LARS1 (leucyl-tRNA synthetase 1)

Gene

• Entrez ID: 51520
• Gene name: Leucyl-tRNA synthetase 1
• Gene symbol: LARS1
• Synonyms: HSPC192, ILFS1, LARS, LEURS, LEUS, LFIS, LRS, PIG44, RNTLS, cLRS, hr025Cl
• Chromosome: 5
• Chromosome location: 5q32
• Summary: This gene encodes a cytosolic leucine-tRNA synthetase, a member of the class I aminoacyl-tRNA synthetase family. The encoded enzyme catalyzes the ATP-dependent ligation of L-leucine to tRNA(Leu). It is found in the cytoplasm as part of a multisynthetase c

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs139648263	G>A	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs201861847	T>C	Pathogenic	Missense variant, coding sequence variant
rs369437593	G>A,C,T	Likely-pathogenic	Missense variant, coding sequence variant, synonymous variant, stop gained
rs757195926	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs863224047	AAATA>-	Pathogenic	Coding sequence variant, frameshift variant, 5 prime UTR variant
rs863224048	TC>-	Pathogenic	Coding sequence variant, intron variant, frameshift variant, 5 prime UTR variant
rs1057523128	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1057523129	C>G	Likely-pathogenic	Missense variant, coding sequence variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002161	Function	Aminoacyl-tRNA editing activity	IEA
GO:0004819	Function	Glutamine-tRNA ligase activity	IDA	26869582
GO:0004823	Function	Leucine-tRNA ligase activity	IBA	21873635
GO:0004823	Function	Leucine-tRNA ligase activity	TAS
GO:0005096	Function	GTPase activator activity	IMP	22424946
GO:0005515	Function	Protein binding	IPI	16055448, 22424946, 28514442
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	IDA	22424946
GO:0005764	Component	Lysosome	IMP	22424946
GO:0005783	Component	Endoplasmic reticulum	IDA	22424946
GO:0005829	Component	Cytosol	IDA	19289464
GO:0005829	Component	Cytosol	TAS
GO:0006418	Process	TRNA aminoacylation for protein translation	TAS
GO:0006425	Process	Glutaminyl-tRNA aminoacylation	IDA	26869582
GO:0006429	Process	Leucyl-tRNA aminoacylation	IBA	21873635
GO:0008361	Process	Regulation of cell size	IMP	22424946
GO:0012505	Component	Endomembrane system	IDA	22424946
GO:0016604	Component	Nuclear body	IDA
GO:0017101	Component	Aminoacyl-tRNA synthetase multienzyme complex	IDA	19131329
GO:0032008	Process	Positive regulation of TOR signaling	IMP	22424946
GO:0034198	Process	Cellular response to amino acid starvation	IMP	22424946
GO:0043547	Process	Positive regulation of GTPase activity	IMP	22424946
GO:0071230	Process	Cellular response to amino acid stimulus	IMP	22424946
GO:0071233	Process	Cellular response to leucine	IMP	22424946
GO:0106074	Process	Aminoacyl-tRNA metabolism involved in translational fidelity	IEA
GO:1904263	Process	Positive regulation of TORC1 signaling	IMP	22424946
GO:1990253	Process	Cellular response to leucine starvation	IMP	22424946

Other IDs

• MIM: 151350
• HGNC: 6512
• e!Ensembl: ENSG00000133706

Protein

• UniProt ID: Q9P2J5
• Protein name: Leucine--tRNA ligase, cytoplasmic (EC 6.1.1.4) (Leucyl-tRNA synthetase) (LeuRS) (cLRS)
• Protein function: Aminoacyl-tRNA synthetase that catalyzes the specific attachment of leucine to its cognate tRNA (tRNA(Leu)) (PubMed:25051973, PubMed:32232361). It performs tRNA aminoacylation in a two-step reaction: Leu is initially activated by ATP to form a l
• PDB: 2WFD, 6KID, 6KIE, 6KQY, 6KR7, 6LPF, 6LR6
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00133	tRNA-synt_1	19 → 110	tRNA synthetases class I (I, L, M and V)	Family
  PF00133	tRNA-synt_1	164 → 756	tRNA synthetases class I (I, L, M and V)	Family
  PF08264	Anticodon_1	794 → 928	Anticodon-binding domain of tRNA ligase	Domain

• Sequence:

  MAERKGTAKVDFLKKIEKEIQQKWDTERVFEVNASNLEKQTSKGKYFVTFPYPYMNGRLH
  LGHTFSLSKCEFAVGYQRLKGKCCLFPFGLHCTGMPIKACADKLKREIELYGCPPDFPDE
  EEEEEETSVKTEDIIIKDKAKGKKSKAAAKAGSSKYQWGIMKSLGLSDEEIVKFSEAEHW
  LDYFPPLAIQDLKRMGLKVDWRRSFITTDVNPYYDSFVRWQFLTLRERNKIKFGKRYTIY
  SPKDGQPCMDHDRQTGEGVGPQEYTLLKLKVLEPYPSKLSGLKGKNIFLVAATLRPETMF
  GQTNCWVRPDMKYIGFETVNGDIFICTQKAARNMSYQGFTKDNGVVPVVKELMGEEILGA
  SLSAPLTSYKVIYVLPMLTIKEDKGTGVVTSVPSDSPDDIAALRDLKKKQALRAKYGIRD
  DMVLPFEPVPVIEIPGFGNLSAVTICDELKIQSQNDREKLAEAKEKIYLKGFYEGIMLVD
  GFKGQKVQDVKKTIQKKMIDAGDALIYMEPEKQVMSRSSDECVVALCDQWYLDYGEENWK
  KQTSQCLKNLETFCEETRRNFEATLGWLQEHACSRTYGLGTHLPWDEQWLIESLSDSTIY
  MAFYTVAHLLQGGNLHGQAESPLGIRPQQMTKEVWDYVFFKEAPFPKTQIAKEKLDQLKQ
  EFEFWYPVDLRVSGKDLVPNHLSYYLYNHVAMWPEQSDKWPTAVRANGHLLLNSEKMSKS
  TGNFLTLTQAIDKFSADGMRLALADAGDTVEDANFVEAMADAGILRLYTWVEWVKEMVAN
  WDSLRSGPASTFNDRVFASELNAGIIKTDQNYEKMMFKEALKTGFFEFQAAKDKYRELAV
  EGMHRELVFRFIEVQTLLLAPFCPHLCEHIWTLLGKPDSIMNASWPVAGPVNEVLIHSSQ
  YLMEVTHDLRLRLKNYMMPAKGKKTDKQPLQKPSHCTIYVAKNYPPWQHTTLSVLRKHFE
  ANNGKLPDNKVIASELGSMPELKKYMKKVMPFVAMIKENLEKMGPRILDLQLEFDEKAVL
  MENIVYLTNSLELEHIEVKFASEAEDKIREDCCPGKPLNVFRIEPGVSVSLVNPQPSNGH
  FSTKIEIRQGDNCDSIIRRLMKMNRGIKDLSKVKLMRFDDPLLGPRRVPVLGKEYTEKTP
  ISEHAVFNVDLMSKKIHLTENGIRVDIGDTIIYLVH

• Sequence length: 1176

Pathways

KEGG:

Aminoacyl-tRNA biosynthesis

Reactome:

Cytosolic tRNA aminoacylation

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Alzheimer disease	Alzheimer`s Disease	rs63750215, rs28936379, rs63749851, rs63749884, rs28936380, rs63750048, rs63750579, rs63750264, rs63749964, rs63750671, rs281865161, rs63750066, rs63750399, rs63750734, rs63751039, rs63750973, rs63749810, rs63750643, rs193922916, rs63750306, rs63750590, rs63750526, rs63751235, rs661, rs63751037, rs63749885, rs63750231, rs63751229, rs63751272, rs63751223, rs63750391, rs63751163, rs281875357, rs63751141, rs63750082, rs121917807, rs63751399, rs63750265, rs63751144, rs63750886, rs63751068, rs121917808, rs63749891, rs63750083, rs63749824, rs63750577, rs267606983, rs63750218, rs63751287, rs63750900, rs145518263, rs63751475, rs63750450, rs63749805, rs63751278, rs63751106, rs63750004, rs63749806, rs63751024, rs63750248, rs63750779, rs63751139, rs63750219, rs63750298, rs63750687, rs63750851, rs1553268799, rs1561901881, rs1561905293, rs866101707, rs1566638673, rs63750009, rs1566656702, rs1566657804, rs1567885728, rs1568339995, rs1566630791, rs1555358260, rs63750964, rs1594998354, rs63751316	26830138
Anemia	Anemia, Anemia, Macrocytic	rs118204044, rs118204045, rs118204046, rs121918330, rs869320719, rs869312029, rs121918332, rs869320724, rs767094129, rs786205058, rs786205059, rs137853119, rs137853120, rs137853121, rs1384933966, rs137853122, rs137853123, rs786205060, rs267607121, rs121908584, rs80338697, rs80338699, rs120074166, rs120074167, rs1050828, rs74575103, rs137852314, rs5030868, rs137852316, rs137852317, rs137852318, rs137852319, rs137852320, rs137852321, rs137852322, rs137852323, rs137852324, rs72554665, rs387906468, rs5030872, rs137852326, rs137852333, rs137852327, rs137852328, rs137852329, rs137852330, rs137852331, rs137852332, rs137852334, rs137852335, rs137852336, rs137852339, rs76645461, rs137852340, rs137852341, rs78478128, rs137852343, rs137852344, rs137852345, rs587776730, rs137852346, rs137852347, rs137852349, rs2070404412, rs2070350038, rs2070350009, rs137852303, rs137852304, rs33946267, rs34378160, rs33933298, rs11549407, rs35724775, rs34598529, rs41469945, rs267607201, rs80338694, rs80338696, rs387907018, rs398123546, rs78365220, rs587777100, rs587777101, rs483352840, rs869312752, rs765487627, rs1557229599, rs1557230040, rs1555524842, rs782090947, rs1358275550, rs1557229736, rs1557230573, rs1556323334, rs1233124208, rs1293528130, rs146864395, rs1595503440, rs1603411214, rs137852325, rs1575247302, rs1603411177, rs1336651679, rs782322505
Developmental delay	Global developmental delay	rs28941770, rs199469464, rs281865469, rs143747297, rs398123009, rs587777428, rs786205133, rs606231459, rs797044854, rs797045027, rs864309504, rs878853160, rs886039902, rs886042046, rs886041291, rs886041382, rs1057518991, rs1057518699, rs753254213, rs748294403, rs762552974, rs1135401795, rs1553121073, rs1553122926, rs1364690005, rs1554086554, rs1554210415, rs1554168326, rs1554776342, rs1553873247, rs1567860112, rs779009256, rs1557447255, rs1564568350, rs780011005, rs1597464953, rs1200336864, rs1569513017, rs1587459606, rs1570332505, rs748888652, rs1575155995, rs2087029320, rs1589669105, rs1601769604, rs1184981709, rs749201074
Leukemia	Leukemia, Myelocytic, Acute	rs121909646, rs121913488, rs587776834, rs752746786, rs869312821, rs767454740, rs1554564297, rs11978267, rs4132601	27903959
Liver failure	Liver Failure, Acute, INFANTILE LIVER FAILURE SYNDROME 1	rs118203990, rs118203991, rs118203992, rs387907022, rs201861847, rs796065037, rs759315662, rs368196005, rs796052121, rs369437593, rs367683258, rs766314948, rs368085185, rs770446752, rs753039116, rs776797592, rs1490906786, rs1562849964, rs759960319, rs776597537, rs375350359, rs1573008071, rs1601977105, rs1174791046, rs1019313682	22607940
Microcephaly	Microcephaly	rs397704721, rs267607176, rs267607177, rs397704725, rs267606717, rs267606718, rs199422202, rs121434311, rs199422203, rs199422126, rs387906274, rs121434305, rs199422125, rs199422135, rs189678019, rs199422184, rs137852994, rs137852995, rs137852996, rs137852997, rs145489194, rs80338860, rs137852494, rs121918609, rs199422207, rs199422206, rs29001566, rs864321658, rs199422138, rs199422139, rs199422141, rs199422144, rs199422147, rs199422151, rs199422152, rs199422153, rs199422157, rs199422159, rs199422160, rs199422161, rs140602858, rs199422164, rs199422165, rs148294838, rs199422134, rs199422168, rs199422172, rs199422173, rs199422131, rs199422177, rs199422180, rs199422185, rs199422186, rs199422187, rs143931757, rs199422189, rs199422192, rs199422194, rs199422195, rs199422196, rs199422197, rs199422199, rs753597039, rs1488084787, rs387906961, rs755862917, rs387907082, rs587776899, rs387907083, rs587776900, rs587776901, rs387907084, rs863223322, rs764201220, rs202247811, rs763915472, rs587776986, rs587777036, rs398122971, rs374351172, rs373278668, rs398122976, rs121909123, rs587783393, rs730882076, rs587783211, rs144716013, rs606231255, rs587783215, rs587783216, rs587783220, rs587783221, rs587783225, rs587783227, rs587783228, rs587783230, rs587783238, rs587783239, rs587783240, rs587783245, rs587783247, rs587783248, rs587783258, rs587783259, rs587783263, rs587783265, rs587783268, rs587783269, rs587783272, rs587783275, rs587783277, rs587783278, rs587783280, rs587783282, rs587783283, rs587783285, rs587783287, rs587783288, rs587783289, rs587783292, rs587783295, rs587784452, rs587783741, rs587783735, rs587783392, rs587783390, rs587783387, rs587783410, rs202058504, rs587783423, rs587783421, rs587783414, rs587784553, rs587784558, rs587784546, rs587784549, rs587784554, rs587784412, rs876661307, rs869025200, rs747831095, rs748529285, rs797045316, rs797045315, rs797045314, rs759632528, rs797045313, rs797045311, rs754282058, rs797045441, rs797045454, rs797045430, rs869312853, rs797046109, rs767399782, rs863225127, rs863225464, rs863225465, rs780270096, rs864321621, rs864321620, rs775277800, rs879253817, rs869312824, rs761447719, rs753406334, rs147622433, rs199422137, rs879255522, rs879255524, rs879255523, rs886037892, rs886037893, rs886037894, rs886037895, rs199422169, rs886041709, rs886041282, rs138228629, rs759188041, rs769688376, rs1057517688, rs1057519087, rs1057518268, rs933106143, rs201362977, rs754909135, rs1057520873, rs1060499758, rs1060499757, rs199422146, rs748016594, rs1085307120, rs763715733, rs1064795945, rs763800571, rs1554728351, rs1553227021, rs555866170, rs1553895368, rs1334947797, rs769818500, rs1321892596, rs1553227645, rs1404276011, rs1553228275, rs1554471681, rs1554496609, rs1555420891, rs1555418825, rs587784548, rs1555723585, rs199736219, rs745997770, rs765275884, rs1553924800, rs1554730137, rs1229568621, rs1482100822, rs979186313, rs758157294, rs1555294652, rs1555299107, rs1553264033, rs1553259539, rs1553254322, rs1553259528, rs981349334, rs1553264036, rs1553253022, rs754267846, rs776034810, rs1342429887, rs752140135, rs1006898944, rs571640983, rs1477524771, rs763909256, rs199910503, rs1553223496, rs759663956, rs1553446603, rs1555139372, rs1555143325, rs1350194762, rs1555141158, rs1553225179, rs769481947, rs769364943, rs748011724, rs1334301723, rs746341112, rs149225624, rs765113367, rs1567024512, rs142865061, rs772050241, rs201721894, rs1557966012, rs1379578836, rs1568334868, rs1185537869, rs1602333390, rs1163303148, rs774338373, rs770540184, rs1571600045, rs1571601267, rs1571602991, rs1588472215, rs1599841026, rs1558328287, rs1571600860, rs1571596976, rs1309880692, rs1435239428, rs1588634016, rs1751797979, rs1810830776, rs1815354949, rs1949984655, rs886039658, rs1943461045, rs777711720, rs2031759596, rs1555710223, rs1221031683, rs774069989, rs2058919680, rs1170413397, rs1213710245, rs1599851667, rs1599760058, rs1971033478, rs746967357

Unknown
Disease name	Disease term	dbSNP ID	References
Blood coagulation disorders	Blood Coagulation Disorders
Fatty liver	Fatty Liver, Steatohepatitis
Liver failure-multisystemic involvement syndrome	Acute infantile liver failure-multisystemic involvement syndrome