GARS1 (glycyl-tRNA synthetase 1)

Gene

• Entrez ID: 2617
• Gene name: Glycyl-tRNA synthetase 1
• Gene symbol: GARS1
• Synonyms (NCBI Gene): CMT2D, DSMAV, GARS, GlyRS, HMN5, HMN5A, HMND5, SMAD1, SMAJI
• Chromosome: 7
• Chromosome location: 7p14.3
• 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 t

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs77518956	G>A	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs137852643	G>C	Uncertain-significance, pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs137852644	T>C	Uncertain-significance, pathogenic	Missense variant, coding sequence variant
rs137852645	A>G	Uncertain-significance, pathogenic	Missense variant, coding sequence variant
rs137852646	G>A,C	Uncertain-significance, pathogenic	Missense variant, coding sequence variant
rs137852647	G>A	Uncertain-significance, pathogenic	Missense variant, coding sequence variant
rs137852648	C>T	Pathogenic	Missense variant, coding sequence variant
rs183573304	C>G,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs192443850	A>G	Likely-pathogenic, conflicting-interpretations-of-pathogenicity, uncertain-significance, likely-benign	Missense variant, coding sequence variant
rs200279483	A>G	Benign-likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs200887429	G>A,T	Conflicting-interpretations-of-pathogenicity, uncertain-significance, likely-benign	Missense variant, coding sequence variant, 5 prime UTR variant
rs201358272	C>G,T	Pathogenic, uncertain-significance, benign	Missense variant, coding sequence variant
rs370057212	C>A,T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, coding sequence variant
rs370608239	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Synonymous variant, coding sequence variant
rs376324026	G>A,C	Conflicting-interpretations-of-pathogenicity, likely-benign, benign, uncertain-significance	Intron variant
rs376772628	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, coding sequence variant
rs762624758	G>A	Likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant, 5 prime UTR variant
rs797044855	G>A,C	Pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs863224873	A>C,G,T	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs886043231	T>C	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs1057519166	C>T	Conflicting-interpretations-of-pathogenicity	5 prime UTR variant, coding sequence variant, synonymous variant
rs1060502838	A>G	Uncertain-significance, pathogenic	Missense variant, coding sequence variant
rs1060502839	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1064795123	T>C,G	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs1135401747	AGAA>-	Pathogenic	5 prime UTR variant, coding sequence variant, frameshift variant
rs1135401748	G>A	Pathogenic	Missense variant, coding sequence variant
rs1554337974	C>T	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs1554338260	A>T	Pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs1554338262	T>A	Pathogenic	Coding sequence variant, missense variant
rs1554338272	G>A	Pathogenic	Splice donor variant
rs1554340340	G>A	Pathogenic	Splice donor variant
rs1584026191	G>C	Likely-pathogenic	Coding sequence variant, missense variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0004081	Function	Bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity	IDA	19710017
GO:0004812	Function	Aminoacyl-tRNA ligase activity	IEA
GO:0004820	Function	Glycine-tRNA ligase activity	IBA
GO:0004820	Function	Glycine-tRNA ligase activity	IDA	17544401, 17545306, 19710017
GO:0004820	Function	Glycine-tRNA ligase activity	IEA
GO:0004820	Function	Glycine-tRNA ligase activity	IMP	28675565
GO:0005515	Function	Protein binding	IPI	17545306, 17595294, 32814053
GO:0005524	Function	ATP binding	IEA
GO:0005576	Component	Extracellular region	IEA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	TAS	7961834
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006412	Process	Translation	IEA
GO:0006418	Process	TRNA aminoacylation for protein translation	IEA
GO:0006418	Process	TRNA aminoacylation for protein translation	IMP	28675565
GO:0006426	Process	Glycyl-tRNA aminoacylation	IEA
GO:0006426	Process	Glycyl-tRNA aminoacylation	IEA
GO:0015966	Process	Diadenosine tetraphosphate biosynthetic process	IDA	19710017
GO:0016740	Function	Transferase activity	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0016874	Function	Ligase activity	IEA
GO:0030141	Component	Secretory granule	IEA
GO:0030424	Component	Axon	IDA	17035524
GO:0030424	Component	Axon	IEA
GO:0042802	Function	Identical protein binding	IPI	17545306, 17595294
GO:0042995	Component	Cell projection	IEA
GO:0046983	Function	Protein dimerization activity	IDA	17544401, 17545306
GO:0070062	Component	Extracellular exosome	IEA
GO:0070062	Component	Extracellular exosome	ISS
GO:0070150	Process	Mitochondrial glycyl-tRNA aminoacylation	IBA
GO:0141192	Function	ATP:ATP adenylyltransferase activity	IEA

Other IDs

• MIM: 600287
• HGNC: 4162
• e!Ensembl: ENSG00000106105

Protein

• UniProt ID: P41250
• Protein name: Glycine--tRNA ligase (EC 6.1.1.14) (Diadenosine tetraphosphate synthetase) (Ap4A synthetase) (EC 2.7.7.-) (Glycyl-tRNA synthetase) (GlyRS) (Glycyl-tRNA synthetase 1)
• Protein function: Catalyzes the ATP-dependent ligation of glycine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (Gly-AMP) (PubMed:17544401, PubMed:24898252, PubMed:28675565). Also produces diadenosine tetraphosphate (
• PDB: 2PME, 2PMF, 2Q5H, 2Q5I, 2ZT5, 2ZT6, 2ZT7, 2ZT8, 2ZXF, 4KQE, 4KR2, 4KR3, 4QEI, 5E6M
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00458	WHEP-TRS	67 → 117	WHEP-TRS domain	Domain
  PF00587	tRNA-synt_2b	291 → 592	tRNA synthetase class II core domain (G, H, P, S and T)	Domain
  PF03129	HGTP_anticodon	615 → 709	Anticodon binding domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed, including in brain and spinal cord. {ECO:0000269|PubMed:12690580}.; TISSUE SPECIFICITY: [Isoform 2]: Expressed in brain, spinal cord, muscle, heart and spleen. {ECO:0000269|PubMed:26327585}.; TISSUE SPECIFICITY: [Isof
• Sequence:

  MPSPRPVLLRGARAALLLLLPPRLLARPSLLLRRSLSAASCPPISLPAAASRSSMDGAGA
  EEVLAPLRLAVRQQGDLVRKLKEDKAPQVDVDKAVAELKARKRVLEAKELALQPKDDIVD
  RAKMEDTLKRRFFYDQAFAIYGGVSGLYDFGPVGCALKNNIIQTWRQHFIQEEQILEIDC
  TMLTPEPVLKTSGHVDKFADFMVKDVKNGECFRADHLLKAHLQKLMSDKKCSVEKKSEME
  SVLAQLDNYGQQELADLFVNYNVKSPITGNDLSPPVSFNLMFKTFIGPGGNMPGYLRPET
  AQGIFLNFKRLLEFNQGKLPFAAAQIGNSFRNEISPRSGLIRVREFTMAEIEHFVDPSEK
  DHPKFQNVADLHLYLYSAKAQVSGQSARKMRLGDAVEQGVINNTVLGYFIGRIYLYLTKV
  GISPDKLRFRQHMENEMAHYACDCWDAESKTSYGWIEIVGCADRSCYDLSCHARATKVPL
  VAEKPLKEPKTVNVVQFEPSKGAIGKAYKKDAKLVMEYLAICDECYITEMEMLLNEKGEF
  TIETEGKTFQLTKDMINVKRFQKTLYVEEVVPNVIEPSFGLGRIMYTVFEHTFHVREGDE
  QRTFFSFPAVVAPFKCSVLPLSQNQEFMPFVKELSEALTRHGVSHKVDDSSGSIGRRYAR
  TDEIGVAFGVTIDFDTVNKTPHTATLRDRDSMRQIRAEISELPSIVQDLANGNITWADVE
  ARYPLFEGQETGKKETIEE

• Sequence length: 739

Pathways

KEGG:

Aminoacyl-tRNA biosynthesis

Reactome:

Cytosolic tRNA aminoacylation
Mitochondrial tRNA aminoacylation

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Charcot-Marie-Tooth disease	Likely pathogenic; Pathogenic	rs137852643, rs137852644, rs1060502838, rs1554338260, rs1554337974, rs1554337369	RCV000789142 RCV000857175 RCV000789777 RCV000789773 RCV000789776 RCV000789775
Charcot-Marie-Tooth disease type 2	Likely pathogenic; Pathogenic	rs2128134030, rs2128134025, rs137852643, rs137852646, rs2534306033, rs1060502838, rs1060502839, rs1064795123, rs1554338260, rs1554337974, rs1554338262, rs1554338641, rs1554337369, rs1584034430	RCV005095142 RCV003032499 RCV000692132 RCV002228024 RCV003581439 RCV000459084 RCV000468725 RCV000558281 RCV000529259 RCV000533118 RCV000653928 RCV000653955 RCV001038534 RCV000819141 RCV001034922 RCV001231694
Charcot-Marie-Tooth disease type 2D	Pathogenic; Likely pathogenic	rs2128134025, rs863224873, rs137852643, rs137852644, rs137852646, rs1060502838, rs1554338260, rs1554338262, rs1584034430, rs1554337974	RCV001838853 RCV000195583 RCV000009782 RCV003332077 RCV001542258 RCV003332179 RCV001542256 RCV001334991 RCV005253645 RCV001265531
Distal spinal muscular atrophy	Pathogenic	rs137852646, rs1060502838, rs1554338260	RCV000790258 RCV000790256 RCV000790255
GARS-associated growth retardation and developmental delay	Pathogenic	rs1135401747	RCV000496467
Neuronopathy, distal hereditary motor, type 5	Pathogenic; Likely pathogenic	rs1554338260, rs1554337974, rs1554337369	RCV003447145 RCV003447146 RCV003447259
Neuronopathy, distal hereditary motor, type 5A	Likely pathogenic; Pathogenic	rs2128134030, rs863224873, rs137852644, rs137852646, rs1060502838, rs1554338260, rs1584026191, rs1584034430	RCV003314018 RCV000195583 RCV000009783 RCV000009786 RCV000664213 RCV001770486 RCV000788053 RCV001823170
Spinal muscular atrophy, infantile, James type	Pathogenic; Likely pathogenic	rs797044855, rs1554338262, rs1783251037	RCV001260977 RCV001260980 RCV001260981

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Acute myeloid leukemia	Benign	rs17159291	RCV005904267
Cervical cancer	Benign; Likely benign	rs189589556	RCV005892541
Charcot-Marie-Tooth disease type 5	Likely benign	rs747338292	RCV000857181
Charcot-Marie-Tooth disease, type I	Conflicting classifications of pathogenicity	rs376324026	RCV000857179
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Benign; Likely benign; Uncertain significance	rs189589556, rs773889809	RCV005892544 RCV005906953
Familial cancer of breast	Benign; Likely benign	rs189589556, rs370844461	RCV005892540 RCV005907162
GARS-Associated Axonal Neuropathy	Uncertain significance	rs864622616, rs370650205, rs750901652	RCV001249739 RCV005863253 RCV001535443
GARS1-related disorder	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	rs2230310, rs201927627, rs2534290407, rs192443850, rs2534305985, rs187937286, rs2534314042, rs1783284312, rs200279483, rs376324026, rs190132116, rs150213018, rs770924455, rs1301948344, rs1554338272, rs960876782, rs1303447354	RCV003917573 RCV003891775 RCV003400050 RCV003922595 RCV003981107 RCV003972514 RCV003896661 RCV003899097 RCV003970177 RCV003959943 RCV003897845 RCV003972793 RCV003892495 RCV005870872 RCV003908089 RCV003975383 RCV005866846
GARS1-related neuropathies	Uncertain significance	rs750901652	RCV001249738
Gastric cancer	Benign	rs17159291	RCV005904269
Hereditary motor neuron disease	Uncertain significance	rs863224873	RCV000789143
Lung cancer	Benign; Likely benign	rs189589556	RCV005892543
Malignant lymphoma, large B-cell, diffuse	Benign	rs17159291	RCV005904268
Motor neuron disease	Uncertain significance	rs1554336520	RCV000664247
Neuronopathy, distal hereditary motor, autosomal dominant	Conflicting classifications of pathogenicity	rs747080824	RCV000789772
Nonpapillary renal cell carcinoma	Likely benign	rs1562783874	RCV005928378
Ovarian serous cystadenocarcinoma	Conflicting classifications of pathogenicity	rs1554338272	RCV005901940
Parkinsonian disorder	Conflicting classifications of pathogenicity	rs774169230	RCV005626612
Peripheral axonal neuropathy	Likely benign; Conflicting classifications of pathogenicity	rs529035174, rs758974790, rs70983380	RCV000353217 RCV000315872 RCV000398108 RCV000280689
Pes cavus	Uncertain significance	rs953786034	RCV003150849
Sarcoma	Benign; Likely benign	rs189589556	RCV005892542
See cases	Conflicting classifications of pathogenicity; Uncertain significance	rs764238525, rs1303447354, rs776528885	RCV004797859 RCV001198686 RCV001198401
Thymoma	Benign	rs17159291	RCV005904271
Tip-toe gait	Conflicting classifications of pathogenicity	rs369894731	RCV002227458
Uterine carcinosarcoma	Benign	rs17159291	RCV005904270

Associations from Text Mining
Disease Name	Relationship Type	References
Atrophy	Associate	22462675
Charcot Marie Tooth Disease	Associate	17142907, 17545306, 21737751, 24669931, 24898252, 28675565, 31173493, 31501329, 33753480, 34403468
Charcot Marie Tooth disease Type 2D	Associate	12690580, 19412816, 22462675, 28594869, 31173493, 31985473, 34958183
Disease	Associate	28675565
Distal Hereditary Motor Neuropathy Type II	Associate	31628756
Down Syndrome	Associate	22931243
Failure to Thrive	Associate	31985473
Feeding and Eating Disorders	Associate	31985473
Genetic Diseases Inborn	Associate	12690580, 17544401
Growth Disorders	Associate	28675565
Heredodegenerative Disorders Nervous System	Associate	26797133
Hyperekplexia	Associate	35526563
Hyperexplexia hereditary	Associate	7518444
Isolated Noncompaction of the Ventricular Myocardium	Associate	24669931
Liver Cirrhosis	Associate	29666468
Lymphatic Metastasis	Stimulate	36901698
Mitochondrial Diseases	Associate	24669931, 25058219, 28594869
Motor Neuron Disease	Associate	12690580
Multiple System Atrophy	Associate	28675565
Muscle Weakness	Associate	22462675, 31628756
Muscular Atrophy Spinal	Associate	17544401, 24669931, 32181591
Neoplasms	Associate	27348078
Neoplastic Syndromes Hereditary	Associate	31985473
Nerve Degeneration	Associate	17544401
Nervous System Diseases	Associate	31985473
Neuronopathy Distal Hereditary Motor Type I	Associate	19412816
Neuronopathy Distal Hereditary Motor Type V	Associate	12690580, 17663003, 22462675, 28594869, 31985473
Peripheral Nervous System Diseases	Associate	21737751
Prostatic Neoplasms	Associate	36901698
Shoulder Fractures	Associate	31628756
Spastic Paraplegia Hereditary	Associate	19412816, 22462675
Spinal muscular atrophy Jerash type	Associate	31628756
Stiff Person Syndrome	Associate	28174298