GeneBe

NPRL3

NPR3 like, GATOR1 complex subunit, the group of GATOR1 subcomplex

Basic information

Region (hg38): 16:84271-138677

Previous symbols: [ "C16orf35" ]

Links

ENSG00000103148 ∙ NCBI:8131 ∙ OMIM:600928 ∙ HGNC:14124 ∙ Uniprot:Q12980 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • familial focal epilepsy with variable foci (Supportive), mode of inheritance: AD
  • focal epilepsy (Definitive), mode of inheritance: AD
  • epilepsy, familial focal, with variable foci 3 (Moderate), mode of inheritance: AD
  • epilepsy, familial focal, with variable foci 3 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Epilepsy, familial focal, with variable foci 3ADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic26285051; 26505888; 27173016

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NPRL3 gene.

  • Epilepsy, familial focal, with variable foci 3 (61 variants)
  • not provided (10 variants)
  • Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NPRL3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
12
clinvar
137
clinvar
4
clinvar
 153
missense
1
clinvar
288
clinvar
6
clinvar
4
clinvar
 299
nonsense
24
clinvar
6
clinvar
1
clinvar
 31
start loss
0
frameshift
39
clinvar
7
clinvar
6
clinvar
1
clinvar
1
clinvar
 54
inframe indel
13
clinvar
 13
splice donor/acceptor (+/-2bp)
4
clinvar
20
clinvar
2
clinvar
1
clinvar
 27
splice region
3
39
20
2
 64
non coding
32
clinvar
121
clinvar
55
clinvar
 208
Total 68 33 354 266 64

Variants in NPRL3

This is a list of pathogenic ClinVar variants found in the NPRL3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
16-85401-G-C not specified Uncertain significance (Apr 05, 2023)2533028
16-85401-G-T not specified Uncertain significance (Apr 19, 2024)3295676
16-85481-C-G not specified Uncertain significance (Feb 21, 2024)3201780
16-85493-G-A not specified Uncertain significance (Sep 17, 2021)2251275
16-85508-A-G not specified Uncertain significance (Mar 20, 2023)2507572
16-85517-G-A not specified Uncertain significance (Feb 09, 2023)2482627
16-85536-C-G not specified Uncertain significance (May 31, 2023)2553692
16-85583-G-A not specified Uncertain significance (Dec 31, 2023)3201785
16-85592-C-A not specified Uncertain significance (Dec 20, 2023)3201788
16-85609-G-A not specified Uncertain significance (Apr 09, 2024)3251408
16-85609-G-T not specified Uncertain significance (Nov 27, 2023)3201791
16-85616-C-T not specified Uncertain significance (Sep 22, 2022)2325128
16-85659-C-T not specified Uncertain significance (Oct 25, 2022)2319002
16-85661-C-T not specified Uncertain significance (Jul 06, 2021)2400860
16-85673-G-A not specified Uncertain significance (Feb 01, 2023)2464870
16-85694-C-T not specified Uncertain significance (Jun 18, 2021)2233601
16-85701-C-T not specified Uncertain significance (May 01, 2022)2400630
16-85707-G-A not specified Uncertain significance (Sep 17, 2021)2375288
16-85733-G-A not specified Uncertain significance (Nov 08, 2022)2408517
16-85742-G-A not specified Uncertain significance (Dec 20, 2023)3201829
16-86520-C-T Likely benign (Jul 21, 2018)1195638
16-86630-C-T Likely benign (Aug 03, 2018)1187214
16-86637-A-C Benign (Jul 26, 2018)1240682
16-86662-G-A Likely benign (Aug 30, 2018)1211903
16-86667-C-G Benign (Nov 02, 2020)1265007

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
NPRL3protein_codingprotein_codingENST00000399953 1454587
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.1900.81072912396971247050.924
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.842453400.7200.00002163661
Missense in Polyphen6593.9760.691661084
Synonymous-0.1521491471.020.000009981131
Loss of Function3.42624.10.2490.00000118281

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American2.001.89
Ashkenazi Jewish1.000.928
East Asian1.000.955
Finnish1.000.934
European (Non-Finnish)1.000.913
Middle Eastern1.000.955
South Asian1.000.956
Other1.000.917

dbNSFP

Source: dbNSFP

Function
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. {ECO:0000269|PubMed:23723238}.;
Disease
DISEASE: 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.;
Pathway
mTOR signaling pathway - Homo sapiens (human) (Consensus)

Recessive Scores

pRec
0.147

Haploinsufficiency Scores

pHI
0.164
hipred
N
hipred_score
0.481
ghis
0.422

Essentials

essential_gene_CRISPR
essential_gene_CRISPR2
N
essential_gene_gene_trap
gene_indispensability_pred
E
gene_indispensability_score
0.731

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Nprl3
Phenotype
immune system phenotype; digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; liver/biliary system phenotype; homeostasis/metabolism phenotype; muscle phenotype; craniofacial phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype;

Gene ontology

Biological process
ventricular septum development;negative regulation of TOR signaling;cellular response to amino acid starvation;aorta morphogenesis;TORC1 signaling;positive regulation of GTPase activity;cardiac muscle tissue development;roof of mouth development;regulation of autophagosome assembly
Cellular component
lysosomal membrane;GATOR1 complex
Molecular function
GTPase activator activity;protein binding