NARS1 (asparaginyl-tRNA synthetase 1)

Gene

• Entrez ID: 4677
• Gene name: Asparaginyl-tRNA synthetase 1
• Gene symbol: NARS1
• Synonyms (NCBI Gene): ASNRS, NARS, NEDMILEG, NEDMILG
• Chromosome: 18
• Chromosome location: 18q21.31
• Summary: Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. Asparaginyl-tRNA synthetase is localized to the cytoplasm and belongs to the class II family of tRNA synthetases. The N-terminal domain represents the si

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0003676	Function	Nucleic acid binding	IEA
GO:0004812	Function	Aminoacyl-tRNA ligase activity	IEA
GO:0004816	Function	Asparagine-tRNA ligase activity	IBA
GO:0004816	Function	Asparagine-tRNA ligase activity	IEA
GO:0004816	Function	Asparagine-tRNA ligase activity	IMP	9421509, 32738225
GO:0004816	Function	Asparagine-tRNA ligase activity	TAS	9421509
GO:0005515	Function	Protein binding	IPI	16713569, 32814053
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	TAS	9421509
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	TAS
GO:0006421	Process	Asparaginyl-tRNA aminoacylation	IBA
GO:0006421	Process	Asparaginyl-tRNA aminoacylation	IDA	9421509
GO:0006421	Process	Asparaginyl-tRNA aminoacylation	IEA
GO:0016477	Process	Cell migration	IDA	9421509
GO:0016874	Function	Ligase activity	IEA
GO:0021987	Process	Cerebral cortex development	IMP	32788587
GO:0031728	Function	CCR3 chemokine receptor binding	IDA	30171954
GO:0046983	Function	Protein dimerization activity	IDA	9421509
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145

Other IDs

• MIM: 108410
• HGNC: 7643
• e!Ensembl: ENSG00000134440

Protein

• UniProt ID: O43776
• Protein name: Asparagine--tRNA ligase, cytoplasmic (EC 6.1.1.22) (Asparaginyl-tRNA synthetase) (AsnRS) (Asparaginyl-tRNA synthetase 1)
• Protein function: Catalyzes the attachment of asparagine to tRNA(Asn) in a two-step reaction: asparagine is first activated by ATP to form Asn-AMP and then transferred to the acceptor end of tRNA(Asn) (PubMed:32738225, PubMed:32788587, PubMed:9421509). In additio
• PDB: 4ZYA, 5XIX, 8H53, 8TC7, 8TC8, 8TC9
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01336	tRNA_anti-codon	128 → 208	OB-fold nucleic acid binding domain	Domain
  PF00152	tRNA-synt_2	225 → 543	tRNA synthetases class II (D, K and N)	Domain

• Sequence:

  MVLAELYVSDREGSDATGDGTKEKPFKTGLKALMTVGKEPFPTIYVDSQKENERWNVISK
  SQLKNIKKMWHREQMKSESREKKEAEDSLRREKNLEEAKKITIKNDPSLPEPKCVKIGAL
  EGYRGQRVKVFGWVHRLRRQGKNLMFLVLRDGTGYLQCVLADELCQCYNGVLLSTESSVA
  VYGMLNLTPKGKQAPGGHELSCDFWELIGLAPAGGADNLINEESDVDVQLNNRHMMIRGE
  NMSKILKARSMVTRCFRDHFFDRGYYEVTPPTLVQTQVEGGATLFKLDYFGEEAFLTQSS
  QLYLETCLPALGDVFCIAQSYRAEQSRTRRHLAEYTHVEAECPFLTFDDLLNRLEDLVCD
  VVDRILKSPAGSIVHELNPNFQPPKRPFKRMNYSDAIVWLKEHDVKKEDGTFYEFGEDIP
  EAPERLMTDTINEPILLCRFPVEIKSFYMQRCPEDSRLTESVDVLMPNVGEIVGGSMRIF
  DSEEILAGYKREGIDPTPYYWYTDQRKYGTCPHGGYGLGLERFLTWILNRYHIRDVCLYP
  RFVQRCTP

• Sequence length: 548

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
Developmental disorder	Pathogenic	rs2051507892	RCV003127739	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mitochondrial complex 1 deficiency, nuclear type 35	Pathogenic	rs1908000576	RCV001255189	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
NARS1-related disorder	Pathogenic	rs2511576695	RCV003933857	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurodevelopmental disorder	Pathogenic	rs2051507892	RCV001262349	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities	Likely pathogenic; Pathogenic	rs778244918, rs976688001, rs747737475, rs2122431077, rs1908005677, rs2051507892, rs1908000933, rs770931044, rs148893823	RCV002052436 RCV002052437 RCV002274299 RCV002274483 RCV002274484 RCV002274170 RCV001267635 RCV001267637 RCV001267640	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities	Likely pathogenic; Pathogenic	rs2122429938, rs2051507892	RCV001391245 RCV001267639	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
DEVELOPMENTAL DISABILITIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 35	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Ataxia	Ataxia	Pubtator	32738225	Associate	★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune Diseases	BEFREE	30171954		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	24204606		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	24204606	Associate	★☆☆☆☆ Found in Text Mining only
Deafness	Deafness	Pubtator	36252909	Associate	★☆☆☆☆ Found in Text Mining only
Hypersensitivity Delayed	Hypersensitivity	Pubtator	32738225, 32788587	Associate	★☆☆☆☆ Found in Text Mining only
Lung Diseases, Interstitial	Lung Diseases	BEFREE	30171954		★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	27161446	Associate	★☆☆☆☆ Found in Text Mining only
Malnutrition	Malnutrition	BEFREE	29216957, 29544497, 31227778		★☆☆☆☆ Found in Text Mining only
Meningomyelocele	Meningomyelocele	BEFREE	31012779		★☆☆☆☆ Found in Text Mining only
Metabolic Syndrome X	Metabolic Syndrome	BEFREE	31625057		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	32738225, 32788587	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Myopathies	Mitochondrial myopathy	Pubtator	36252909	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	37587064	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	31625057		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	36252909	Associate	★☆☆☆☆ Found in Text Mining only
Oral Mucositis	Oral Mucositis	BEFREE	31092370		★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Peripheral nervous system disease	Pubtator	32738225	Associate	★☆☆☆☆ Found in Text Mining only
Post-Traumatic Stress Disorder	Stress Disorder	BEFREE	29406451		★☆☆☆☆ Found in Text Mining only
Rectal Carcinoma	Rectal Carcinoma	BEFREE	31625057		★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	32738225	Associate	★☆☆☆☆ Found in Text Mining only
Stomatitis	Stomatitis	BEFREE	31092370		★☆☆☆☆ Found in Text Mining only