DARS1 (aspartyl-tRNA synthetase 1)

Gene

• Entrez ID: 1615
• Gene name: Aspartyl-tRNA synthetase 1
• Gene symbol: DARS1
• Synonyms (NCBI Gene): DARS, HBSL, aspRS
• Chromosome: 2
• Chromosome location: 2q21.3
• Summary: This gene encodes a member of a multienzyme complex that functions in mediating the attachment of amino acids to their cognate tRNAs. The encoded protein ligates L-aspartate to tRNA(Asp). Mutations in this gene have been found in patients showing hypomyel

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs141522501	C>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs147077598	G>A,C	Pathogenic	Missense variant, coding sequence variant
rs199776135	A>C	Conflicting-interpretations-of-pathogenicity	Intron variant
rs369152939	G>A,C	Pathogenic	Coding sequence variant, missense variant
rs370064817	C>A,G,T	Pathogenic	Coding sequence variant, missense variant
rs377510027	A>G	Likely-pathogenic	Coding sequence variant, missense variant
rs527236040	T>A	Pathogenic	Coding sequence variant, missense variant
rs587776984	G>A	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs587776985	C>A,T	Pathogenic	Missense variant, coding sequence variant
rs761230959	C>G,T	Likely-pathogenic	Coding sequence variant, missense variant
rs886037635	T>G	Pathogenic	Coding sequence variant, missense variant
rs967111310	C>T	Pathogenic	Missense variant, coding sequence variant
rs1060499772	C>G	Likely-pathogenic	Missense variant, coding sequence variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0003676	Function	Nucleic acid binding	IEA
GO:0003723	Function	RNA binding	HDA	22658674
GO:0003723	Function	RNA binding	IBA
GO:0004046	Function	Aminoacylase activity	TAS	8449960
GO:0004812	Function	Aminoacyl-tRNA ligase activity	IEA
GO:0004815	Function	Aspartate-tRNA ligase activity	IBA
GO:0004815	Function	Aspartate-tRNA ligase activity	IEA
GO:0004815	Function	Aspartate-tRNA ligase activity	TAS	8449960
GO:0005515	Function	Protein binding	IPI	16189514, 17474147, 19380743, 21900206, 25416956, 25609649, 32296183
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	TAS	8449960
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:0006412	Process	Translation	TAS	8449960
GO:0006418	Process	TRNA aminoacylation for protein translation	IEA
GO:0006422	Process	Aspartyl-tRNA aminoacylation	IBA
GO:0006422	Process	Aspartyl-tRNA aminoacylation	IEA
GO:0006422	Process	Aspartyl-tRNA aminoacylation	TAS	8449960
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	19131329
GO:0017101	Component	Aminoacyl-tRNA synthetase multienzyme complex	IEA
GO:0045202	Component	Synapse	IEA
GO:0065003	Process	Protein-containing complex assembly	TAS	8449960
GO:0070062	Component	Extracellular exosome	HDA	20458337

Other IDs

• MIM: 603084
• HGNC: 2678
• e!Ensembl: ENSG00000115866

Protein

• UniProt ID: P14868
• Protein name: Aspartate--tRNA ligase, cytoplasmic (EC 6.1.1.12) (Aspartyl-tRNA synthetase) (AspRS) (Cell proliferation-inducing gene 40 protein)
• 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.
• PDB: 4J15, 5Y6L, 6IY6
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01336	tRNA_anti-codon	60 → 145	OB-fold nucleic acid binding domain	Domain
  PF00152	tRNA-synt_2	175 → 496	tRNA synthetases class II (D, K and N)	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expression in the developing and adult brain shows similar patterns. Highly expressed in the ventricular and subventricular zones, including hippocampal subfields, the midlateral temporal cortex and the frontal polar cortex. The cerebe
• Sequence:

  MPSASASRKSQEKPREIMDAAEDYAKERYGISSMIQSQEKPDRVLVRVRDLTIQKADEVV
  WVRARVHTSRAKGKQCFLVLRQQQFNVQALVAVGDHASKQMVKFAANINKESIVDVEGVV
  RKVNQKIGSCTQQDVELHVQKIYVISLAEPRLPLQLDDAVRPEAEGEEEGRATVNQDTRL
  DNRVIDLRTSTSQAVFRLQSGICHLFRETLINKGFVEIQTPKIISAASEGGANVFTVSYF
  KNNAYLAQSPQLYKQMCICADFEKVFSIGPVFRAEDSNTHRHLTEFVGLDIEMAFNYHYH
  EVMEEIADTMVQIFKGLQERFQTEIQTVNKQFPCEPFKFLEPTLRLEYCEALAMLREAGV
  EMGDEDDLSTPNEKLLGHLVKEKYDTDFYILDKYPLAVRPFYTMPDPRNPKQSNSYDMFM
  RGEEILSGAQRIHDPQLLTERALHHGIDLEKIKAYIDSFRFGAPPHAGGGIGLERVTMLF
  LGLHNVRQTSMFPRDPKRLTP

• Sequence length: 501

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
Abnormal brain morphology	Likely pathogenic	rs1060499772	RCV000454195	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypomyelination with brain stem and spinal cord involvement and leg spasticity	Pathogenic; Likely pathogenic	rs527236040, rs967111310, rs370064817, rs369152939, rs886037635, rs587776985, rs147077598	RCV000132724 RCV000625842 RCV000043682 RCV000043683 RCV000043684 RCV000043686 RCV000043687	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Cervical cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DARS1-related disorder	Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SYSTEMIC LUPUS ERYTHEMATOSUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Brain Stem Neoplasms	Brain stem neoplasms	Pubtator	23643384	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	32526457	Associate	★☆☆☆☆ Found in Text Mining only
Clumsiness - motor delay	Motor delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	37800782	Associate	★☆☆☆☆ Found in Text Mining only
Congenital microcephaly	Congenital Microcephaly	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	BEFREE	27871331		★☆☆☆☆ Found in Text Mining only
Demyelinating Diseases	Demyelinating diseases	Pubtator	25527264	Associate	★☆☆☆☆ Found in Text Mining only
Developmental regression	Developmental regression	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	GWASCAT_DG	28736931		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	35111402	Associate	★☆☆☆☆ Found in Text Mining only
Heart Septal Defects Ventricular	Congenital heart septal defect	Pubtator	27871331	Associate	★☆☆☆☆ Found in Text Mining only
Hypomyelination with brain stem and spinal cord involvement and leg spasticity	Hypomyelination With Brainstem And Spinal Cord Involvement And Leg Spasticity	BEFREE	23643384		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hypomyelination with brain stem and spinal cord involvement and leg spasticity	Hypomyelination With Brainstem And Spinal Cord Involvement And Leg Spasticity	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
HYPOMYELINATION WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LEG SPASTICITY	Hypomyelination With Brainstem And Spinal Cord Involvement And Leg Spasticity	GENOMICS_ENGLAND_DG	23643384, 24357685, 25527264		★☆☆☆☆ Found in Text Mining only
HYPOMYELINATION WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LEG SPASTICITY	Hypomyelination With Brainstem And Spinal Cord Involvement And Leg Spasticity	UNIPROT_DG	23643384		★☆☆☆☆ Found in Text Mining only
HYPOMYELINATION WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LEG SPASTICITY	Hypomyelination With Brainstem And Spinal Cord Involvement And Leg Spasticity	ORPHANET_DG	23643384		★☆☆☆☆ Found in Text Mining only
HYPOMYELINATION WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LEG SPASTICITY	Hypomyelination With Brainstem And Spinal Cord Involvement And Leg Spasticity	BEFREE	25527264, 27816769, 29615866		★☆☆☆☆ Found in Text Mining only
HYPOMYELINATION WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LEG SPASTICITY	Hypomyelination With Brainstem And Spinal Cord Involvement And Leg Spasticity	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
HYPOMYELINATION WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LEG SPASTICITY	Hypomyelination With Brainstem And Spinal Cord Involvement And Leg Spasticity	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	35638109	Associate	★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	29615866		★☆☆☆☆ Found in Text Mining only
Leukodystrophy	Leukodystrophy	BEFREE	27816769, 29615866		★☆☆☆☆ Found in Text Mining only
Leukodystrophy	Leukodystrophy	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Leukoencephalopathy	Leukoencephalopathy	BEFREE	21121901, 25527264, 26620921		★☆☆☆☆ Found in Text Mining only
Leukoencephalopathy	Leukoencephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation	Leukoencephalopathy With Brainstem And Spinal Cord Involvement And Lactate Elevation	BEFREE	22422207, 30006346		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Systemic	Lupus Erythematosus	GWASCAT_DG	28714469		★☆☆☆☆ Found in Text Mining only
nervous system disorder	Nervous System Disorder	BEFREE	27699474		★☆☆☆☆ 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	HPO_DG			★☆☆☆☆ Found in Text Mining only
Paraplegia	Paraplegia	Pubtator	25527264	Associate	★☆☆☆☆ Found in Text Mining only
Pontocerebellar Hypoplasia Type 6	Pontoneocerebellar hypoplasia	BEFREE	30006346		★☆☆☆☆ Found in Text Mining only
Uterine Cervical Neoplasms	Uterine neoplasm	Pubtator	35638109	Associate	★☆☆☆☆ Found in Text Mining only
Ventricular Septal Defects	Ventricular septal defect	BEFREE	27871331		★☆☆☆☆ Found in Text Mining only