This gene encodes a putative member of the class II family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. This protein is encoded by the nuclear genome but is likely to be imported to the mitochondrion where it is thought to catalyze the ligation of asparagine to tRNA molecules. Mutatio... See more...

Aliases for NARS2 Gene

Aliases for NARS2 Gene

  • Asparaginyl-TRNA Synthetase 2, Mitochondrial 2 3 5
  • Asparaginyl-TRNA Synthetase 2, Mitochondrial (Putative) 2 3
  • Asparagine TRNA Ligase 2, Mitochondrial (Putative) 2 3
  • Probable Asparagine--TRNA Ligase, Mitochondrial 3 4
  • Deafness, Autosomal Recessive 94 2 3
  • EC 6.1.1.22 4 50
  • AsnRS 3 4
  • SLM5 2 3
  • Probable Asparaginyl-TRNA Synthetase, Mitochondrial 3
  • Asparaginyl-TRNA Synthetase 4
  • FLJ23441 2
  • EC 6.1.1 50
  • DFNB94 3
  • NARS2 5

External Ids for NARS2 Gene

Previous HGNC Symbols for NARS2 Gene

  • DFNB94

Previous GeneCards Identifiers for NARS2 Gene

  • GC11M077825
  • GC11M078147
  • GC11M074444

Summaries for NARS2 Gene

Entrez Gene Summary for NARS2 Gene

  • This gene encodes a putative member of the class II family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. This protein is encoded by the nuclear genome but is likely to be imported to the mitochondrion where it is thought to catalyze the ligation of asparagine to tRNA molecules. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency 24 (COXPD24). [provided by RefSeq, Mar 2015]

GeneCards Summary for NARS2 Gene

NARS2 (Asparaginyl-TRNA Synthetase 2, Mitochondrial) is a Protein Coding gene. Diseases associated with NARS2 include Combined Oxidative Phosphorylation Deficiency 24 and Deafness, Autosomal Recessive 94. Among its related pathways are tRNA Aminoacylation and Ectoderm Differentiation. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and aminoacyl-tRNA ligase activity. An important paralog of this gene is NARS1.

No data available for CIViC Summary , UniProtKB/Swiss-Prot Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NARS2 Gene

Genomics for NARS2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NARS2 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 NARS2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NARS2

Top Transcription factor binding sites by QIAGEN in the NARS2 gene promoter:
  • AP-4
  • Evi-1
  • HNF-4alpha1
  • HNF-4alpha2
  • MZF-1
  • NF-AT
  • NF-AT1
  • NF-AT2
  • NF-AT3
  • NF-AT4

Genomic Locations for NARS2 Gene

Latest Assembly
chr11:78,435,968-78,574,874
(GRCh38/hg38)
Size:
138,907 bases
Orientation:
Minus strand

Previous Assembly
chr11:78,147,014-78,285,909
(GRCh37/hg19 by Entrez Gene)
Size:
138,896 bases
Orientation:
Minus strand

chr11:78,147,007-78,285,919
(GRCh37/hg19 by Ensembl)
Size:
138,913 bases
Orientation:
Minus strand

Genomic View for NARS2 Gene

Genes around NARS2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NARS2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NARS2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NARS2 Gene

Proteins for NARS2 Gene

  • Protein details for NARS2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96I59-SYNM_HUMAN
    Recommended name:
    Probable asparagine--tRNA ligase, mitochondrial
    Protein Accession:
    Q96I59
    Secondary Accessions:
    • G3V178

    Protein attributes for NARS2 Gene

    Size:
    477 amino acids
    Molecular mass:
    54090 Da
    Quaternary structure:
    • Homodimer.

    Alternative splice isoforms for NARS2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NARS2 Gene

Selected DME Specific Peptides for NARS2 Gene

Q96I59:
  • LTVSGQL
  • TFGPTFRAE
  • PIITSND
  • YTEAVEIL
  • WYLDLRR
  • PTFRAENS

Post-translational modifications for NARS2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for NARS2 Gene

Gene Families for NARS2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for NARS2 Gene

InterPro:
Blocks:
  • Aspartyl-tRNA synthetase signature
  • tRNA synthetase, class II (D, K and N)
  • OB-fold nucleic acid binding domain

Suggested Antigen Peptide Sequences for NARS2 Gene

GenScript: Design optimal peptide antigens:
  • Asparagine--tRNA ligase (SYNM_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96I59

UniProtKB/Swiss-Prot:

SYNM_HUMAN :
  • Belongs to the class-II aminoacyl-tRNA synthetase family.
Family:
  • Belongs to the class-II aminoacyl-tRNA synthetase family.
genes like me logo Genes that share domains with NARS2: view

Function for NARS2 Gene

Molecular function for NARS2 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-asparagine + tRNA(Asn) = AMP + diphosphate + H(+) + L-asparaginyl-tRNA(Asn); Xref=Rhea:RHEA:11180, Rhea:RHEA-COMP:9659, Rhea:RHEA-COMP:9674, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58048, ChEBI:CHEBI:78442, ChEBI:CHEBI:78515, ChEBI:CHEBI:456215; EC=6.1.1.22;.

Enzyme Numbers (IUBMB) for NARS2 Gene

Phenotypes From GWAS Catalog for NARS2 Gene

Gene Ontology (GO) - Molecular Function for NARS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0003676 nucleic acid binding IEA --
GO:0004812 aminoacyl-tRNA ligase activity IEA --
GO:0004816 asparagine-tRNA ligase activity ISS --
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with NARS2: view
genes like me logo Genes that share phenotypes with NARS2: view

Human Phenotype Ontology for NARS2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for research

  • Taconic Biosciences Mouse Models for NARS2

miRNA for NARS2 Gene

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NARS2

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for NARS2 Gene

Localization for NARS2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NARS2 Gene

Mitochondrion matrix. Mitochondrion.

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 NARS2 gene
Compartment Confidence
mitochondrion 5
cytosol 5
nucleus 4
plasma membrane 1
extracellular 1
cytoskeleton 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Mitochondria (3)
  • Cytosol (1)
  • Nucleoplasm (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NARS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm IDA --
GO:0005739 mitochondrion ISS --
GO:0005759 mitochondrial matrix IEA --
GO:0005829 cytosol IDA --
genes like me logo Genes that share ontologies with NARS2: view

Pathways & Interactions for NARS2 Gene

genes like me logo Genes that share pathways with NARS2: view

Pathways by source for NARS2 Gene

1 BioSystems pathway for NARS2 Gene
1 KEGG pathway for NARS2 Gene

Gene Ontology (GO) - Biological Process for NARS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006412 translation IEA --
GO:0006418 tRNA aminoacylation for protein translation IEA --
GO:0006421 asparaginyl-tRNA aminoacylation ISS --
genes like me logo Genes that share ontologies with NARS2: view

No data available for SIGNOR curated interactions for NARS2 Gene

Drugs & Compounds for NARS2 Gene

(4) Drugs for NARS2 Gene - From: DrugBank and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Asparagine Approved, Investigational Nutra Target 40
Adenosine monophosphate Approved, Investigational Nutra 0
Phosphate Experimental Pharma 0
ATP Investigational Nutra 0

(1) Additional Compounds for NARS2 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
pyrophosphate
  • [(HO)2P(O)OP(O)(OH)2]
  • Acide diphosphorique
  • Diphosphorsaeure
  • H4P2O7
  • Pyrophosphoric acid
14000-31-8
genes like me logo Genes that share compounds with NARS2: view

Transcripts for NARS2 Gene

mRNA/cDNA for NARS2 Gene

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

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NARS2

Alternative Splicing Database (ASD) splice patterns (SP) for NARS2 Gene

No ASD Table

Relevant External Links for NARS2 Gene

GeneLoc Exon Structure for
NARS2

Expression for NARS2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NARS2 Gene

Protein differential expression in normal tissues from HIPED for NARS2 Gene

This gene is overexpressed in Adrenal (7.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NARS2 Gene



Protein tissue co-expression partners for NARS2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NARS2

SOURCE GeneReport for Unigene cluster for NARS2 Gene:

Hs.503389

Evidence on tissue expression from TISSUES for NARS2 Gene

  • Nervous system(4.5)
  • Liver(4.4)

Phenotype-based relationships between genes and organs from Gene ORGANizer for NARS2 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • nervous
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cranial nerve
  • face
  • head
  • skull
General:
  • peripheral nervous system
genes like me logo Genes that share expression patterns with NARS2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for NARS2 Gene

Orthologs for NARS2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for NARS2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NARS2 29 30
  • 99.51 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia NARS2 29
  • 89.66 (n)
Cow
(Bos Taurus)
Mammalia NARS2 29 30
  • 89.59 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Nars2 29 16 30
  • 85.19 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Nars2 29
  • 83.8 (n)
Oppossum
(Monodelphis domestica)
Mammalia NARS2 30
  • 77 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia NARS2 30
  • 61 (a)
OneToOne
Chicken
(Gallus gallus)
Aves NARS2 29 30
  • 72.76 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia NARS2 30
  • 71 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia nars2 29
  • 68.06 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.31151 29
Zebrafish
(Danio rerio)
Actinopterygii nars2 29 30
  • 65.71 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP001276 29
  • 50.66 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta CG6796 29 30
  • 49.3 (n)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea nars-2 30
  • 37 (a)
OneToOne
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes SLM5 29 30 32
  • 48.51 (n)
OneToOne
K. Lactis Yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0A11484g 29
  • 47.87 (n)
A. gosspyii yeast
(Eremothecium gossypii)
Saccharomycetes AGOS_AEL054C 29
  • 46.73 (n)
Thale Cress
(Arabidopsis thaliana)
eudicotyledons NS1 29
  • 54.88 (n)
Soybean
(Glycine max)
eudicotyledons Gma.3210 29
Rice
(Oryza sativa)
Liliopsida Os07g0485400 29
  • 54.95 (n)
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes slm5 29
  • 51.97 (n)
Bread mold
(Neurospora crassa)
Ascomycetes NCU06866 29
  • 48.43 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.2995 30
  • 41 (a)
OneToOne
Species where no ortholog for NARS2 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • 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 Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for NARS2 Gene

ENSEMBL:
Gene Tree for NARS2 (if available)
TreeFam:
Gene Tree for NARS2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NARS2: view image
Alliance of Genome Resources:
Additional Orthologs for NARS2

Paralogs for NARS2 Gene

Paralogs for NARS2 Gene

(3) SIMAP similar genes for NARS2 Gene using alignment to 5 proteins:

  • SYNM_HUMAN
  • E9PRK2_HUMAN
  • G3V178_HUMAN
  • H0YE96_HUMAN
  • H0YEL9_HUMAN
genes like me logo Genes that share paralogs with NARS2: view

Variants for NARS2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NARS2 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
1028840 Uncertain Significance: Combined oxidative phosphorylation deficiency 24 78,436,801(-) G/A
NM_024678.6(NARS2):c.1303C>T (p.Arg435Cys)
MISSENSE
1028841 Uncertain Significance: Combined oxidative phosphorylation deficiency 24 78,528,924(-) G/GGCT
NM_024678.6(NARS2):c.606_607insAGC (p.Leu203_Lys204insSer)
INFRAME_INSERTION,FIVE_PRIME_UTR
1029917 Uncertain Significance: Combined oxidative phosphorylation deficiency 24 78,478,659(-) T/C
NM_024678.6(NARS2):c.847A>G (p.Thr283Ala)
MISSENSE
1033638 Uncertain Significance: Combined oxidative phosphorylation deficiency 24 78,574,343(-) C/G
NM_024678.6(NARS2):c.141+5G>C
INTRON
1033639 Uncertain Significance: Combined oxidative phosphorylation deficiency 24 78,566,209(-) T/C
NM_024678.6(NARS2):c.436A>G (p.Arg146Gly)
MISSENSE_VARIANT,FIVE_PRIME_UTR

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for NARS2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for NARS2 Gene

Variant ID Type Subtype PubMed ID
dgv211e214 CNV gain 21293372
esv2662654 CNV deletion 23128226
esv3579755 CNV loss 25503493
esv3626901 CNV loss 21293372
esv3626904 CNV gain 21293372
esv3892027 CNV gain 25118596
nsv1147651 CNV insertion 26484159
nsv468642 CNV gain 19166990
nsv516040 CNV loss 19592680
nsv555454 CNV gain 21841781

Variation tolerance for NARS2 Gene

Residual Variation Intolerance Score: 45.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.40; 42.48% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NARS2 Gene

Human Gene Mutation Database (HGMD)
NARS2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NARS2
Leiden Open Variation Database (LOVD)
NARS2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NARS2 Gene

Disorders for NARS2 Gene

MalaCards: The human disease database

(11) MalaCards diseases for NARS2 Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search NARS2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SYNM_HUMAN
  • Combined oxidative phosphorylation deficiency 24 (COXPD24) [MIM:616239]: An autosomal recessive mitochondrial disorder with wide phenotypic variability. Some patients have a milder form affecting only skeletal muscle, whereas others may have a more severe disorder, reminiscent of Alpers syndrome. Alpers syndrome is a progressive neurodegenerative disorder that presents in infancy or early childhood and is characterized by diffuse degeneration of cerebral gray matter. {ECO:0000269 PubMed:25385316, ECO:0000269 PubMed:25629079, ECO:0000269 PubMed:25807530}. Note=The disease is caused by variants affecting the gene represented in this entry.
  • Deafness, autosomal recessive, 94 (DFNB94) [MIM:618434]: A form of non-syndromic, sensorineural deafness characterized by prelingual, profound, bilateral hearing impairment. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269 PubMed:25807530}. Note=The disease may be caused by variants affecting the gene represented in this entry.

Additional Disease Information for NARS2

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with NARS2: view

No data available for Genatlas for NARS2 Gene

Publications for NARS2 Gene

  1. Mutations of human NARS2, encoding the mitochondrial asparaginyl-tRNA synthetase, cause nonsyndromic deafness and Leigh syndrome. (PMID: 25807530) Simon M … Riazuddin S (PLoS genetics 2015) 2 3 4 72
  2. Two siblings with homozygous pathogenic splice-site variant in mitochondrial asparaginyl-tRNA synthetase (NARS2). (PMID: 25385316) Vanlander AV … Van Coster R (Human mutation 2015) 3 4 72
  3. Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS. (PMID: 15779907) Bonnefond L … Sissler M (Biochemistry 2005) 2 3 4
  4. Whole exome sequencing reveals mutations in NARS2 and PARS2, encoding the mitochondrial asparaginyl-tRNA synthetase and prolyl-tRNA synthetase, in patients with Alpers syndrome. (PMID: 25629079) Sofou K … Asin-Cayuela J (Molecular genetics & genomic medicine 2015) 3 4
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 40

Products for NARS2 Gene

Sources for NARS2 Gene