GARS glycyl-tRNA synthetase [Homo sapiens] - Gene

Help top of page

Summary

Official Symbol: GARSprovided by HGNC
Official Full Name: glycyl-tRNA synthetaseprovided by HGNC
Primary source: HGNC:4162
See related: Ensembl:ENSG00000106105; HPRD:02617; MIM:600287; Vega:OTTHUMG00000152769
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: HMN5; CMT2D; DSMAV; GlyRS; SMAD1
Summary: This gene encodes glycyl-tRNA synthetase, one of the aminoacyl-tRNA synthetases that charge tRNAs with their cognate amino acids. The encoded enzyme is an (alpha)2 dimer which belongs to the class II family of tRNA synthetases. It has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis. [provided by RefSeq, Jul 2008]

Help top of page

Genomic context

Location :: 7p15

Sequence :: Chromosome: 7; NC_000007.13 (30634181..30673649)

See GARS in Epigenomics, MapViewer

Chromosome 7 - NC_000007.13 Genomic Context describing neighboring genes

Help top of page

Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Help top of page

Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

GRS bound to different ERK-activated tumor cells, and released phosphatase 2A (PP2A) from CDH6.
Title: Secreted human glycyl-tRNA synthetase implicated in defense against ERK-activated tumorigenesis.
missense mutations of Gars may cause some loss of function, the dominant neuropathy phenotype observed in mice is caused by a dose-dependent gain of function that is not mitigated by over-expression of functional wild-type protein.
Title: Charcot-Marie-Tooth-linked mutant GARS is toxic to peripheral neurons independent of wild-type GARS levels.
No pathogenic mutations were found, excluding the role of GARS gene as a possible factor in the aetiology of Hirayama disease in this cohort
Title: Mutational analysis of glycyl-tRNA synthetase (GARS) gene in Hirayama disease.
GARS mutation is a rare cause of Charcot-Marie-Tooth neuropathy among Japanese patients.
Title: The GARS gene is rarely mutated in Japanese patients with Charcot-Marie-Tooth neuropathy.
human glycyl-tRNA synthetase has a role in Ap4A homeostasis
Title: Crystal structures and biochemical analyses suggest a unique mechanism and role for human glycyl-tRNA synthetase in Ap4A homeostasis.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
we present a comparison between the crystal structures of the eubacterial Escherichia coli and the human tRNA(Gly) acceptor stem microhelices and their surrounding hydration patterns.
Title: Comparative X-ray structure analysis of human and Escherichia coli tRNA(Gly) acceptor stem microhelices.
Charcot-Marie-Tooth (CMT) disease-causing mutations of glycine-tRNA synthetase share a common defect in localization which may be connected to a change in surfaces at the dimer interface, and may cause a dominant axonal form of CMT (type 2D).
Title: Charcot-Marie-Tooth disease-associated mutant tRNA synthetases linked to altered dimer interface and neurite distribution defect.
A novel heterozygous missense GARS gene mutation (D500N) was identified in members of a family affected byCharcot-Marie-Tooth type 2D.
Title: Coexistence of CMT-2D and distal SMA-V phenotypes in an Italian family with a GARS gene mutation.
Four disease-associated missense mutations in the glycyl tRNA synthetase gene in families with Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V
Title: Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V.

Submit: New GeneRIF Correction See all (14)

Help top of page

Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Charcot-Marie-Tooth disease, type 2D

MIM: 601472

GARS-associated axonal neuropathy (Charcot-Marie-Tooth neuropathy type 2D/distal spinal muscular atrophy V [CMT2D/dSMA-V]) is characterized by adolescent or early-adult onset of bilateral weakness and atrophy of thenar and first dorsal interosseus muscles, sparing of the hypothenar eminence until later in the course of illness, and mild to moderate impairment of vibration sense in the hands and feet later in the disease course in a minority of individuals. The phenotype is considered the CMT2D subtype when sensory deficits (reduction of pinprick, temperature, touch, and vibration perception in a stocking and [less often] glove pattern) are present and dSMA-V when sensory deficits are absent. The lower limbs are involved in about half of affected individuals. The earliest elicited manifestations in many individuals are transient cramping and pain in the hands on exposure to cold and cramping in calf muscles on exertion.

Diagnosis Testing

The diagnosis of GARS-associated axonal neuropathy is based on clinical findings, electromyography (EMG), and molecular genetic testing of GARS, encoding glycyl-tRNA synthetase.

Genetic Counseling

GARS-associated axonal neuropathy is inherited in an autosomal dominant manner. Most individuals diagnosed with the disorder have an affected parent. The proportion of cases caused by de novo mutations is unknown. Each child of an individual with GARS-associated axonal neuropathy has a 50% chance of inheriting the mutation. Prenatal testing is available for families in which the disease-causing mutation has been identified in an affected family member.

References

PMID: 20301420

Neuropathy, distal hereditary motor, type V

MIM: 600794

Help top of page

Interactions

Products	Interactant	Other Gene	Source	Pubs	Description
NP_002038.1		EEF1D	BIND	PubMed	GRS interacts with an unspecified isoform of EF-1-delta.
P41250	P16070	CD44	HPRD	PubMed
P41250	Q9HCU4	CELSR2	HPRD	PubMed
P41250	P29692	EEF1D	HPRD	PubMed
P41250	P41252	IARS	HPRD	PubMed
BioGRID:108887	BioGRID:108256	EEF1D	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:108887	BioGRID:200263	Hdac6	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108887	BioGRID:109605	IARS	BioGRID	PubMed	Two-hybrid
BioGRID:108887	BioGRID:111657	PSMA3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108887	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Help top of page

General gene information

Markers

D7S1808 (e-PCR)
- UniSTS:25378

SHGC-31691 (e-PCR)
- UniSTS:59459

D7S2049E (e-PCR)
- UniSTS:151112

BARC0022 (e-PCR)
- UniSTS:255308

GARS (e-PCR)
- UniSTS:503631

RH47187 (e-PCR)
- UniSTS:9306

RH47185 (e-PCR)
- UniSTS:43417

D7S435 (e-PCR), detects polymorphism
- UniSTS:76188

D7S2836 (e-PCR)
- UniSTS:3558

Genotypes

See GARS SNP Geneview Report
See GARS SNP Genotype Report
See GARS SNP Variation Viewer Report

Related pseudogene(s)

1 found Review record(s) in Gene

Homology

Homologs of the GARS gene: The GARS gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, , S.pombe, , N.crassa, A.thaliana, rice, and P.falciparum.
Map Viewer (Mouse, Rat)

Pathways from BioSystems

Aminoacyl-tRNA biosynthesis, organism-specific biosystem (from KEGG)
Aminoacyl-tRNA biosynthesis, organism-specific biosystem
Aminoacyl-tRNA biosynthesis
Aminoacyl-tRNA biosynthesis, conserved biosystem (from KEGG)
Aminoacyl-tRNA biosynthesis, conserved biosystem
Aminoacyl-tRNA biosynthesis
Aminoacyl-tRNA biosynthesis, eukaryotes, organism-specific biosystem (from KEGG)
Aminoacyl-tRNA biosynthesis, eukaryotes, organism-specific biosystemFunctional set; Metabolism; Aminoacyl tRNA
Aminoacyl-tRNA biosynthesis, eukaryotes, conserved biosystem (from KEGG)
Aminoacyl-tRNA biosynthesis, eukaryotes, conserved biosystemFunctional set; Metabolism; Aminoacyl tRNA
Cytosolic tRNA aminoacylation, organism-specific biosystem (from REACTOME)
Cytosolic tRNA aminoacylation, organism-specific biosystemCytosolic tRNA synthetases catalyze the reactions of tRNAs encoded in the nuclear genome, their cognate amino acids, and ATP to form aminoacyl-tRNAs, AMP, and pyrophosphate. Eight of the tRNA synthet...
Gene Expression, organism-specific biosystem (from REACTOME)
Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
Mitochondrial tRNA aminoacylation, organism-specific biosystem (from REACTOME)
Mitochondrial tRNA aminoacylation, organism-specific biosystemMitochondrial tRNA synthetases act in the mitochondrial matrix to catalyze the reactions of tRNAs encoded in the mitochondrial genome, their cognate amino acids, and ATP to form aminoacyl-tRNAs, AMP,...
tRNA Aminoacylation, organism-specific biosystem (from REACTOME)
tRNA Aminoacylation, organism-specific biosystemtRNA synthetases catalyze the ligation of tRNAs to their cognate amino acids in an ATP-dependent manner. The reaction proceeds in two steps. First, amino acid and ATP form an aminoacyl adenylate mole...

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
glycine-tRNA ligase activity	IDA Inferred from Direct Assay more info	PubMed
glycine-tRNA ligase activity	TAS Traceable Author Statement more info
ligase activity	IEA Inferred from Electronic Annotation more info
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein dimerization activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
cell death	IEA Inferred from Electronic Annotation more info
diadenosine tetraphosphate biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
gene expression	TAS Traceable Author Statement more info
glycyl-tRNA aminoacylation	IEA Inferred from Electronic Annotation more info
tRNA aminoacylation for protein translation	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info
mitochondrial matrix	TAS Traceable Author Statement more info
mitochondrion	IEA Inferred from Electronic Annotation more info
secretory granule	IEA Inferred from Electronic Annotation more info
soluble fraction	TAS Traceable Author Statement more info	PubMed

Help top of page

General protein information

Preferred Names: glycine--tRNA ligase

Names: glycine--tRNA ligase; AP-4-A synthetase; glycine tRNA ligase; Charcot-Marie-Tooth neuropathy 2D; diadenosine tetraphosphate synthetase; Charcot-Marie-Tooth neuropathy, neuronal type, D

NP_002038.2

EC 6.1.1.14

Help top of page

NCBI Reference Sequences (RefSeq)

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

NG_007942.1 RefSeqGene

Range

5001..44469

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_002047.2 → NP_002038.2 glycine--tRNA ligase precursor

Status: REVIEWED

Source sequence(s)

AA772440, AC005154, AK074524, BC007755, U09510

Consensus CDS

CCDS43564.1

UniProtKB/Swiss-Prot

P41250

Related

ENSP00000373918, OTTHUMP00000202329, ENST00000389266, OTTHUMT00000327735

Conserved Domains (5) summary

cd00858
Location:588 – 711
Blast Score: 438

GlyRS_anticodon; GlyRS Glycyl-anticodon binding domain. GlyRS belongs to class II aminoacyl-tRNA synthetases (aaRS). This alignment contains the anticodon binding domain, which is responsible for specificity in tRNA-binding, so that the activated amino acid is ...

cd00935
Location:64 – 114
Blast Score: 221

GlyRS_RNA; GlyRS_RNA binding domain. This short RNA-binding domain is found at the N-terminus of GlyRS in several higher eukaryote aminoacyl-tRNA synthetases (aaRSs). This domain consists of a helix-turn-helix structure , which is similar to other RNA-binding ...

cd00774
Location:280 – 470
Blast Score: 728

GlyRS-like_core; Glycyl-tRNA synthetase (GlyRS)-like class II core catalytic domain. GlyRS functions as a homodimer in eukaryotes, archaea and some bacteria and as a heterotetramer in the remainder of prokaryotes. It is responsible for the attachment of glycine to the 3' ...

PLN02734
Location:61 – 724
Blast Score: 2327

PLN02734; glycyl-tRNA synthetase

cl00268
Location:124 – 197
Blast Score: 271

class_II_aaRS-like_core; Class II tRNA amino-acyl synthetase-like catalytic core domain. Class II amino acyl-tRNA synthetases (aaRS) share a common fold and generally attach an amino acid to the 3' OH of ribose of the appropriate tRNA. PheRS is an exception in that it attaches ...

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000007.13 Reference GRCh37.p5 Primary Assembly

Range

30634181..30673649

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000139.1 Alternate HuRef

Range

30516030..30555489

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CRA_TCAGchr7v2

Genomic

AC_000068.1 Alternate CRA_TCAGchr7v2

Range

30683834..30723301

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Help top of page

Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AACC02000087.1	EAL24449.1
genomic	AC004976.1	AAC71652.1
genomic	AC005154.1 (137163..146170)	None
genomic	AC006969.2	AAS00367.1
genomic	CH471073.1	EAW93960.1
		EAW93961.1
mRNA	AA772440.1	None
mRNA	AK074524.1	BAG51964.1
mRNA	AK295490.1	BAG58412.1
mRNA	AK310351.1	None
mRNA	BC000065.1	None
mRNA	BC007722.2	AAH07722.1
mRNA	BC007755.2	AAH07755.1
mRNA	D30658.1	BAA06338.1
mRNA	U09510.1	AAA86443.1
mRNA	U09587.1	AAA57001.1
other-genetic	DQ892773.2	ABM83699.1
other-genetic	DQ896021.2	ABM87020.1