The function of the encoded protein is not known. [provided by RefSeq, Aug 2011] See more...

Aliases for NPRL3 Gene

Aliases for NPRL3 Gene

  • NPR3 Like, GATOR1 Complex Subunit 2 3 5
  • CGTHBA 2 3 4
  • MARE 2 3 4
  • Alpha-Globin Regulatory Element-Containing Gene Protein 3 4
  • Conserved Gene Telomeric To Alpha Globin Cluster 2 3
  • GATOR Complex Protein NPRL3 3 4
  • -14 Gene Protein 3 4
  • C16orf35 3 4
  • HS-40 2 3
  • RMD11 2 3
  • NPR3 2 3
  • Nitrogen Permease Regulator-Like 3 (S. Cerevisiae) 2
  • Nitrogen Permease Regulator 3-Like Protein 4
  • Chromosome 16 Open Reading Frame 35 2
  • NPR3-Like, GATOR1 Complex Subunit 2
  • Protein CGTHBA 4
  • FFEVF3 3
  • NPRL3 5

External Ids for NPRL3 Gene

Previous HGNC Symbols for NPRL3 Gene

  • C16orf35

Previous GeneCards Identifiers for NPRL3 Gene

  • GC16M000134
  • GC16M000054

Summaries for NPRL3 Gene

Entrez Gene Summary for NPRL3 Gene

  • The function of the encoded protein is not known. [provided by RefSeq, Aug 2011]

GeneCards Summary for NPRL3 Gene

NPRL3 (NPR3 Like, GATOR1 Complex Subunit) is a Protein Coding gene. Diseases associated with NPRL3 include Epilepsy, Familial Focal, With Variable Foci 3 and Epilepsy, Familial Focal, With Variable Foci 1. Among its related pathways are mTOR signaling pathway (KEGG). Gene Ontology (GO) annotations related to this gene include GTPase activator activity.

UniProtKB/Swiss-Prot Summary for NPRL3 Gene

  • As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the TORC1 pathway. The GATOR1 complex strongly increases GTP hydrolysis by RRAGA and RRAGB within RRAGC-containing heterodimers, thereby deactivating RRAGs, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling. The GATOR1 complex is negatively regulated by GATOR2 the other GATOR subcomplex in this amino acid-sensing branch of the TORC1 pathway.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NPRL3 Gene

Genomics for NPRL3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NPRL3 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NPRL3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NPRL3

Genomic Locations for NPRL3 Gene

Genomic Locations for NPRL3 Gene
chr16:84,271-138,860
(GRCh38/hg38)
Size:
54,590 bases
Orientation:
Minus strand
chr16:134,273-188,859
(GRCh37/hg19)
Size:
54,587 bases
Orientation:
Minus strand

Genomic View for NPRL3 Gene

Genes around NPRL3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NPRL3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NPRL3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NPRL3 Gene

Proteins for NPRL3 Gene

  • Protein details for NPRL3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q12980-NPRL3_HUMAN
    Recommended name:
    GATOR complex protein NPRL3
    Protein Accession:
    Q12980
    Secondary Accessions:
    • D3DU40
    • Q1W6H0
    • Q4TT56
    • Q92469

    Protein attributes for NPRL3 Gene

    Size:
    569 amino acids
    Molecular mass:
    63605 Da
    Quaternary structure:
    • Forms a heterodimer with NPRL2. Within the GATOR complex, component of the GATOR1 subcomplex, made of DEPDC5, NPRL2 and NPRL3. GATOR1 mediates the strong interaction of the GATOR complex with RRAGA/RRAGC and RRAGB/RRAGC heterodimers.

    Three dimensional structures from OCA and Proteopedia for NPRL3 Gene

neXtProt entry for NPRL3 Gene

Post-translational modifications for NPRL3 Gene

  • Glycosylation at Asn465
  • Ubiquitination at Lys253 and Lys546
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • NPRL3_HUMAN (2060)

No data available for DME Specific Peptides for NPRL3 Gene

Domains & Families for NPRL3 Gene

Gene Families for NPRL3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for NPRL3 Gene

InterPro:
Blocks:
  • Protein of unknown function UPF0171
ProtoNet:

Suggested Antigen Peptide Sequences for NPRL3 Gene

GenScript: Design optimal peptide antigens:
  • Protein CGTHBA (NPRL3_HUMAN)
  • Chromosome 16 open reading frame 35 (Q4TT55_HUMAN)
  • cDNA FLJ33398 fis, clone BRACE2009558, highly similar to CGTHBA protein (Q9BTE2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q12980

UniProtKB/Swiss-Prot:

NPRL3_HUMAN :
  • Belongs to the NPR3 family.
Family:
  • Belongs to the NPR3 family.
genes like me logo Genes that share domains with NPRL3: view

Function for NPRL3 Gene

Molecular function for NPRL3 Gene

UniProtKB/Swiss-Prot Function:
As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the TORC1 pathway. The GATOR1 complex strongly increases GTP hydrolysis by RRAGA and RRAGB within RRAGC-containing heterodimers, thereby deactivating RRAGs, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling. The GATOR1 complex is negatively regulated by GATOR2 the other GATOR subcomplex in this amino acid-sensing branch of the TORC1 pathway.

Phenotypes From GWAS Catalog for NPRL3 Gene

Gene Ontology (GO) - Molecular Function for NPRL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005096 contributes_to GTPase activator activity IDA 23723238
GO:0005515 protein binding IPI 19521502
genes like me logo Genes that share ontologies with NPRL3: view
genes like me logo Genes that share phenotypes with NPRL3: view

Human Phenotype Ontology for NPRL3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for NPRL3 Gene

MGI Knock Outs for NPRL3:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NPRL3

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for NPRL3 Gene

Localization for NPRL3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NPRL3 Gene

Lysosome membrane. Note=Localization to lysosomes is amino acid-independent. {ECO:0000269 PubMed:28199306}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NPRL3 gene
Compartment Confidence
lysosome 5
mitochondrion 3
cytosol 3
extracellular 2
nucleus 2
endosome 2
plasma membrane 1
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for NPRL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005764 lysosome IEA --
GO:0005765 lysosomal membrane IEA,IDA 28199306
GO:0016020 membrane IEA --
GO:1990130 GATOR1 complex IDA 23723238
genes like me logo Genes that share ontologies with NPRL3: view

Pathways & Interactions for NPRL3 Gene

PathCards logo

SuperPathways for NPRL3 Gene

SuperPathway Contained pathways
1 mTOR signaling pathway (KEGG)
genes like me logo Genes that share pathways with NPRL3: view

Pathways by source for NPRL3 Gene

1 KEGG pathway for NPRL3 Gene

Gene Ontology (GO) - Biological Process for NPRL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003281 ventricular septum development IEA --
GO:0032007 negative regulation of TOR signaling IMP 23723238
GO:0034198 cellular response to amino acid starvation IMP 23723238
GO:0035909 aorta morphogenesis IEA --
GO:0038202 TORC1 signaling IBA 21873635
genes like me logo Genes that share ontologies with NPRL3: view

No data available for SIGNOR curated interactions for NPRL3 Gene

Drugs & Compounds for NPRL3 Gene

No Compound Related Data Available

Transcripts for NPRL3 Gene

mRNA/cDNA for NPRL3 Gene

6 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
14 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NPRL3

Alternative Splicing Database (ASD) splice patterns (SP) for NPRL3 Gene

No ASD Table

Relevant External Links for NPRL3 Gene

GeneLoc Exon Structure for
NPRL3

Expression for NPRL3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NPRL3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NPRL3 Gene

This gene is overexpressed in Whole Blood (x7.2).

Protein differential expression in normal tissues from HIPED for NPRL3 Gene

This gene is overexpressed in Bone marrow mesenchymal stem cell (68.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NPRL3 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NPRL3

SOURCE GeneReport for Unigene cluster for NPRL3 Gene:

Hs.19699

mRNA Expression by UniProt/SwissProt for NPRL3 Gene:

Q12980-NPRL3_HUMAN
Tissue specificity: Widely expressed. Expressed in the frontal lobe cortex as well as in the temporal, parietal, and occipital lobes (PubMed:27173016, PubMed:26505888).

Evidence on tissue expression from TISSUES for NPRL3 Gene

  • Liver(4.4)
  • Nervous system(3.6)
  • Lung(3)
  • Blood(2.8)
  • Eye(2.7)
  • Skin(2.4)
  • Muscle(2.3)
  • Kidney(2.3)
  • Bone marrow(2.2)
  • Heart(2)
genes like me logo Genes that share expression patterns with NPRL3: view

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for NPRL3 Gene

Orthologs for NPRL3 Gene

This gene was present in the common ancestor of animals.

Orthologs for NPRL3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NPRL3 30 31
  • 99.51 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia NPRL3 30 31
  • 90.93 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia NPRL3 30 31
  • 89.93 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia NPRL3 31
  • 89 (a)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Nprl3 30
  • 88.89 (n)
Mouse
(Mus musculus)
Mammalia Nprl3 30 17 31
  • 88.83 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia NPRL3 31
  • 70 (a)
OneToOne
Chicken
(Gallus gallus)
Aves CGTHBA 31
  • 86 (a)
OneToMany
NPRL3 30
  • 78.64 (n)
-- 31
  • 74 (a)
OneToMany
Lizard
(Anolis carolinensis)
Reptilia NPRL3 31
  • 85 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia nprl3 30
  • 72.12 (n)
Str.18308 30
African clawed frog
(Xenopus laevis)
Amphibia MGC68624 30
Zebrafish
(Danio rerio)
Actinopterygii nprl3 30 31
  • 73.96 (n)
OneToOne
wufb68d06 30
Fruit Fly
(Drosophila melanogaster)
Insecta CG8783 30 31
  • 51.08 (n)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea nprl-3 30 31
  • 39.66 (n)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 42 (a)
OneToOne
Species where no ortholog for NPRL3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for NPRL3 Gene

ENSEMBL:
Gene Tree for NPRL3 (if available)
TreeFam:
Gene Tree for NPRL3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NPRL3: view image

Paralogs for NPRL3 Gene

(1) SIMAP similar genes for NPRL3 Gene using alignment to 8 proteins:

  • NPRL3_HUMAN
  • A8MVF6_HUMAN
  • F8WBJ1_HUMAN
  • F8WCB2_HUMAN
  • F8WDA5_HUMAN
  • F8WE46_HUMAN
  • F8WEK2_HUMAN
  • F8WEK7_HUMAN
genes like me logo Genes that share paralogs with NPRL3: view

No data available for Paralogs for NPRL3 Gene

Variants for NPRL3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NPRL3 Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
637995 Likely Pathogenic: Epilepsy, familial focal, with variable foci 3 112,700(-) C/A NONSENSE,FIVE_PRIME_UTR_VARIANT
640170 Uncertain Significance: Epilepsy, familial focal, with variable foci 3 89,863(-) G/A MISSENSE_VARIANT
640217 Uncertain Significance: Epilepsy, familial focal, with variable foci 3 130,582(-) C/G MISSENSE_VARIANT,FIVE_PRIME_UTR_VARIANT
640488 Uncertain Significance: Epilepsy, familial focal, with variable foci 3 119,151(-) G/A MISSENSE_VARIANT,INTRON_VARIANT
643202 Uncertain Significance: Epilepsy, familial focal, with variable foci 3 88,840(-) C/T MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for NPRL3 Gene

Structural Variations from Database of Genomic Variants (DGV) for NPRL3 Gene

Variant ID Type Subtype PubMed ID
dgv2689n100 CNV gain 25217958
dgv2690n100 CNV gain 25217958
esv1304431 CNV insertion 17803354
esv2422427 CNV duplication 17116639
esv2657149 CNV deletion 23128226
esv2760065 CNV gain 17122850
esv2760406 CNV gain+loss 21179565
esv32706 CNV loss 17666407
esv3552956 CNV deletion 23714750
esv3637536 CNV loss 21293372
esv3637537 CNV gain 21293372
esv3637539 CNV loss 21293372
esv3637540 CNV gain 21293372
nsv1037664 CNV gain 25217958
nsv1044142 CNV gain 25217958
nsv1045829 CNV gain 25217958
nsv1050893 CNV gain 25217958
nsv1070306 CNV deletion 25765185
nsv1129572 CNV tandem duplication 24896259
nsv1132870 CNV insertion 24896259
nsv1697 CNV insertion 18451855
nsv518291 CNV loss 19592680
nsv570924 CNV loss 21841781
nsv9317 CNV gain 18304495
nsv958218 CNV deletion 24416366

Variation tolerance for NPRL3 Gene

Gene Damage Index Score: 2.86; 48.28% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NPRL3 Gene

Human Gene Mutation Database (HGMD)
NPRL3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NPRL3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NPRL3 Gene

Disorders for NPRL3 Gene

MalaCards: The human disease database

(16) MalaCards diseases for NPRL3 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
epilepsy, familial focal, with variable foci 3
  • ffevf3
epilepsy, familial focal, with variable foci 1
  • ffevf1
epilepsy
  • epilepsy syndrome
focal epilepsy
  • localisation-related epilepsy
corneal dystrophy, fleck
  • cfd
- elite association - COSMIC cancer census association via MalaCards
Search NPRL3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

NPRL3_HUMAN
  • Note=Inactivating mutations and truncating deletions in the genes encoding GATOR1 proteins are detected in glioblastoma and ovarian tumors and are associated with loss of heterozygosity events. Inactivation of GATOR1 proteins promotes constitutive localization of mTORC1 to the lysosomal membrane and blocks mTORC1 inactivation following amino acid withdrawal (PubMed:23723238). {ECO:0000269 PubMed:23723238}.
  • Epilepsy, familial focal, with variable foci 3 (FFEVF3) [MIM:617118]: An autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions, including the temporal, frontal, parietal, and occipital lobes. Seizure types commonly include temporal lobe epilepsy, frontal lobe epilepsy, and nocturnal frontal lobe epilepsy. Some patients may have intellectual disability or autism spectrum disorders. Seizure onset usually occurs in the first or second decades, although later onset has been reported, and there is phenotypic variability within families. A subset of patients have structural brain abnormalities. Penetrance of the disorder is incomplete. {ECO:0000269 PubMed:26285051, ECO:0000269 PubMed:26505888, ECO:0000269 PubMed:27173016}. Note=The disease is caused by mutations affecting the gene represented in this entry.
genes like me logo Genes that share disorders with NPRL3: view

No data available for Genatlas for NPRL3 Gene

Publications for NPRL3 Gene

  1. Conservation of position and sequence of a novel, widely expressed gene containing the major human alpha-globin regulatory element. (PMID: 8575760) Vyas P … Higgs DR (Genomics 1995) 2 3 4
  2. KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1. (PMID: 28199306) Wolfson RL … Sabatini DM (Nature 2017) 3 4
  3. Mutations in the mammalian target of rapamycin pathway regulators NPRL2 and NPRL3 cause focal epilepsy. (PMID: 26505888) Ricos MG … Dibbens LM (Annals of neurology 2016) 3 4
  4. Involvement of GATOR complex genes in familial focal epilepsies and focal cortical dysplasia. (PMID: 27173016) Weckhuysen S … Baulac S (Epilepsia 2016) 3 4
  5. Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3. (PMID: 26285051) Sim JC … Leventer RJ (Annals of neurology 2016) 3 4

Products for NPRL3 Gene

Sources for NPRL3 Gene