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    WARS2 tryptophanyl tRNA synthetase 2, mitochondrial [ Homo sapiens (human) ]

    Gene ID: 10352, updated on 5-Mar-2024

    Summary

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    Official Symbol
    WARS2provided by HGNC
    Official Full Name
    tryptophanyl tRNA synthetase 2, mitochondrialprovided by HGNC
    Primary source
    HGNC:HGNC:12730
    See related
    Ensembl:ENSG00000116874 MIM:604733; AllianceGenome:HGNC:12730
    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
    TrpRS; PKDYS3; NEMMLAS; mtTrpRS
    Summary
    Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Two forms of tryptophanyl-tRNA synthetase exist, a cytoplasmic form, named WARS, and a mitochondrial form, named WARS2. This gene encodes the mitochondrial tryptophanyl-tRNA synthetase. Two alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in kidney (RPKM 4.3), colon (RPKM 4.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    1p12
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (119031216..119140672, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (119044400..119154015, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (119573839..119683295, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene skeletal muscle cis-regulatory module in TBX15 intron Neighboring gene T-box transcription factor 15 Neighboring gene Sharpr-MPRA regulatory region 5383 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr1:119502746-119503360 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:119527836-119528513 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:119529833-119530366 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:119530367-119530899 Neighboring gene uncharacterized LOC105378933 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:119544270-119545093 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_115 Neighboring gene NANOG hESC enhancer GRCh37_chr1:119585151-119585652 Neighboring gene MPRA-validated peak395 silencer Neighboring gene WARS2 intronic transcript 1 Neighboring gene RBMX2 pseudogene 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1590 Neighboring gene RPS3A pseudogene 12 Neighboring gene WARS2 antisense RNA 1 Neighboring gene uncharacterized LOC107985192 Neighboring gene ribosomal protein L6 pseudogene 2

    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 Expanding Phenotypical Spectrum of WARS2-Related Disorder: Four Novel Cases with a Common Recurrent Variant. Pauly MG, et al. Genes (Basel), 2023 Mar 29. PMID 37107582, Free PMC Article
    2. A lead candidate functional single nucleotide polymorphism within the WARS2 gene associated with waist-hip-ratio does not alter RNA stability. Mušo M, et al. Biochim Biophys Acta Gene Regul Mech, 2020 Nov. PMID 33007465, Free PMC Article
    3. Biallelic mutations in mitochondrial tryptophanyl-tRNA synthetase cause Levodopa-responsive infantile-onset Parkinsonism. Burke EA, et al. Clin Genet, 2018 Mar. PMID 29120065, Free PMC Article
    4. An alternative conformation of human TrpRS suggests a role of zinc in activating non-enzymatic function. Xu X, et al. RNA Biol, 2018. PMID 28910573, Free PMC Article
    5. Biallelic variants in WARS2 encoding mitochondrial tryptophanyl-tRNA synthase in six individuals with mitochondrial encephalopathy. Wortmann SB, et al. Hum Mutat, 2017 Dec. PMID 28905505

    See all (39) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The Expanding Phenotypical Spectrum of WARS2-Related Disorder: Four Novel Cases with a Common Recurrent Variant.
      Title: The Expanding Phenotypical Spectrum of WARS2-Related Disorder: Four Novel Cases with a Common Recurrent Variant.
    2. Mini-TrpRS is essential for IFNgamma-induced monocyte-derived giant cell formation.
      Title: Mini-TrpRS is essential for IFNγ-induced monocyte-derived giant cell formation.
    3. A lead candidate functional single nucleotide polymorphism within the WARS2 gene associated with waist-hip-ratio does not alter RNA stability.
      Title: A lead candidate functional single nucleotide polymorphism within the WARS2 gene associated with waist-hip-ratio does not alter RNA stability.
    4. This case expands the phenotypic spectrum of WARS2 deficiency and emphasizes the importance of mitochondrial protein synthesis in the pathogenesis of Parkinsonism.
      Title: Biallelic mutations in mitochondrial tryptophanyl-tRNA synthetase cause Levodopa-responsive infantile-onset Parkinsonism.
    5. An alternative conformation of human TrpRS suggests a role of zinc in activating non-enzymatic function.
      Title: An alternative conformation of human TrpRS suggests a role of zinc in activating non-enzymatic function.
    6. The data demonstrate a pro-angiogenic function for Wars2 both within and outside the heart.
      Title: Wars2 is a determinant of angiogenesis.
    7. This confidently implicates that mutations in WARS2 cause mitochondrial disease with a broad spectrum of clinical presentation.
      Title: Biallelic variants in WARS2 encoding mitochondrial tryptophanyl-tRNA synthase in six individuals with mitochondrial encephalopathy.
    8. we found a compound heterozygous genotype of the mitochondrial tryptophanyl-tRNA synthetase (WARS2) gene, comprising a nonsense mutation (c.325delA, p.Ser109Alafs*15), which very likely entails nonsense-mediated mRNA decay and a missense mutation
      Title: Mutations of the aminoacyl-tRNA-synthetases SARS and WARS2 are implicated in the etiology of autosomal recessive intellectual disability.
    9. Here we substantially extend and consolidate the symptomatology of WARS2 by presenting a patient with severe infantile-onset leukoencephalopathy, profound intellectual disability, spastic quadriplegia, epilepsy, microcephaly, short stature, failure to thrive, cerebral atrophy, and periventricular white matter abnormalities
      Title: Deficiency of WARS2, encoding mitochondrial tryptophanyl tRNA synthetase, causes severe infantile onset leukoencephalopathy.
    10. first genome-wide scan for selection in Inuit from Greenland. A region, with a deeply divergent haplotype that is closely related to the sequence in the Denisovan genome contains two genes, WARS2 and TBX15. our study suggests a complex multi-factorial regulation of TBX15 and WARS2. We show that the introgressed region is associated with regional changes in methylation and expression levels
      Title: Archaic Adaptive Introgression in TBX15/WARS2.
    Submit: New GeneRIF Correction See all GeneRIFs (14)

    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

    EBI GWAS Catalog

    Description
    Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.
    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 ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables tryptophan-tRNA ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables tryptophan-tRNA ligase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables tryptophan-tRNA ligase activity TAS
    Traceable Author Statement
    more info
    		  
    Process Evidence Code Pubs
    involved_in mitochondrial tryptophanyl-tRNA aminoacylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of angiogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in tRNA aminoacylation for protein translation TAS
    Traceable Author Statement
    more info
    		  
    involved_in vasculogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in mitochondrial matrix IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrial matrix IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    tryptophan--tRNA ligase, mitochondrial
    Names
    (Mt)TrpRS
    tryptophan tRNA ligase 2, mitochondrial
    NP_001365155.1
    NP_001365156.1
    NP_001365157.1
    NP_001365158.1
    NP_001365159.1
    NP_001365160.1
    NP_056651.1
    NP_957715.1
    XP_005270407.1
    XP_016855527.1
    XP_024305594.1
    XP_024305628.1
    XP_047285061.1
    XP_054189785.1
    XP_054189786.1
    XP_054189787.1
    XP_054189788.1

    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_050658.1 RefSeqGene

      Range
      5136..114573
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001378226.1 → NP_001365155.1  tryptophan--tRNA ligase, mitochondrial isoform 3

      Status: REVIEWED

      Source sequence(s)
      AL139420, AL359823, AL590288
      Conserved Domains (1) summary
      PRK00927
      Location:11 → 337
      PRK00927; tryptophanyl-tRNA synthetase; Reviewed

    2. NM_001378227.1 → NP_001365156.1  tryptophan--tRNA ligase, mitochondrial isoform 3

      Status: REVIEWED

      Source sequence(s)
      AL139420, AL359823, AL590288
      Conserved Domains (1) summary
      PRK00927
      Location:11 → 337
      PRK00927; tryptophanyl-tRNA synthetase; Reviewed

    3. NM_001378228.1 → NP_001365157.1  tryptophan--tRNA ligase, mitochondrial isoform 4

      Status: REVIEWED

      Source sequence(s)
      AL139420, AL359823, AL590288
      UniProtKB/TrEMBL
      B7Z6G7
      Conserved Domains (1) summary
      PRK00927
      Location:34 → 303
      PRK00927; tryptophanyl-tRNA synthetase; Reviewed

    4. NM_001378229.1 → NP_001365158.1  tryptophan--tRNA ligase, mitochondrial isoform 5

      Status: REVIEWED

      Source sequence(s)
      AL139420, AL590288
      Conserved Domains (1) summary
      PRK00927
      Location:30 → 274
      PRK00927; tryptophanyl-tRNA synthetase; Reviewed

    5. NM_001378230.1 → NP_001365159.1  tryptophan--tRNA ligase, mitochondrial isoform 6

      Status: REVIEWED

      Source sequence(s)
      AL139420, AL359823, AL590288
      UniProtKB/TrEMBL
      B7Z5X7
      Conserved Domains (1) summary
      PRK00927
      Location:1 → 266
      PRK00927; tryptophanyl-tRNA synthetase; Reviewed

    6. NM_001378231.1 → NP_001365160.1  tryptophan--tRNA ligase, mitochondrial isoform 7

      Status: REVIEWED

      Source sequence(s)
      AL139420, AL359823, AL590288
      UniProtKB/TrEMBL
      B7Z448
      Conserved Domains (1) summary
      PRK00927
      Location:34 → 143
      PRK00927; tryptophanyl-tRNA synthetase; Reviewed

    7. NM_015836.4 → NP_056651.1  tryptophan--tRNA ligase, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_056651.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the shorter transcript but encodes the longer protein (isoform 1).
      Source sequence(s)
      AL139420, AL359823, BC044575
      Consensus CDS
      CCDS900.1
      UniProtKB/Swiss-Prot
      B1ALR1, B2R9D4, Q53FT4, Q5VUD2, Q86TQ0, Q9UGM6
      Related
      ENSP00000235521.4, ENST00000235521.5
      Conserved Domains (1) summary
      PRK00927
      Location:34 → 360
      PRK00927; tryptophanyl-tRNA synthetase; Reviewed

    8. NM_201263.2 → NP_957715.1  tryptophan--tRNA ligase, mitochondrial isoform 2 precursor

      See identical proteins and their annotated locations for NP_957715.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) includes an alternate in-frame segment in the 3' coding region, compared to variant 1, that causes a frameshift. The resulting protein (isoform 2) is shorter and has a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AL139420, AL590288, BC039889
      Consensus CDS
      CCDS30817.1
      UniProtKB/Swiss-Prot
      Q9UGM6
      Related
      ENSP00000358434.5, ENST00000369426.9
      Conserved Domains (1) summary
      PRK00927
      Location:34 → 212
      PRK00927; tryptophanyl-tRNA synthetase; Reviewed

    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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      119031216..119140672 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047429105.1 → XP_047285061.1  tryptophan--tRNA ligase, mitochondrial isoform X4

    2. XM_017000038.2 → XP_016855527.1  tryptophan--tRNA ligase, mitochondrial isoform X2

    3. XM_024449860.2 → XP_024305628.1  tryptophan--tRNA ligase, mitochondrial isoform X5

      UniProtKB/TrEMBL
      B7Z5X7
      Conserved Domains (1) summary
      PRK00927
      Location:1 → 266
      PRK00927; tryptophanyl-tRNA synthetase; Reviewed

    4. XM_024449826.2 → XP_024305594.1  tryptophan--tRNA ligase, mitochondrial isoform X3

      Conserved Domains (1) summary
      PRK00927
      Location:11 → 337
      PRK00927; tryptophanyl-tRNA synthetase; Reviewed

    5. XM_005270350.4 → XP_005270407.1  tryptophan--tRNA ligase, mitochondrial isoform X1

      Conserved Domains (2) summary
      cd00806
      Location:18 → 294
      TrpRS_core; catalytic core domain of tryptophanyl-tRNA synthetase
      PRK00927
      Location:16 → 342
      PRK00927; tryptophanyl-tRNA synthetase; Reviewed

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      119044400..119154015 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054333811.1 → XP_054189786.1  tryptophan--tRNA ligase, mitochondrial isoform X3

    2. XM_054333813.1 → XP_054189788.1  tryptophan--tRNA ligase, mitochondrial isoform X4

    3. XM_054333810.1 → XP_054189785.1  tryptophan--tRNA ligase, mitochondrial isoform X2

    4. XM_054333812.1 → XP_054189787.1  tryptophan--tRNA ligase, mitochondrial isoform X6

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UGM6.1 GenPept UniProtKB/Swiss-Prot:Q9UGM6

    Gene LinkOut

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