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

Gene ID: 10352, updated on 2-Nov-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
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Genomic context

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See WARS2 in Genome Data Viewer
Location:
1p12
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (119031216..119140672, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (119044400..119154015, complement)
RS_2024_09 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 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. 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
  2. Human tryptophanyl-tRNA synthetase is switched to a tRNA-dependent mode for tryptophan activation by mutations at V85 and I311. Guo LT, et al. Nucleic Acids Res, 2007. PMID 17726052, Free PMC Article
  3. A new gamma-interferon-inducible promoter and splice variants of an anti-angiogenic human tRNA synthetase. Liu J, et al. Nucleic Acids Res, 2004. PMID 14757836, Free PMC Article
  4. Deficiency of WARS2, encoding mitochondrial tryptophanyl tRNA synthetase, causes severe infantile onset leukoencephalopathy. Theisen BE, et al. Am J Med Genet A, 2017 Sep. PMID 28650581
  5. 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

See all (43) 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
  
located_in mitochondrion HTP PubMed 
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_2024_08

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

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