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    NPRL3 NPR3 like, GATOR1 complex subunit [ Homo sapiens (human) ]

    Gene ID: 8131, updated on 2-May-2024

    Summary

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    Official Symbol
    NPRL3provided by HGNC
    Official Full Name
    NPR3 like, GATOR1 complex subunitprovided by HGNC
    Primary source
    HGNC:HGNC:14124
    See related
    Ensembl:ENSG00000103148 MIM:600928; AllianceGenome:HGNC:14124
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MARE; NPR3; HS-40; RMD11; CGTHBA; FFEVF3; C16orf35
    Summary
    Contributes to GTPase activator activity. Involved in cellular response to amino acid starvation and negative regulation of TOR signaling. Located in lysosomal membrane. Part of GATOR1 complex. Implicated in focal epilepsy. [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Ubiquitous expression in testis (RPKM 11.3), ovary (RPKM 10.7) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    16p13.3
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (85386..138673, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (78987..132241, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (135385..188672, complement)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6897 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6898 Neighboring gene small nuclear ribonucleoprotein U11/U12 subunit 25 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10199 Neighboring gene rhomboid 5 homolog 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:120389-121206 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:122199-122382 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6899 Neighboring gene uncharacterized LOC124903617 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:122843-123660 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:123661-124478 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:124479-125296 Neighboring gene Sharpr-MPRA regulatory region 13767 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:133607-134462 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6901 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10200 Neighboring gene N-methylpurine DNA glycosylase Neighboring gene alpha-globin locus control region Neighboring gene uncharacterized LOC107983982 Neighboring gene hemoglobin subunit zeta

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. The clinical features of familial focal epilepsy with variable foci and NPRL3 gene variant. Wang Y, et al. PLoS One, 2023. PMID 37099548, Free PMC Article
    2. A human minisatellite hosts an alternative transcription start site for NPRL3 driving its expression in a repeat number-dependent manner. Bertuzzi M, et al. Hum Mutat, 2020 Apr. PMID 31898848
    3. Inclusion of hemimegalencephaly into the phenotypic spectrum of NPRL3 pathogenic variants in familial focal epilepsy with variable foci. Canavati C, et al. Epilepsia, 2019 Jun. PMID 31111464
    4. Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3. Sim JC, et al. Ann Neurol, 2016 Jan. PMID 26285051
    5. Hemimegalencephaly and intractable seizures associated with the NPRL3 gene variant in a newborn: A case report. Chandrasekar I, et al. Am J Med Genet A, 2021 Jul. PMID 33749980

    See all (45) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Phenotypic and genotypic characterization of NPRL3-related epilepsy: Two case reports and literature review.
      Title: Phenotypic and genotypic characterization of NPRL3-related epilepsy: Two case reports and literature review.
    2. Refining the electroclinical spectrum of NPRL3-related epilepsy: A novel multiplex family and literature review.
      Title: Refining the electroclinical spectrum of NPRL3-related epilepsy: A novel multiplex family and literature review.
    3. Seizure features and outcomes in 50 children with GATOR1 variants: A retrospective study, more favorable for epilepsy surgery.
      Title: Seizure features and outcomes in 50 children with GATOR1 variants: A retrospective study, more favorable for epilepsy surgery.
    4. Functional characterization of novel NPRL3 mutations identified in three families with focal epilepsy.
      Title: Functional characterization of novel NPRL3 mutations identified in three families with focal epilepsy.
    5. The clinical features of familial focal epilepsy with variable foci and NPRL3 gene variant.
      Title: The clinical features of familial focal epilepsy with variable foci and NPRL3 gene variant.
    6. Hemimegalencephaly and intractable seizures associated with the NPRL3 gene variant in a newborn: A case report.
      Title: Hemimegalencephaly and intractable seizures associated with the NPRL3 gene variant in a newborn: A case report.
    7. A human minisatellite hosts an alternative transcription start site for NPRL3 driving its expression in a repeat number-dependent manner.
      Title: A human minisatellite hosts an alternative transcription start site for NPRL3 driving its expression in a repeat number-dependent manner.
    8. Diagnostic exome sequencing in non-acquired focal epilepsies highlights a major role of GATOR1 complex genes.
      Title: Diagnostic exome sequencing in non-acquired focal epilepsies highlights a major role of GATOR1 complex genes.
    9. GATOR1-related focal cortical dysplasia in epilepsy surgery patients and their families: A possible gradient in severity?
      Title: GATOR1-related focal cortical dysplasia in epilepsy surgery patients and their families: A possible gradient in severity?
    10. Our results implicate the association of NPRL3 with hemimegalencephaly, expanding the phenotypic spectrum of NPRL3 in FFEVF and underlining that partial deletions are part of the genotypic spectrum of NPRL3 variants
      Title: Inclusion of hemimegalencephaly into the phenotypic spectrum of NPRL3 pathogenic variants in familial focal epilepsy with variable foci.
    Submit: New GeneRIF Correction See all GeneRIFs (17)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Epilepsy, familial focal, with variable foci 3
    MedGen: C4310708 OMIM: 617118 GeneReviews: Not available
    		Compare labs

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2023-12-12)

    ClinGen Genome Curation PagePubMed
    Triplosensitivity

    No evidence available (Last evaluated 2023-12-12)

    ClinGen Genome Curation Page

    EBI GWAS Catalog

    Description
    Genetic determinants of haemolysis in sickle cell anaemia.
    EBI GWAS Catalog
    Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network.
    EBI GWAS Catalog
    GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children.
    EBI GWAS Catalog
    Seventy-five genetic loci influencing the human red blood cell.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables GTPase activator activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in TORC1 signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in aorta morphogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cardiac muscle tissue development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to amino acid starvation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cellular response to amino acid starvation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to amino acid starvation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of TORC1 signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of TORC1 signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of TORC1 signaling NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of autophagy IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in roof of mouth development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in ventricular septum development IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    part_of GATOR1 complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of GATOR1 complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of GATOR1 complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    is_active_in lysosomal membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in lysosomal membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in lysosomal membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    GATOR1 complex protein NPRL3
    Names
    -14 gene protein
    GATOR complex protein NPRL3
    alpha-globin regulatory element-containing gene protein
    conserved gene telomeric to alpha globin cluster

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029669.2 RefSeqGene

      Range
      4975..58287
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001039476.3 → NP_001034565.1  GATOR1 complex protein NPRL3 isoform 2

      See identical proteins and their annotated locations for NP_001034565.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.
      Source sequence(s)
      AK090717, Z69666, Z69720
      UniProtKB/TrEMBL
      Q9BTE2
      Conserved Domains (1) summary
      cl24021
      Location:15 → 237
      NPR3; Nitrogen Permease regulator of amino acid transport activity 3

    2. NM_001077350.3 → NP_001070818.1  GATOR1 complex protein NPRL3 isoform 1

      See identical proteins and their annotated locations for NP_001070818.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AK090717, DA258664, Z69666, Z69720
      Consensus CDS
      CCDS73795.1
      UniProtKB/Swiss-Prot
      D3DU40, Q12980, Q1W6H0, Q4TT56, Q92469
      UniProtKB/TrEMBL
      Q4TT55
      Related
      ENSP00000478273.1, ENST00000611875.5
      Conserved Domains (1) summary
      cl24021
      Location:64 → 416
      NPR3; Nitrogen Permease regulator of amino acid transport activity 3

    3. NM_001243247.2 → NP_001230176.1  GATOR1 complex protein NPRL3 isoform 3

      See identical proteins and their annotated locations for NP_001230176.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1.
      Source sequence(s)
      AK294228, DA075508, DC384076, Z69720
      UniProtKB/TrEMBL
      B7Z220
      Conserved Domains (1) summary
      cl24021
      Location:1 → 338
      NPR3; Nitrogen Permease regulator of amino acid transport activity 3

    4. NM_001243248.2 → NP_001230177.1  GATOR1 complex protein NPRL3 isoform 4

      See identical proteins and their annotated locations for NP_001230177.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (4) lacks an alternate internal segment compared to isoform 1. Variants 4 and 5 both encode the same isoform (4).
      Source sequence(s)
      AK300736, Z69666, Z69720
      Consensus CDS
      CCDS73794.1
      UniProtKB/TrEMBL
      B7Z6Q0, Q4TT55
      Conserved Domains (1) summary
      cl24021
      Location:64 → 391
      NPR3; Nitrogen Permease regulator of amino acid transport activity 3

    5. NM_001243249.2 → NP_001230178.1  GATOR1 complex protein NPRL3 isoform 4

      See identical proteins and their annotated locations for NP_001230178.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (4) lacks an alternate internal segment compared to isoform 1. Variants 4 and 5 both encode the same isoform (4).
      Source sequence(s)
      BC020392, Z69666, Z69720
      Consensus CDS
      CCDS73794.1
      UniProtKB/TrEMBL
      B7Z6Q0, Q4TT55
      Related
      ENSP00000382834.4, ENST00000399953.7
      Conserved Domains (1) summary
      cl24021
      Location:64 → 391
      NPR3; Nitrogen Permease regulator of amino acid transport activity 3

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      85386..138673 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      78987..132241 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_012075.1: Suppressed sequence

      Description
      NM_012075.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q12980.1 GenPept UniProtKB/Swiss-Prot:Q12980

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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