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RARS2 arginyl-tRNA synthetase 2, mitochondrial [ Homo sapiens (human) ]

Gene ID: 57038, updated on 3-Apr-2024

Summary

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Official Symbol
RARS2provided by HGNC
Official Full Name
arginyl-tRNA synthetase 2, mitochondrialprovided by HGNC
Primary source
HGNC:HGNC:21406
See related
Ensembl:ENSG00000146282 MIM:611524; AllianceGenome:HGNC:21406
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
PCH6; ArgRS; RARSL; DALRD2; PRO1992
Summary
This nuclear gene encodes a protein that localizes to the mitochondria, where it catalyzes the transfer of L-arginine to its cognate tRNA, an important step in translation of mitochondrially-encoded proteins. Defects in this gene are a cause of pontocerebellar hypoplasia type 6 (PCH6). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
Expression
Ubiquitous expression in adrenal (RPKM 9.8), testis (RPKM 8.4) and 25 other tissues See more
Orthologs
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Genomic context

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See RARS2 in Genome Data Viewer
Location:
6q15
Exon count:
26
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (87513938..87589987, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (88722691..88798283, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (88223656..88299705, complement)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124901357 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:88182339-88183245 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24795 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24796 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr6:88193750-88194949 Neighboring gene solute carrier family 35 member A1 Neighboring gene RNA, U6 small nuclear 444, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24797 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:88298835-88299796 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:88301170-88301670 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:88301671-88302171 Neighboring gene NANOG hESC enhancer GRCh37_chr6:88313800-88314301 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:88323459-88323960 Neighboring gene origin recognition complex subunit 3 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:88349062-88349578 Neighboring gene MPRA-validated peak5943 silencer Neighboring gene akirin 2 Neighboring gene NANOG hESC enhancer GRCh37_chr6:88408207-88408726 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17375 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17376 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24799 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24800 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24801 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24802 Neighboring gene small nucleolar RNA U13

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. Novel RARS2 Variants: Updating the Diagnosis and Pathogenesis of Pontocerebellar Hypoplasia Type 6. Zhang Y, et al. Pediatr Neurol, 2022 Jun. PMID 35468344
  2. Novel homozygous RARS2 mutation in two siblings without pontocerebellar hypoplasia - further expansion of the phenotypic spectrum. Lühl S, et al. Orphanet J Rare Dis, 2016 Oct 21. PMID 27769281, Free PMC Article
  3. RARS2 mutations cause early onset epileptic encephalopathy without ponto-cerebellar hypoplasia. Nishri D, et al. Eur J Paediatr Neurol, 2016 May. PMID 26970947
  4. Neuropathologic Characterization of Pontocerebellar Hypoplasia Type 6 Associated With Cardiomyopathy and Hydrops Fetalis and Severe Multisystem Respiratory Chain Deficiency due to Novel RARS2 Mutations. Lax NZ, et al. J Neuropathol Exp Neurol, 2015 Jul. PMID 26083569, Free PMC Article
  5. A novel mutation in the promoter of RARS2 causes pontocerebellar hypoplasia in two siblings. Li Z, et al. J Hum Genet, 2015 Jul. PMID 25809939, Free PMC Article

See all (49) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Clinical and genetic analysis of infants with pontocerebellar hypoplasia type 6 caused by RARS2 variations.
    Title: Clinical and genetic analysis of infants with pontocerebellar hypoplasia type 6 caused by RARS2 variations.
  2. Novel RARS2 Variants: Updating the Diagnosis and Pathogenesis of Pontocerebellar Hypoplasia Type 6.
    Title: Novel RARS2 Variants: Updating the Diagnosis and Pathogenesis of Pontocerebellar Hypoplasia Type 6.
  3. Whole-exome sequencing in adult patients with developmental and epileptic encephalopathy: It is never too late.
    Title: Whole-exome sequencing in adult patients with developmental and epileptic encephalopathy: It is never too late.
  4. Characteristic neuroradiological abnormalities of PCH6 such as vermis and cerebellar hypoplasia and progressive pontocerebellar atrophy may be missing in patients with RARS2 mutations
    Title: Novel homozygous RARS2 mutation in two siblings without pontocerebellar hypoplasia - further expansion of the phenotypic spectrum.
  5. RARS2 gene mutations can cause a metabolic neurodegenerative disease manifesting primarily as early onset epileptic encephalopathies with post-natal microcephaly, without pontocerebellar hypoplasia.
    Title: RARS2 mutations cause early onset epileptic encephalopathy without ponto-cerebellar hypoplasia.
  6. Mutations in the RARS2 promoter are likely to represent a new causal mechanism of pontocerebellar hypoplasia.
    Title: A novel mutation in the promoter of RARS2 causes pontocerebellar hypoplasia in two siblings.
  7. Molecular investigations of RARS2 disclosed the c.25A>G/p.I9V and the c.1586+3A>T in family A.
    Title: Pontocerebellar hypoplasia type 6 caused by mutations in RARS2: definition of the clinical spectrum and molecular findings in five patients.
  8. mutations in the gene encoding mitochondrial arginyl-tRNA synthetase, RARS2, may have a role in pontocerebellar hypoplasia type 6 [case report]
    Title: Further delineation of pontocerebellar hypoplasia type 6 due to mutations in the gene encoding mitochondrial arginyl-tRNA synthetase, RARS2.
  9. Observational study of gene-disease association. (HuGE Navigator)
    Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
Submit: New GeneRIF Correction

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
Pontocerebellar hypoplasia type 6
MedGen: C1969084 OMIM: 611523 GeneReviews: Not available
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EBI GWAS Catalog

Description
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
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

Clone Names

  • MGC14993, MGC23778

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables RNA binding HDA PubMed 
enables arginine-tRNA ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables arginine-tRNA ligase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables arginine-tRNA ligase activity TAS
Traceable Author Statement
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in arginyl-tRNA aminoacylation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in mitochondrial translation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in tRNA aminoacylation for protein translation TAS
Traceable Author Statement
more info
  
Component Evidence Code Pubs
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
located_in mitochondrial membrane IMP
Inferred from Mutant Phenotype
more info
 PubMed 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
probable arginine--tRNA ligase, mitochondrial
Names
probable arginyl-tRNA synthetase, mitochondrial
NP_001305714.1
NP_001337434.1
NP_001337435.1
NP_001337436.1
NP_001337437.1
NP_001337438.1
NP_001337439.1
NP_001337440.1
NP_064716.2
XP_011534251.1
XP_016866562.1
XP_016866563.1
XP_047275048.1
XP_047275049.1
XP_047275050.1
XP_047275051.1
XP_054211932.1
XP_054211933.1
XP_054211934.1
XP_054211935.1
XP_054211936.1
XP_054211937.1
XP_054211938.1

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_008601.1 RefSeqGene

    Range
    5031..81080
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001318785.2 → NP_001305714.1  probable arginine--tRNA ligase, mitochondrial isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate splice site and lacks an alternate exon in the 5' region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus than isoform 1.
    Source sequence(s)
    BC105784, CA314872, CB177631, DB455377
    Consensus CDS
    CCDS93968.1
    UniProtKB/TrEMBL
    A0A8I5KQV7, H0UI22, H0UI23
    Related
    ENSP00000509195.1, ENST00000693327.1
    Conserved Domains (1) summary
    COG0018
    Location:2 → 403
    ArgS; Arginyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

  2. NM_001350505.2 → NP_001337434.1  probable arginine--tRNA ligase, mitochondrial isoform 3 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) encodes the longest isoform (3).
    Source sequence(s)
    AL049697, AL451126
    Consensus CDS
    CCDS93970.1
    UniProtKB/TrEMBL
    A0A8I5KP51, A0A8I5KWC6
    Related
    ENSP00000509453.1, ENST00000691725.1
    Conserved Domains (1) summary
    cl27258
    Location:36 → 576
    tRNA-synt_1d; tRNA synthetases class I (R)

  3. NM_001350506.2 → NP_001337435.1  probable arginine--tRNA ligase, mitochondrial isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) encodes isoform 4.
    Source sequence(s)
    AL049697, AL451126
    Consensus CDS
    CCDS93969.1
    UniProtKB/TrEMBL
    A0A8I5KPZ0, A0A8I5KQV7
    Related
    ENSP00000509147.1, ENST00000693431.1
    Conserved Domains (1) summary
    cl27258
    Location:2 → 401
    tRNA-synt_1d; tRNA synthetases class I (R)

  4. NM_001350507.2 → NP_001337436.1  probable arginine--tRNA ligase, mitochondrial isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6), as well as variants 2 and 7-10, encodes isoform 2.
    Source sequence(s)
    AL049697, AL451126
    Consensus CDS
    CCDS93968.1
    UniProtKB/TrEMBL
    A0A8I5KQV7, H0UI22, H0UI23
    Related
    ENSP00000509026.1, ENST00000685408.1
    Conserved Domains (1) summary
    COG0018
    Location:2 → 403
    ArgS; Arginyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

  5. NM_001350508.2 → NP_001337437.1  probable arginine--tRNA ligase, mitochondrial isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7), as well as variants 2, 6, and 8-10, encodes isoform 2.
    Source sequence(s)
    AL049697, AL451126
    Consensus CDS
    CCDS93968.1
    UniProtKB/TrEMBL
    A0A8I5KQV7, H0UI22, H0UI23
    Conserved Domains (1) summary
    COG0018
    Location:2 → 403
    ArgS; Arginyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

  6. NM_001350509.2 → NP_001337438.1  probable arginine--tRNA ligase, mitochondrial isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8), as well as variants 2, 6, 7, 9, and 10, encodes isoform 2.
    Source sequence(s)
    AL049697, AL451126
    Consensus CDS
    CCDS93968.1
    UniProtKB/TrEMBL
    A0A8I5KQV7, H0UI22, H0UI23
    Conserved Domains (1) summary
    COG0018
    Location:2 → 403
    ArgS; Arginyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

  7. NM_001350510.2 → NP_001337439.1  probable arginine--tRNA ligase, mitochondrial isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (9), as well as variants 2, 6-8, and 10, encodes isoform 2.
    Source sequence(s)
    AL049697, AL451126
    Consensus CDS
    CCDS93968.1
    UniProtKB/TrEMBL
    A0A8I5KQV7, H0UI22, H0UI23
    Related
    ENSP00000510542.1, ENST00000689174.1
    Conserved Domains (1) summary
    COG0018
    Location:2 → 403
    ArgS; Arginyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

  8. NM_001350511.2 → NP_001337440.1  probable arginine--tRNA ligase, mitochondrial isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (10), as well as variants 2 and 6-9, encodes isoform 2.
    Source sequence(s)
    AL049697, AL451126
    Consensus CDS
    CCDS93968.1
    UniProtKB/TrEMBL
    A0A8I5KQV7, H0UI22, H0UI23
    Related
    ENSP00000389656.2, ENST00000451155.2
    Conserved Domains (1) summary
    COG0018
    Location:2 → 403
    ArgS; Arginyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

  9. NM_020320.5 → NP_064716.2  probable arginine--tRNA ligase, mitochondrial isoform 1 precursor

    See identical proteins and their annotated locations for NP_064716.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform 1.
    Source sequence(s)
    AK315669, CA314872, CB177631, DB455377
    Consensus CDS
    CCDS5011.1
    UniProtKB/Swiss-Prot
    B2RDT7, Q5T160, Q96FU5, Q9H8K8
    UniProtKB/TrEMBL
    A0A8I5KP51
    Related
    ENSP00000358549.5, ENST00000369536.10
    Conserved Domains (1) summary
    COG0018
    Location:36 → 578
    ArgS; Arginyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

RNA

  1. NR_134857.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate internal splice site compared to variant 1. This variant is represented as non-coding because use of the expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    BC022341, CA314872, CB177631
    Related
    ENST00000686988.1

  2. NR_146738.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126
    Related
    ENST00000689206.1

  3. NR_146739.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126
    Related
    ENST00000691815.1

  4. NR_146740.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126
    Related
    ENST00000690622.1

  5. NR_146741.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126

  6. NR_146742.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126
    Related
    ENST00000690884.1

  7. NR_146743.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126
    Related
    ENST00000685701.1

  8. NR_146744.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126
    Related
    ENST00000685069.1

  9. NR_146745.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126

  10. NR_146746.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126
    Related
    ENST00000685881.1

  11. NR_146747.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126

  12. NR_146748.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126
    Related
    ENST00000685376.1

  13. NR_146749.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126

  14. NR_146750.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126

  15. NR_146751.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126

  16. NR_146752.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126

  17. NR_146753.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126

  18. NR_146754.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126

  19. NR_146755.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126

  20. NR_146756.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126

  21. NR_146757.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126

  22. NR_146758.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126

  23. NR_146759.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL049697, AL451126
    Related
    ENST00000688532.1

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_000006.12 Reference GRCh38.p14 Primary Assembly

    Range
    87513938..87589987 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047419092.1 → XP_047275048.1  probable arginine--tRNA ligase, mitochondrial isoform X2

    UniProtKB/TrEMBL
    A0A8I5KPZ0

  2. XM_017011073.2 → XP_016866562.1  probable arginine--tRNA ligase, mitochondrial isoform X2

    UniProtKB/TrEMBL
    A0A8I5KPZ0, A0A8I5KQV7
    Conserved Domains (1) summary
    cl27258
    Location:2 → 401
    tRNA-synt_1d; tRNA synthetases class I (R)

  3. XM_017011074.3 → XP_016866563.1  probable arginine--tRNA ligase, mitochondrial isoform X2

    UniProtKB/TrEMBL
    A0A8I5KPZ0, A0A8I5KQV7
    Conserved Domains (1) summary
    cl27258
    Location:2 → 401
    tRNA-synt_1d; tRNA synthetases class I (R)

  4. XM_047419093.1 → XP_047275049.1  probable arginine--tRNA ligase, mitochondrial isoform X2

    UniProtKB/TrEMBL
    A0A8I5KPZ0

  5. XM_047419094.1 → XP_047275050.1  probable arginine--tRNA ligase, mitochondrial isoform X2

    UniProtKB/TrEMBL
    A0A8I5KPZ0

  6. XM_011535949.4 → XP_011534251.1  probable arginine--tRNA ligase, mitochondrial isoform X1

    Conserved Domains (3) summary
    cd00671
    Location:126 → 388
    ArgRS_core; catalytic core domain of arginyl-tRNA synthetases
    pfam00750
    Location:124 → 449
    tRNA-synt_1d; tRNA synthetases class I (R)
    cl12020
    Location:425 → 472
    Anticodon_Ia_like; Anticodon-binding domain of class Ia aminoacyl tRNA synthetases and similar domains

  7. XM_047419095.1 → XP_047275051.1  probable arginine--tRNA ligase, mitochondrial isoform X3

    Related
    ENSP00000509592.1, ENST00000692843.1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060930.1 Alternate T2T-CHM13v2.0

    Range
    88722691..88798283 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054355959.1 → XP_054211934.1  probable arginine--tRNA ligase, mitochondrial isoform X2

  2. XM_054355958.1 → XP_054211933.1  probable arginine--tRNA ligase, mitochondrial isoform X2

  3. XM_054355960.1 → XP_054211935.1  probable arginine--tRNA ligase, mitochondrial isoform X2

  4. XM_054355961.1 → XP_054211936.1  probable arginine--tRNA ligase, mitochondrial isoform X2

  5. XM_054355962.1 → XP_054211937.1  probable arginine--tRNA ligase, mitochondrial isoform X2

  6. XM_054355957.1 → XP_054211932.1  probable arginine--tRNA ligase, mitochondrial isoform X1

  7. XM_054355963.1 → XP_054211938.1  probable arginine--tRNA ligase, mitochondrial isoform X3

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_014107.1: Suppressed sequence

    Description
    NM_014107.1: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q5T160.1 GenPept UniProtKB/Swiss-Prot:Q5T160

Gene LinkOut

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