DARS1 (aspartyl-tRNA synthetase 1)

Gene

• Entrez ID: 1615
• Gene name: Aspartyl-tRNA synthetase 1
• Gene symbol: DARS1
• Synonyms: 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:0003723	Function	RNA binding	HDA	22658674
GO:0003723	Function	RNA binding	IBA	21873635
GO:0004046	Function	Aminoacylase activity	TAS	8449960
GO:0004815	Function	Aspartate-tRNA ligase activity	IBA	21873635
GO:0005515	Function	Protein binding	IPI	16189514, 17474147, 19380743, 21900206, 25416956, 25609649, 32296183
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	TAS	8449960
GO:0005829	Component	Cytosol	IBA	21873635
GO:0005829	Component	Cytosol	IDA	19289464
GO:0005829	Component	Cytosol	TAS
GO:0006412	Process	Translation	TAS	8449960
GO:0006418	Process	TRNA aminoacylation for protein translation	TAS
GO:0006422	Process	Aspartyl-tRNA aminoacylation	IBA	21873635
GO:0016020	Component	Membrane	HDA	19946888
GO:0017101	Component	Aminoacyl-tRNA synthetase multienzyme complex	IBA	21873635
GO:0017101	Component	Aminoacyl-tRNA synthetase multienzyme complex	IDA	19131329
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

• Sequence:

  MPSASASRKSQEKPREIMDAAEDYAKERYGISSMIQSQEKPDRVLVRVRDLTIQKADEVV
  WVRARVHTSRAKGKQCFLVLRQQQFNVQALVAVGDHASKQMVKFAANINKESIVDVEGVV
  RKVNQKIGSCTQQDVELHVQKIYVISLAEPRLPLQLDDAVRPEAEGEEEGRATVNQDTRL
  DNRVIDLRTSTSQAVFRLQSGICHLFRETLINKGFVEIQTPKIISAASEGGANVFTVSYF
  KNNAYLAQSPQLYKQMCICADFEKVFSIGPVFRAEDSNTHRHLTEFVGLDIEMAFNYHYH
  EVMEEIADTMVQIFKGLQERFQTEIQTVNKQFPCEPFKFLEPTLRLEYCEALAMLREAGV
  EMGDEDDLSTPNEKLLGHLVKEKYDTDFYILDKYPLAVRPFYTMPDPRNPKQSNSYDMFM
  RGEEILSGAQRIHDPQLLTERALHHGIDLEKIKAYIDSFRFGAPPHAGGGIGLERVTMLF
  LGLHNVRQTSMFPRDPKRLTP

• Sequence length: 501

Pathways

KEGG:

Aminoacyl-tRNA biosynthesis

Reactome:

Cytosolic tRNA aminoacylation

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Developmental regression	Developmental regression	rs1224421127
Diabetes mellitus	Diabetes Mellitus, Non-Insulin-Dependent	rs587776515, rs61730328, rs606231121, rs606231122, rs79020217, rs77625743, rs78378398, rs606231123, rs4402960, rs1362648752, rs3745368, rs3792267, rs3842570, rs5030952, rs2975760, rs119489103, rs7903146, rs12255372, rs11196205, rs104893649, rs80356624, rs80356616, rs80356625, rs80356611, rs104894237, rs80356613, rs137852740, rs137852786, rs387906407, rs151344623, rs28938469, rs28936371, rs137852672, rs80356637, rs80356642, rs80356653, rs137852673, rs137852674, rs80356634, rs80356651, rs193929360, rs137853334, rs137853335, rs137853336, rs1600731198, rs137853338, rs121964882, rs121964883, rs387906511, rs121964884, rs121964885, rs2147483647, rs387906512, rs121964887, rs121964888, rs121964889, rs121964890, rs121964891, rs28934878, rs74315383, rs121964893, rs886037620, rs886037621, rs80356663, rs121434593, rs121913150, rs587776825, rs137853236, rs2135842335, rs137853237, rs137853238, rs2135818776, rs1566092470, rs1463923467, rs137853243, rs137853244, rs2135839114, rs137853245, rs2135847417, rs121918407, rs104894005, rs104894006, rs80356655, rs104894008, rs104894009, rs104894010, rs104894011, rs80356654, rs104894016, rs193929376, rs193929374, rs193929375, rs193929373, rs80356666, rs80356669, rs80356664, rs193929366, rs1048095, rs193929355, rs193929356, rs1259467443, rs104893642, rs387906777, rs387906779, rs141804752, rs182349376, rs184917682, rs193922396, rs193922400, rs193922401, rs137852676, rs193922407, rs193922638, rs193922257, rs193922258, rs193922259, rs193922260, rs193922261, rs193922262, rs193922263, rs193922264, rs193922265, rs193922268, rs193921338, rs193922269, rs193922272, rs193922273, rs193922275, rs193922278, rs193922279, rs193922280, rs193922281, rs193922282, rs193922283, rs193922284, rs193922286, rs193922287, rs193922289, rs193922291, rs193922295, rs193922297, rs193922300, rs193922302, rs193922303, rs193922308, rs193922313, rs193922314, rs144723656, rs193922315, rs193922316, rs193922317, rs148311934, rs193922319, rs193922320, rs193922326, rs193922329, rs193922330, rs193922331, rs193922335, rs193922336, rs193922338, rs193922340, rs193922341, rs193922471, rs193922475, rs193922476, rs193922479, rs193922355, rs193922356, rs193922576, rs193922578, rs193922582, rs193922588, rs193922592, rs193922594, rs193922596, rs386134267, rs193922598, rs193922599, rs193922600, rs193922604, rs193922605, rs397514580, rs397515519, rs267601516, rs587780343, rs587780345, rs587780346, rs587780347, rs587780357, rs148954387, rs61736969, rs587783673, rs587783672, rs587783669, rs786204676, rs794727236, rs151344624, rs794727775, rs794727839, rs199946797, rs869320673, rs796065047, rs759072800, rs797045595, rs797045209, rs797045207, rs797045213, rs797045623, rs863225280, rs149703259, rs864321656, rs139964066, rs777870079, rs878853246, rs769268803, rs886039380, rs886041392, rs886041391, rs886042610, rs143064649, rs1057516192, rs746480424, rs1057516281, rs576684889, rs754728827, rs1057520291, rs1057520779, rs893256143, rs1057520504, rs1057524790, rs1057524902, rs1057524904, rs1057524905, rs764232985, rs1064793998, rs1064794268, rs769086289, rs369429452, rs1085307913, rs1131691416, rs765432081, rs1131692182, rs748749585, rs1554335441, rs762263694, rs1312678560, rs767565869, rs1375656631, rs1554335391, rs1360415315, rs1554335616, rs1554335752, rs1554909277, rs769518471, rs757171524, rs768951263, rs762703502, rs1555212248, rs1555212359, rs1555813319, rs1555816654, rs1553638903, rs1553638909, rs948820149, rs371977235, rs1553784995, rs76474829, rs200998587, rs1415041911, rs1554334894, rs1260178539, rs1554335421, rs1555211904, rs779184183, rs1554335564, rs200670692, rs1400535021, rs1554334872, rs1555212749, rs1553876668, rs1553878211, rs954727530, rs1554924035, rs372307320, rs925231098, rs1554913069, rs1554933565, rs766431403, rs746714109, rs751279984, rs770664202, rs1008906426, rs758844607, rs1554924540, rs1566092307, rs753998395, rs1565885935, rs1167124132, rs1376796469, rs556436603, rs1562715657, rs1486280029, rs1564869850, rs755259997, rs769569410, rs1172328722, rs1286294151, rs1375557127, rs1568731279, rs1562715426, rs556581174, rs1564865302, rs1565886545, rs776793516, rs1568724014, rs1392795567, rs781260712, rs1562719705, rs1382448285, rs1564977373, rs750586210, rs1598842892, rs1583592247, rs780612692, rs1593060859, rs1476637197, rs751279776, rs1593060890, rs1191912908, rs1167675604, rs1583601110, rs1593058932, rs778611627, rs753296261	28736931
Hypomyelination with brainstem and spinal cord involvement and leg spasticity	HYPOMYELINATION WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LEG SPASTICITY, Hypomyelination with brain stem and spinal cord involvement and leg spasticity	rs370064817, rs369152939, rs886037635, rs587776985, rs147077598, rs527236040, rs967111310	25527264, 24357685, 23643384
Leukodystrophy	Leukodystrophy	rs74315475, rs72466451, rs267608671, rs181087667, rs267608682, rs267608674, rs587778271, rs148932047, rs886037931, rs368905417, rs768180196, rs1558211070, rs1558209947, rs1558210191, rs1280845604, rs1382083552, rs1576101665, rs1576080546, rs1576074651, rs1367958450, rs932183417
Leukoencephalopathy	Leukoencephalopathy	rs34757931
Nystagmus	Nystagmus	rs137852207, rs137852208, rs1928435502, rs137852209, rs137852210, rs1929191668, rs137852211, rs137852212, rs2124209414, rs387906720, rs387906721, rs1602791884, rs786205896

Unknown
Disease name	Disease term	dbSNP ID	References
Congenital microcephaly	Congenital microcephaly
Hypoplasia of corpus callosum	Hypoplasia of corpus callosum
Lupus erythematosus	Lupus Erythematosus, Systemic		28714469
Motor delay	Clumsiness - motor delay