MARS1 (methionyl-tRNA synthetase 1)

Gene

• Entrez ID: 4141
• Gene name: Methionyl-tRNA synthetase 1
• Gene symbol: MARS1
• Synonyms (NCBI Gene): CMT2U, ILFS2, ILLD, MARS, METRS, MRS, MTRNS, SPG70, TTD9
• Chromosome: 12
• Chromosome location: 12q13.3
• Summary: This gene encodes a member of the class I family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. The encoded protein is a component of the multi-tRNA synthetase co

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs113808165	G>A,T	Conflicting-interpretations-of-pathogenicity, likely-benign	Non coding transcript variant, coding sequence variant, missense variant
rs140467171	T>C	Likely-pathogenic, not-provided, pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs141340466	G>A	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs758523839	A>G	Likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs766466297	A>G	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs781249411	C>A	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000049	Function	TRNA binding	IEA
GO:0000166	Function	Nucleotide binding	IEA
GO:0003723	Function	RNA binding	IEA
GO:0004812	Function	Aminoacyl-tRNA ligase activity	IEA
GO:0004825	Function	Methionine-tRNA ligase activity	IBA
GO:0004825	Function	Methionine-tRNA ligase activity	IDA	11714285
GO:0004825	Function	Methionine-tRNA ligase activity	IEA
GO:0004825	Function	Methionine-tRNA ligase activity	TAS	8921912
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IEA
GO:0005730	Component	Nucleolus	IDA	10791971
GO:0005730	Component	Nucleolus	IEA
GO:0005737	Component	Cytoplasm	IDA	10791971, 22424946
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	IDA	19289464
GO:0005829	Component	Cytosol	IEA
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	TAS
GO:0006431	Process	Methionyl-tRNA aminoacylation	IBA
GO:0006431	Process	Methionyl-tRNA aminoacylation	IDA	11714285
GO:0006431	Process	Methionyl-tRNA aminoacylation	IEA
GO:0006431	Process	Methionyl-tRNA aminoacylation	IMP	33909043
GO:0009303	Process	RRNA transcription	IMP	10791971
GO:0016020	Component	Membrane	HDA	19946888
GO:0016874	Function	Ligase activity	IEA
GO:0017101	Component	Aminoacyl-tRNA synthetase multienzyme complex	IBA
GO:0017101	Component	Aminoacyl-tRNA synthetase multienzyme complex	IDA	10791971, 19131329
GO:0017101	Component	Aminoacyl-tRNA synthetase multienzyme complex	IEA
GO:0036120	Process	Cellular response to platelet-derived growth factor stimulus	IDA	10791971
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:0071364	Process	Cellular response to epidermal growth factor stimulus	IDA	10791971
GO:1901838	Process	Positive regulation of transcription of nucleolar large rRNA by RNA polymerase I	IMP	10791971

Other IDs

• MIM: 156560
• HGNC: 6898
• e!Ensembl: ENSG00000166986

Protein

• UniProt ID: P56192
• Protein name: Methionine--tRNA ligase, cytoplasmic (EC 6.1.1.10) (Methionyl-tRNA synthetase) (MetRS)
• Protein function: Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA (PubMed:11714285). Plays a role in the
• PDB: 2DJV, 4BL7, 4BVX, 4BVY, 5GL7, 5GOY, 5Y6L
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF18485	GST_N_5	1 → 74	Glutathione S-transferase, N-terminal domain	Domain
  PF00043	GST_C	92 → 180	Glutathione S-transferase, C-terminal domain	Domain
  PF09334	tRNA-synt_1g	266 → 658	tRNA synthetases class I (M)	Family
  PF00458	WHEP-TRS	845 → 897	WHEP-TRS domain	Domain

• Sequence:

  MRLFVSDGVPGCLPVLAAAGRARGRAEVLISTVGPEDCVVPFLTRPKVPVLQLDSGNYLF
  STSAICRYFFLLSGWEQDDLTNQWLEWEATELQPALSAALYYLVVQGKKGEDVLGSVRRA
  LTHIDHSLSRQNCPFLAGETESLADIVLWGALYPLLQDPAYLPEELSALHSWFQTLSTQE
  PCQRAAETVLKQQGVLALRPYLQKQPQPSPAEGRAVTNEPEEEELATLSEEEIAMAVTAW
  EKGLESLPPLRPQQNPVLPVAGERNVLITSALPYVNNVPHLGNIIGCVLSADVFARYSRL
  RQWNTLYLCGTDEYGTATETKALEEGLTPQEICDKYHIIHADIYRWFNISFDIFGRTTTP
  QQTKITQDIFQQLLKRGFVLQDTVEQLRCEHCARFLADRFVEGVCPFCGYEEARGDQCDK
  CGKLINAVELKKPQCKVCRSCPVVQSSQHLFLDLPKLEKRLEEWLGRTLPGSDWTPNAQF
  ITRSWLRDGLKPRCITRDLKWGTPVPLEGFEDKVFYVWFDATIGYLSITANYTDQWERWW
  KNPEQVDLYQFMAKDNVPFHSLVFPCSALGAEDNYTLVSHLIATEYLNYEDGKFSKSRGV
  GVFGDMAQDTGIPADIWRFYLLYIRPEGQDSAFSWTDLLLKNNSELLNNLGNFINRAGMF
  VSKFFGGYVPEMVLTPDDQRLLAHVTLELQHYHQLLEKVRIRDALRSILTISRHGNQYIQ
  VNEPWKRIKGSEADRQRAGTVTGLAVNIAALLSVMLQPYMPTVSATIQAQLQLPPPACSI
  LLTNFLCTLPAGHQIGTVSPLFQKLENDQIESLRQRFGGGQAKTSPKPAVVETVTTAKPQ
  QIQALMDEVTKQGNIVRELKAQKADKNEVAAEVAKLLDLKKQLAVAEGKPPEAPKGKKKK
  

• Sequence length: 900

Pathways

KEGG:

Selenocompound metabolism
Aminoacyl-tRNA biosynthesis
Metabolic pathways

Reactome:

Cytosolic tRNA aminoacylation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Charcot-Marie-Tooth disease axonal type 2U	Pathogenic	rs2140038700	RCV001391547	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Germ cell tumor of testis	Pathogenic	rs2540255891	RCV005931950	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Pulmonary alveolar proteinosis	Pathogenic	rs756021768	RCV000169766	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency	Likely pathogenic; Pathogenic	rs774227542, rs756021768, rs758523839	RCV001647325 RCV000173001 RCV000677355	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Spastic paraplegia 70, autosomal recessive	Pathogenic	rs2540290892	RCV003223368	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL DOMINANT CHARCOT-MARIE-TOOTH DISEASE TYPE 2U	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL RECESSIVE SPASTIC PARAPLEGIA TYPE 70	—	CTD, Disgenet, Orphanet CTD, Disgenet, Orphanet CTD, Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Charcot-Marie-Tooth disease	Uncertain significance; Benign; Likely benign; Conflicting classifications of pathogenicity	ClinVar ClinGen, ClinVar, Disgenet, GWAS catalog ClinGen, ClinVar, Disgenet, GWAS catalog ClinGen, ClinVar, Disgenet, GWAS catalog	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2U	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEJERINE-SOTTAS DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Distal spinal muscular atrophy	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Familial cancer of breast	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEREDITARY MOTOR AND SENSORY NEUROPATHIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEREDITARY MOTOR AND SENSORY NEUROPATHY, TYPES I-IV	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary spastic paraplegia	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTROPHIC NEUROPATHY OF INFANCY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTERSTITIAL LUNG AND LIVER DISEASE	—	CTD, HPO CTD, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MARS-related disorder	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MARS1-related disorder	Uncertain significance; Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERONEAL MUSCULAR ATROPHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ROUSSY-LEVY SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPASTIC PARAPLEGIA, HEREDITARY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Trichothiodystrophy 9, nonphotosensitive	Uncertain significance	ClinVar ClinVar, Disgenet, HPO ClinVar, Disgenet, HPO ClinVar, Disgenet, HPO	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
TYPE 1 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer Disease	Alzheimer disease	Pubtator	40542379	Associate	★☆☆☆☆ Found in Text Mining only
Alzheimer disease, familial, type 3	Alzheimer disease	BEFREE	27717217		★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	BEFREE	28148924		★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ataxia Telangiectasia	Ataxia Telangiectasia	BEFREE	30304680		★☆☆☆☆ Found in Text Mining only
Autosomal recessive spastic paraplegia type 70	Spastic Paraplegia	ORPHANET_DG	24482476		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Neoplasms	Breast neoplasm	Pubtator	32404475	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	28679377		★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	BEFREE	29649015		★☆☆☆☆ Found in Text Mining only
Charcot-Marie-Tooth Disease	Charcot-Marie-Tooth Disease	BEFREE	27717217, 29655802		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Charcot-Marie-Tooth Disease	Charcot-Marie-Tooth Disease	CLINVAR_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2U	Charcot-Marie-Tooth Disease	UNIPROT_DG	23729695, 24354524		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2U	Charcot-Marie-Tooth Disease	ORPHANET_DG	23729695		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2U	Charcot-Marie-Tooth Disease	BEFREE	28148924, 29582526		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2U	Charcot-Marie-Tooth Disease	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2U	Charcot-Marie-Tooth Disease	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal Carcinoma	Colorectal Cancer	BEFREE	30304680		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	23377640, 29449140, 29649015, 31383853		★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	BEFREE	28692474		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	29175219, 29449140		★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty Liver	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperlipoproteinemia Type IIa	Hyperlipoproteinemia	BEFREE	31821958		★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
INFANTILE LIVER FAILURE SYNDROME 2	Liver failure	BEFREE	30558828		★☆☆☆☆ Found in Text Mining only
INTERSTITIAL LUNG AND LIVER DISEASE	Interstitial Lung And Liver Disease	UNIPROT_DG	24103465, 25913036		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTERSTITIAL LUNG AND LIVER DISEASE	Interstitial Lung And Liver Disease	ORPHANET_DG	24103465, 25913036		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTERSTITIAL LUNG AND LIVER DISEASE	Interstitial Lung And Liver Disease	BEFREE	28148924, 29655802, 30271085		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTERSTITIAL LUNG AND LIVER DISEASE	Interstitial Lung And Liver Disease	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTERSTITIAL LUNG AND LIVER DISEASE	Interstitial Lung And Liver Disease	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Liver Failure	Liver failure	BEFREE	28248208, 28692474, 29266788		★☆☆☆☆ Found in Text Mining only
Liver Failure, Acute	Liver failure	BEFREE	28692474		★☆☆☆☆ Found in Text Mining only
Lung diseases	Lung Diseases	BEFREE	25913036		★☆☆☆☆ Found in Text Mining only
Lung Diseases, Interstitial	Lung Diseases	BEFREE	29517585		★☆☆☆☆ Found in Text Mining only
Lung Diseases, Interstitial	Lung Diseases	HPO_DG			★☆☆☆☆ Found in Text Mining only
Major Depressive Disorder	Mental Depression	BEFREE	22647524, 31383853		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	28679377		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	28679377		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	23377640, 29449140, 29649015, 31383853		★☆☆☆☆ Found in Text Mining only
Mild Mental Retardation	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	37587064	Associate	★☆☆☆☆ Found in Text Mining only
Nephrotic Syndrome	Nephrotic Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	28679377, 31637881		★☆☆☆☆ Found in Text Mining only
Pelger-Huet Anomaly	Pelger-Huet Anomaly	BEFREE	31761904		★☆☆☆☆ Found in Text Mining only
Peripheral axonal neuropathy	Peripheral axonal neuropathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Nervous System Diseases	HPO_DG			★☆☆☆☆ Found in Text Mining only
Polyneuropathies	Polyneuropathy	Pubtator	31356216	Associate	★☆☆☆☆ Found in Text Mining only
Pulmonary Alveolar Proteinosis	Alveolar proteinosis	BEFREE	25913036, 29517585, 29775242, 30723866		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Pulmonary Alveolar Proteinosis	Pulmonary alveolar proteinosis	Pubtator	30723866	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Pulmonary Alveolar Proteinosis	Alveolar proteinosis	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Pulmonary Alveolar Proteinosis	Alveolar proteinosis	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Pulmonary alveolar proteinosis congenital	Pulmonary alveolar proteinosis	Pubtator	30723866	Associate	★☆☆☆☆ Found in Text Mining only
RENAL ADYSPLASIA	Renal Aplasia	BEFREE	29606289		★☆☆☆☆ Found in Text Mining only
Steatohepatitis	Fatty Liver	HPO_DG			★☆☆☆☆ Found in Text Mining only
Subarachnoid Hemorrhage	Subarachnoid hemorrhage	BEFREE	10496256		★☆☆☆☆ Found in Text Mining only