | Human | 8131 | Details Get a Quote |
| NPRL3 Knockout HCT 116 Cell Line | EDJ-KQ20419 | Human | 8131 | Details Get a Quote |
| NPRL3 Knockout HeLa Cell Line | EDJ-KQ20420 | Human | 8131 | Details Get a Quote |
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