RARS1 (arginyl-tRNA synthetase 1)

Gene

• Entrez ID: 5917
• Gene name: Arginyl-tRNA synthetase 1
• Gene symbol: RARS1
• Synonyms (NCBI Gene): ArgRS, DALRD1, HLD9, RARS
• Chromosome: 5
• Chromosome location: 5q34
• 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 prot

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs139644798	C>T	Pathogenic	Coding sequence variant, missense variant
rs180760483	C>T	Likely-pathogenic	Coding sequence variant, stop gained
rs369398935	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs672601372	A>C,G,T	Pathogenic	Coding sequence variant, missense variant
rs672601373	G>A,T	Pathogenic	Splice donor variant
rs672601374	TG>-	Pathogenic	Coding sequence variant, frameshift variant
rs672601375	A>G	Pathogenic	Initiator codon variant, missense variant
rs754997301	TG>-,TGTG	Pathogenic	Frameshift variant, coding sequence variant
rs757249400	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs768923402	TGTATTGAA>-	Likely-pathogenic	Coding sequence variant, inframe deletion
rs769713780	T>A,C,G	Pathogenic	Missense variant, initiator codon variant
rs1057518618	AAGA>-	Pathogenic	Coding sequence variant, frameshift variant
rs1064792894	TA>-	Pathogenic	Coding sequence variant, frameshift variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000049	Function	TRNA binding	IEA
GO:0000166	Function	Nucleotide binding	IEA
GO:0004812	Function	Aminoacyl-tRNA ligase activity	IEA
GO:0004814	Function	Arginine-tRNA ligase activity	IBA
GO:0004814	Function	Arginine-tRNA ligase activity	IDA	25288775
GO:0004814	Function	Arginine-tRNA ligase activity	IEA
GO:0004814	Function	Arginine-tRNA ligase activity	TAS
GO:0005515	Function	Protein binding	IPI	9556618, 16055448, 24656866, 28514442, 32296183, 33961781
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IDA	10791971
GO:0005654	Component	Nucleoplasm	IDA
GO:0005730	Component	Nucleolus	IDA
GO:0005737	Component	Cytoplasm	IDA	10791971
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	TAS	7590355
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:0006420	Process	Arginyl-tRNA aminoacylation	IBA
GO:0006420	Process	Arginyl-tRNA aminoacylation	IDA	25288775
GO:0006420	Process	Arginyl-tRNA aminoacylation	IEA
GO:0006420	Process	Arginyl-tRNA aminoacylation	TAS	7590355
GO:0016020	Component	Membrane	HDA	19946888
GO:0016874	Function	Ligase activity	IEA
GO:0017101	Component	Aminoacyl-tRNA synthetase multienzyme complex	IDA	19131329
GO:0017101	Component	Aminoacyl-tRNA synthetase multienzyme complex	IEA
GO:0034618	Function	Arginine binding	IEA
GO:0045296	Function	Cadherin binding	HDA	25468996
GO:0070062	Component	Extracellular exosome	HDA	19056867

Other IDs

• MIM: 107820
• HGNC: 9870
• e!Ensembl: ENSG00000113643

Protein

• UniProt ID: P54136
• Protein name: Arginine--tRNA ligase, cytoplasmic (EC 6.1.1.19) (Arginyl-tRNA synthetase) (ArgRS)
• Protein function: Forms part of a macromolecular complex that catalyzes the attachment of specific amino acids to cognate tRNAs during protein synthesis (PubMed:25288775). Modulates the secretion of AIMP1 and may be involved in generation of the inflammatory cyto
• PDB: 4Q2T, 4Q2X, 4Q2Y, 4R3Z, 4ZAJ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03485	Arg_tRNA_synt_N	78 → 166	Arginyl tRNA synthetase N terminal domain	Domain
  PF00750	tRNA-synt_1d	174 → 520	tRNA synthetases class I (R)	Family
  PF05746	DALR_1	534 → 660	DALR anticodon binding domain	Domain

• Sequence:

  MDVLVSECSARLLQQEEEIKSLTAEIDRLKNCGCLGASPNLEQLQEENLKLKYRLNILRK
  SLQAERNKPTKNMINIISRLQEVFGHAIKAAYPDLENPPLLVTPSQQAKFGDYQCNSAMG
  ISQMLKTKEQKVNPREIAENITKHLPDNECIEKVEIAGPGFINVHLRKDFVSEQLTSLLV
  NGVQLPALGENKKVIVDFSSPNIAKEMHVGHLRSTIIGESISRLFEFAGYDVLRLNHVGD
  WGTQFGMLIAHLQDKFPDYLTVSPPIGDLQVFYKESKKRFDTEEEFKKRAYQCVVLLQGK
  NPDITKAWKLICDVSRQELNKIYDALDVSLIERGESFYQDRMNDIVKEFEDRGFVQVDDG
  RKIVFVPGCSIPLTIVKSDGGYTYDTSDLAAIKQRLFEEKADMIIYVVDNGQSVHFQTIF
  AAAQMIGWYDPKVTRVFHAGFGVVLGEDKKKFKTRSGETVRLMDLLGEGLKRSMDKLKEK
  ERDKVLTAEELNAAQTSVAYGCIKYADLSHNRLNDYIFSFDKMLDDRGNTAAYLLYAFTR
  IRSIARLANIDEEMLQKAARETKILLDHEKEWKLGRCILRFPEILQKILDDLFLHTLCDY
  IYELATAFTEFYDSCYCVEKDRQTGKILKVNMWRMLLCEAVAAVMAKGFDILGIKPVQRM
  

• Sequence length: 660

Pathways

KEGG:

Aminoacyl-tRNA biosynthesis

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
Hypomyelinating leukodystrophy 9	Likely pathogenic; Pathogenic	rs1758704447, rs1422385923, rs672601372, rs672601373, rs672601374, rs672601375, rs369398935, rs1064792894, rs769713780, rs1358682351, rs779915495	RCV003484443 RCV001783665 RCV000149498 RCV000149499 RCV000149500 RCV000149501 RCV000149502 RCV000256225 RCV000785104 RCV005628295 RCV001255852	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Leukodystrophy	Likely pathogenic	rs779915495	RCV004798897	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
RARS1-related disorder	Likely pathogenic	rs1758706556	RCV003406235	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign; Likely benign	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
LEUKODYSTROPHY, HYPOMYELINATING, 9	—	CTD, HPO CTD, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	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
Melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pancreatic adenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
5q-syndrome	5q-syndrome	BEFREE	15725470, 17412418, 17634407		★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	BEFREE	10089900, 19074058		★☆☆☆☆ Found in Text Mining only
B-CELL MALIGNANCY, LOW-GRADE	Lymphocytic Leukemia	BEFREE	15648093		★☆☆☆☆ Found in Text Mining only
Brain atrophy	Brain atrophy	BEFREE	31814314		★☆☆☆☆ Found in Text Mining only
Brain Diseases	Brain disease	Pubtator	31814314	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	24510587		★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	GENOMICS_ENGLAND_DG	24777941		★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	BEFREE	31814314		★☆☆☆☆ Found in Text Mining only
Chronic Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	15648093		★☆☆☆☆ Found in Text Mining only
Chronic myeloproliferative disorder	Myeloproliferative disorder	BEFREE	26874914		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	32802869	Associate	★☆☆☆☆ Found in Text Mining only
Congenital chromosomal disease	Congenital Chromosomal Disease	BEFREE	9595817		★☆☆☆☆ Found in Text Mining only
Demyelinating Diseases	Demyelinating diseases	Pubtator	28905880	Associate	★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Eosinophilia	Eosinophilia	BEFREE	8251398		★☆☆☆☆ Found in Text Mining only
Epileptic encephalopathy	Epileptic encephalopathy	BEFREE	31814314		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	GENOMICS_ENGLAND_DG	24777941		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Head and Neck Carcinoma	Head And Neck Carcinoma	BEFREE	29133573		★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	GENOMICS_ENGLAND_DG	24777941		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	30500859	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Juvenile Myelomonocytic Leukemia	Myelomonocytic Leukemia	BEFREE	22195406, 23572136, 25212680		★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	BEFREE	17550846		★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	17550846		★☆☆☆☆ Found in Text Mining only
Leukemia, Myelomonocytic, Chronic	Myelomonocytic Leukemia	BEFREE	23572136		★☆☆☆☆ Found in Text Mining only
Leukodystrophy	Leukodystrophy	BEFREE	29451896, 31814314		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Leukodystrophy	Leukodystrophy	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Leukodystrophy Metachromatic	Metachromatic leukodystrophy	Pubtator	29451896	Associate	★☆☆☆☆ Found in Text Mining only
LEUKODYSTROPHY, HYPOMYELINATING, 9	Leukodystrophy	GENOMICS_ENGLAND_DG	24777941, 27564080		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEUKODYSTROPHY, HYPOMYELINATING, 9	Leukodystrophy	CLINVAR_DG	24777941, 28905880		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEUKODYSTROPHY, HYPOMYELINATING, 9	Leukodystrophy	ORPHANET_DG	24777941		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEUKODYSTROPHY, HYPOMYELINATING, 9	Leukodystrophy	UNIPROT_DG	24777941		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEUKODYSTROPHY, HYPOMYELINATING, 9	Leukodystrophy	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation	Leukoencephalopathy With Brainstem And Spinal Cord Involvement And Lactate Elevation	BEFREE	30006346		★☆☆☆☆ Found in Text Mining only
Malignant Head and Neck Neoplasm	Head and neck cancer	BEFREE	29133573		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	24510587		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	29133573		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ 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
MYELODYSPLASTIC SYNDROME	Myelodysplastic Syndrome	BEFREE	10089900, 17412418, 17550846, 17654685, 19120370, 26874914, 27655690, 7748962, 9697872		★☆☆☆☆ Found in Text Mining only
Myelodysplastic Syndrome with Isolated del(5q)	Myelodysplastic syndrome	BEFREE	15725470, 17412418, 17634407		★☆☆☆☆ Found in Text Mining only
Myelodysplastic-Myeloproliferative Diseases	Myelodysplastic-Myeloproliferative Diseases	BEFREE	25212680		★☆☆☆☆ Found in Text Mining only
Myelofibrosis	Myelofibrosis	BEFREE	19074058		★☆☆☆☆ Found in Text Mining only
Myeloproliferative disease	Myeloproliferative disorder	BEFREE	19074058, 26874914		★☆☆☆☆ Found in Text Mining only
Nasopharyngeal carcinoma	Nasopharyngeal Carcinoma	BEFREE	29133573		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	15648093, 17443684, 20864173		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	30006346		★☆☆☆☆ Found in Text Mining only
Neurodevelopmental Disorders	Neurodevelopmental Disorders	BEFREE	30006346		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	GENOMICS_ENGLAND_DG	24777941		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	BEFREE	31814314		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Nystagmus Pathologic	Nystagmus	Pubtator	31814314	Associate	★☆☆☆☆ Found in Text Mining only
Pelizaeus-Merzbacher Disease	Pelizaeus-Merzbacher disease	BEFREE	28905880		★☆☆☆☆ Found in Text Mining only
Pontocerebellar Hypoplasia Type 6	Pontoneocerebellar hypoplasia	BEFREE	30006346		★☆☆☆☆ Found in Text Mining only
Primary Myelofibrosis	Myelofibrosis	BEFREE	19074058		★☆☆☆☆ Found in Text Mining only
Pseudobulbar Palsy	Pseudobulbar Palsy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	26736064	Associate	★☆☆☆☆ Found in Text Mining only
RARS-related autosomal recessive hypomyelinating leukodystrophy	Hypomyelinating Leukodystrophy	Orphanet			★☆☆☆☆ Found in Text Mining only
Refractory anaemia with excess blasts	Myelodysplastic syndrome	BEFREE	17550846		★☆☆☆☆ Found in Text Mining only
Refractory anemia with ringed sideroblasts	Anemia With Ringed Sideroblasts	BEFREE	12165459, 18820995, 20194893, 26874914		★☆☆☆☆ Found in Text Mining only
Refractory anemias	Anemia	BEFREE	19120370, 25212680		★☆☆☆☆ Found in Text Mining only
secondary acute myeloid leukemia	Myeloid leukemia	BEFREE	17550846		★☆☆☆☆ Found in Text Mining only
Thrombocythemia, Essential	Thrombocythemia	BEFREE	19120370		★☆☆☆☆ Found in Text Mining only
Thrombocytosis	Thrombocytosis	BEFREE	18820995, 20194893		★☆☆☆☆ Found in Text Mining only
Uterine Cervical Neoplasms	Uterine neoplasm	Pubtator	21736279	Associate	★☆☆☆☆ Found in Text Mining only