IARS2 (isoleucyl-tRNA synthetase 2, mitochondrial)

Gene

• Entrez ID: 55699
• Gene name: Isoleucyl-tRNA synthetase 2, mitochondrial
• Gene symbol: IARS2
• Synonyms: CAGSSS, ILERS
• Chromosome: 1
• Chromosome location: 1q41
• 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
rs143722284	G>A	Pathogenic, likely-benign	Coding sequence variant, missense variant
rs146618526	G>A,T	Pathogenic	Missense variant, coding sequence variant
rs151241066	G>A	Pathogenic	Missense variant, coding sequence variant
rs373436822	G>A	Pathogenic, uncertain-significance	Coding sequence variant, stop gained
rs587783070	C>T	Pathogenic	Coding sequence variant, missense variant
rs773732328	C>A,G,T	Likely-pathogenic	Coding sequence variant, synonymous variant, stop gained, missense variant
rs1287308680	C>A,T	Likely-pathogenic	Stop gained, coding sequence variant, missense variant
rs1571845061	T>C	Pathogenic	Coding sequence variant, missense variant
rs1571863769	A>G	Pathogenic	Coding sequence variant, missense variant
rs1571865562	C>T	Pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT052088	hsa-let-7b-5p	CLASH	23622248
MIRT049747	hsa-miR-92a-3p	CLASH	23622248
MIRT048072	hsa-miR-197-3p	CLASH	23622248
MIRT040636	hsa-miR-92b-3p	CLASH	23622248
MIRT1058046	hsa-miR-3180-5p	CLIP-seq
MIRT1058047	hsa-miR-376a	CLIP-seq
MIRT1058048	hsa-miR-376b	CLIP-seq
MIRT1058049	hsa-miR-487a	CLIP-seq
MIRT1058050	hsa-miR-520a-5p	CLIP-seq
MIRT1058051	hsa-miR-525-5p	CLIP-seq
MIRT1058052	hsa-miR-532-5p	CLIP-seq
MIRT2013337	hsa-miR-1278	CLIP-seq
MIRT2013338	hsa-miR-3682-5p	CLIP-seq
MIRT2013339	hsa-miR-3920	CLIP-seq
MIRT2013340	hsa-miR-4427	CLIP-seq
MIRT2013341	hsa-miR-4659a-3p	CLIP-seq
MIRT2013342	hsa-miR-4659b-3p	CLIP-seq
MIRT2013343	hsa-miR-4680-3p	CLIP-seq
MIRT2013344	hsa-miR-4700-3p	CLIP-seq
MIRT2013345	hsa-miR-4712-5p	CLIP-seq
MIRT2013346	hsa-miR-4762-3p	CLIP-seq
MIRT2013347	hsa-miR-4778-3p	CLIP-seq
MIRT2013348	hsa-miR-5095	CLIP-seq
MIRT2013349	hsa-miR-770-5p	CLIP-seq
MIRT2013337	hsa-miR-1278	CLIP-seq
MIRT2245559	hsa-miR-2053	CLIP-seq
MIRT2245560	hsa-miR-3160-3p	CLIP-seq
MIRT2013339	hsa-miR-3920	CLIP-seq
MIRT2245561	hsa-miR-4433	CLIP-seq
MIRT2245562	hsa-miR-4459	CLIP-seq
MIRT2245563	hsa-miR-4476	CLIP-seq
MIRT2245564	hsa-miR-4487	CLIP-seq
MIRT2245565	hsa-miR-4676-5p	CLIP-seq
MIRT2245566	hsa-miR-4691-5p	CLIP-seq
MIRT2013344	hsa-miR-4700-3p	CLIP-seq
MIRT2013345	hsa-miR-4712-5p	CLIP-seq
MIRT2013346	hsa-miR-4762-3p	CLIP-seq
MIRT2245567	hsa-miR-4768-3p	CLIP-seq
MIRT2245568	hsa-miR-4779	CLIP-seq
MIRT2013348	hsa-miR-5095	CLIP-seq
MIRT2245569	hsa-miR-558	CLIP-seq
MIRT2245570	hsa-miR-569	CLIP-seq
MIRT2245571	hsa-miR-575	CLIP-seq
MIRT2013349	hsa-miR-770-5p	CLIP-seq
MIRT2548817	hsa-miR-3119	CLIP-seq
MIRT2548818	hsa-miR-3124-3p	CLIP-seq
MIRT2548819	hsa-miR-3160-5p	CLIP-seq
MIRT2548820	hsa-miR-3163	CLIP-seq
MIRT2548821	hsa-miR-337-3p	CLIP-seq
MIRT2548822	hsa-miR-340	CLIP-seq
MIRT2548823	hsa-miR-3685	CLIP-seq
MIRT2548824	hsa-miR-384	CLIP-seq
MIRT2245566	hsa-miR-4691-5p	CLIP-seq
MIRT2548825	hsa-miR-4699-3p	CLIP-seq
MIRT2548826	hsa-miR-4797-5p	CLIP-seq
MIRT2548817	hsa-miR-3119	CLIP-seq
MIRT2548818	hsa-miR-3124-3p	CLIP-seq
MIRT2548819	hsa-miR-3160-5p	CLIP-seq
MIRT2548821	hsa-miR-337-3p	CLIP-seq
MIRT2548823	hsa-miR-3685	CLIP-seq
MIRT2548824	hsa-miR-384	CLIP-seq
MIRT2245566	hsa-miR-4691-5p	CLIP-seq
MIRT2548825	hsa-miR-4699-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000049	Function	TRNA binding	IEA
GO:0002161	Function	Aminoacyl-tRNA editing activity	IEA
GO:0004822	Function	Isoleucine-tRNA ligase activity	IBA	21873635
GO:0004822	Function	Isoleucine-tRNA ligase activity	TAS
GO:0005524	Function	ATP binding	IEA
GO:0005739	Component	Mitochondrion	IBA	21873635
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006418	Process	TRNA aminoacylation for protein translation	TAS
GO:0006428	Process	Isoleucyl-tRNA aminoacylation	IBA	21873635
GO:0032543	Process	Mitochondrial translation	IBA	21873635
GO:0106074	Process	Aminoacyl-tRNA metabolism involved in translational fidelity	IEA

Other IDs

• MIM: 612801
• HGNC: 29685
• e!Ensembl: ENSG00000067704

Protein

• UniProt ID: Q9NSE4
• Protein name: Isoleucine--tRNA ligase, mitochondrial (EC 6.1.1.5) (Isoleucyl-tRNA synthetase) (IleRS)
• Protein function: Aminoacyl-tRNA synthetase that catalyzes the specific attachment of isoleucine to its cognate tRNA (tRNA(Ile)).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00133	tRNA-synt_1	87 → 712	tRNA synthetases class I (I, L, M and V)	Family
  PF08264	Anticodon_1	756 → 921	Anticodon-binding domain of tRNA ligase	Domain
  PF06827	zf-FPG_IleRS	984 → 1008	Zinc finger found in FPG and IleRS	Domain

• Sequence:

  MRWGLRPRGPGAAALATARSLWGTPRLPCSPGWQGATKRLLVRSVSGASNHQPNSNSGRY
  RDTVLLPQTSFPMKLLGRQQPDTELEIQQKCGFSELYSWQRERKVKTEFCLHDGPPYANG
  DPHVGHALNKILKDIANRFHMMNGSKIHFVPGWDCHGLPIEIKVLSELGREAQNLSAMEI
  RKKARSFAKAAIEKQKSAFIRWGIMADWNNCYYTFDGKYEAKQLRTFYQMYDKGLVYRSY
  KPVFWSPSSRTALAEAELEYNPEHVSRSIYVKFPLLKPSPKLASLIDGSSPVSILVWTTQ
  PWTIPANEAVCYMPESKYAVVKCSKSGDLYVLAADKVASVASTLETTFETISTLSGVDLE
  NGTCSHPLIPDKASPLLPANHVTMAKGTGLVHTAPAHGMEDYGVASQHNLPMDCLVDEDG
  VFTDVAGPELQNKAVLEEGTDVVIKMLQTAKNLLKEEKLVHSYPYDWRTKKPVVIRASKQ
  WFINITDIKTAAKELLKKVKFIPGSALNGMVEMMDRRPYWCISRQRVWGVPIPVFHHKTK
  DEYLINSQTTEHIVKLVEQHGSDIWWTLPPEQLLPKEVLSEVGGPDALEYVPGQDILDIW
  FDSGTSWSYVLPGPDQRADLYLEGKDQLGGWFQSSLLTSVAARKRAPYKTVIVHGFTLGE
  KGEKMSKSLGNVIHPDVVVNGGQDQSKEPPYGADVLRWWVADSNVFTEVAIGPSVLNAAR
  DDISKLRNTLRFLLGNVADFNPETDSIPVNDMYVIDQYMLHLLQDLANKITELYKQYDFG
  KVVRLLRTFYTRELSNFYFSIIKDRLYCEKENDPKRRSCQTALVEILDVIVRSFAPILPH
  LAEEVFQHIPYIKEPKSVFRTGWISTSSIWKKPGLEEAVESACAMRDSFLGSIPGKNAAE
  YKVITVIEPGLLFEIIEMLQSEETSSTSQLNELMMASESTLLAQEPREMTADVIELKGKF
  LINLEGGDIREESSYKVIVMPTTKEKCPRCWKYTAESSDTLCPRCAEVVSGK

• Sequence length: 1012

Pathways

KEGG:

Aminoacyl-tRNA biosynthesis

Reactome:

Mitochondrial tRNA aminoacylation

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Brachydactyly	Brachydactyly	rs121908949, rs28937580, rs121909082, rs104894122, rs863223289, rs863223290, rs104894121, rs1587657302, rs863223292, rs74315386, rs74315387, rs28936397, rs753691079, rs121909348, rs121917852, rs121917853, rs121917854, rs121917855, rs121917859, rs121917861, rs267606873, rs267606872, rs267606985, rs267606986, rs267606987, rs267606988, rs28933082, rs397514519, rs869025613, rs869025614, rs886039878, rs1553540620, rs1057518333, rs1948841937, rs1948868228, rs1948842030, rs1948842142
Cataract	Cataract	rs118203965, rs118203966, rs104893685, rs121908938, rs104894175, rs121909048, rs28937573, rs121909049, rs121909050, rs74315488, rs80358200, rs80358203, rs121434643, rs56141211, rs132630322, rs121917775, rs121917735, rs121917736, rs137853199, rs137853200, rs121917867, rs121917869, rs121913555, rs104893736, rs121909595, rs121909596, rs121909597, rs28931605, rs121909598, rs104893618, rs1695062782, rs74315486, rs74315487, rs74315490, rs74315489, rs745938679, rs1566402656, rs74315439, rs74315441, rs121912973, rs121917823, rs1593332981, rs121917825, rs121917827, rs113994108, rs387906963, rs387906964, rs1240503246, rs387906965, rs387906966, rs750207077, rs387907336, rs387907337, rs387907342, rs140332366, rs397514703, rs398122937, rs398122378, rs398122392, rs398122944, rs137853924, rs398122947, rs397515623, rs397515624, rs397515625, rs397515626, rs398122948, rs587778872, rs398123066, rs587777601, rs370424081, rs786205221, rs786205222, rs864309684, rs864309688, rs864309701, rs864309689, rs864309690, rs864309681, rs864309686, rs864309696, rs864309693, rs864309687, rs864309691, rs864309692, rs864309695, rs864309678, rs864309685, rs864309700, rs864309698, rs864309683, rs864309682, rs864309679, rs111534978, rs864309680, rs864309702, rs864622780, rs756898971, rs869312732, rs775038545, rs878852983, rs1114167312, rs1114167313, rs1114167314, rs1114167315, rs1114167307, rs886041410, rs886041412, rs1057518738, rs1057517926, rs1057518878, rs1057519616, rs12799308, rs1064793935, rs1064797219, rs1085307126, rs1085307127, rs765628635, rs1114167427, rs1114167433, rs1554744860, rs1554743428, rs747093432, rs1411557416, rs1555179713, rs1481963503, rs1555549755, rs1456161420, rs1555547008, rs1555889308, rs1555888762, rs766522434, rs1264025914, rs1553585262, rs1567671947, rs1337897299, rs764945940, rs1307969607, rs949335475, rs1184095219, rs776129797, rs1569203234, rs1567668570, rs749141857, rs764098604, rs1184398243, rs1578956689, rs1568480054, rs1564745688, rs1564722302, rs1564723150, rs1571175950, rs1569602837, rs1576552712, rs1575369255, rs981126461, rs1570403798, rs200557771, rs1477743112, rs1651879427, rs1651881222, rs1651919374, rs2024441691, rs148284531, rs1246080692	25130867
Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia	CATARACTS, GROWTH HORMONE DEFICIENCY, SENSORY NEUROPATHY, SENSORINEURAL HEARING LOSS, AND SKELETAL DYSPLASIA, Cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome	rs151241066, rs1571845061, rs146618526, rs1571865562, rs1571863769	28328135, 25130867, 30041933, 27078007, 30419932
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
Hearing loss	Sensorineural Hearing Loss (disorder)	rs267607135, rs267606855, rs779841884, rs267606854, rs28942097, rs121908073, rs121908076, rs74315289, rs121908144, rs111033313, rs74315437, rs121908348, rs121908349, rs121908350, rs397515359, rs180177151, rs180177154, rs180177153, rs35689081, rs35887622, rs80338944, rs104894396, rs104894398, rs80338947, rs80338948, rs80338942, rs104894402, rs104894403, rs80338945, rs28931594, rs80338940, rs80338941, rs80356590, rs80338950, rs387906706, rs387906707, rs387906708, rs398122848, rs387907016, rs587776894, rs387907088, rs397515411, rs370965183, rs398122930, rs199897298, rs111033187, rs111033448, rs199606180, rs111033284, rs397516413, rs111033305, rs111033220, rs111033256, rs111033297, rs111033253, rs104894408, rs111033295, rs397516874, rs76434661, rs111033335, rs397517323, rs111033247, rs367928692, rs374793617, rs143939430, rs397515605, rs80338939, rs200656442, rs779748859, rs587781261, rs587781262, rs143343083, rs200147906, rs730880338, rs797044491, rs146281367, rs756484720, rs869025593, rs201306709, rs540895576, rs777777359, rs879255246, rs1554358720, rs142498437, rs377145777, rs1057517519, rs779077039, rs952741388, rs1060499797, rs764139009, rs1060499590, rs1064794012, rs1064797115, rs756790858, rs775633137, rs1554952443, rs1554952193, rs782063761, rs1199012623, rs756147087, rs1555648043, rs1555661490, rs1553196233, rs781546107, rs111033190, rs775428246, rs782539587, rs537227442, rs148695069, rs1554835827, rs953422571, rs1554834186, rs1554834161, rs1554835103, rs1554577339, rs1554577402, rs768471577, rs782279338, rs781951909, rs998045226, rs375759781, rs755804651, rs1557458426, rs767797828, rs538027448, rs1559366084, rs367688416, rs1558480402, rs1558490542, rs1559870857, rs1560690591, rs1561299289, rs1562817224, rs1562817529, rs1562822565, rs1562835391, rs1564113368, rs1564554255, rs773851192, rs1564555240, rs761261855, rs1564805114, rs1565522273, rs1565127413, rs781790246, rs1565430886, rs1565469959, rs746667217, rs1565819402, rs1565855932, rs150529554, rs1567939793, rs201866631, rs754472294, rs1559372512, rs1558464965, rs1558488902, rs775062249, rs1226171550, rs1561590396, rs765574676, rs762876554, rs757327146, rs1564949059, rs1565519673, rs368050948, rs1565541888, rs781989117, rs1565402473, rs750358148, rs1386887007, rs1209665716, rs1567641234, rs1237955948, rs1569042782, rs752672077, rs146689036, rs1560070780, rs149712664, rs1564556995, rs762226905, rs773573968, rs1568528171, rs1198256157, rs377267777, rs370564476, rs1577876794, rs747787770, rs759432278, rs1043716893, rs1581138934, rs2033773650, rs1421964916, rs771766431, rs780917129, rs1895773215, rs1895769400, rs761543680, rs1565920060
Isolated somatotropin deficiency	Isolated somatotropin deficiency	rs797044450, rs71640277, rs863223306, rs2144738731, rs863223307, rs2144739370, rs863223309, rs863223310, rs137853223, rs2144739380, rs2144739391
Leigh syndrome	Leigh Disease, LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY, Leigh Syndrome Due To Mitochondrial Complex II Deficiency, Leigh Syndrome due to Mitochondrial Complex III Deficiency, Leigh Syndrome due to Mitochondrial Complex IV Deficiency, Leigh Syndrome due to Mitochondrial Complex V Deficiency	rs267606829, rs137852863, rs121908577, rs1445075330, rs121908985, rs104893898, rs28939679, rs104894705, rs1568985256, rs199476144, rs199474672, rs118192098, rs118192100, rs199476133, rs199476135, rs199476138, rs267606614, rs207459999, rs199476104, rs199476105, rs199476107, rs199476109, rs267606893, rs267606897, rs28384199, rs267606890, rs199476117, rs267606891, rs267606889, rs199476118, rs199476123, rs121918657, rs28933402, rs782316919, rs121913659, rs768050261, rs121913660, rs121913661, rs201431517, rs1556423632, rs587776949, rs201889294, rs398123061, rs398124308, rs587776434, rs587776438, rs587776440, rs1556423547, rs587776497, rs587776498, rs797045055, rs375169579, rs782490558, rs782190413, rs863224228, rs863224229, rs757486575, rs750831299, rs863224926, rs864309500, rs761389904, rs147816470, rs150613320, rs782623477, rs782007828, rs782349178, rs1057517942, rs199683937, rs1057521059, rs1057520688, rs781948238, rs782024654, rs782289759, rs1131692037, rs1161932777, rs1242159511, rs773850151, rs1553997617, rs1554768246, rs1410388157, rs1554059248, rs1554062427, rs1267554976, rs1391748504, rs376281345, rs772294726, rs1554768333, rs149718203, rs536758576, rs1555066709, rs1053850536, rs1564349176, rs782061187, rs762620949, rs1219762677, rs761097220, rs747359752, rs782609482, rs1229474296, rs782682492, rs1564349087, rs1588688823, rs1588691786, rs1603222000, rs1603223363, rs1603224017, rs1603220522, rs1603221804, rs1603222011, rs1603222119, rs1574663066, rs778120270, rs1574675683, rs1559047521, rs747249702, rs1244071473, rs1588693841, rs746519257, rs1591111808, rs766830864, rs1363125797, rs1836430953	25130867, 30041933, 25613900, 29980628, 30041933, 25130867, 25613900, 29980628, 30041933, 29980628, 25130867, 25613900, 25130867, 29980628, 25613900, 30041933
Nystagmus	Nystagmus	rs137852207, rs137852208, rs1928435502, rs137852209, rs137852210, rs1929191668, rs137852211, rs137852212, rs2124209414, rs387906720, rs387906721, rs1602791884, rs786205896
Peripheral neuropathy	Peripheral Neuropathy	rs28940294, rs137852972, rs104894715, rs121918312, rs137852667, rs2101018240, rs149782619, rs397514490, rs62636502, rs797044802, rs879253752, rs879253869, rs777219451, rs538412810, rs759785462, rs1241595912, rs1553259707, rs757937208, rs144183238, rs1586128169, rs765346218	25130867
Scoliosis	Scoliosis, unspecified	rs1057518828, rs147296805, rs758163506, rs1555613564, rs1596852902, rs1596853067, rs1596853085
Adrenal insufficiency	Secondary Adrenal Insufficiency	rs104894118, rs104894119
Spondyloepimetaphyseal dysplasia	Spondyloepimetaphyseal disorder	rs121909497, rs121909499, rs879255602, rs878853267, rs779218846, rs878852980, rs878852981, rs1325869434, rs1565256477, rs1597675888, rs1597675890, rs1597676540, rs369033671
Spondyloepiphyseal dysplasia	Spondyloepiphyseal Dysplasia	rs72555367, rs121908950, rs121908951, rs121908952, rs104893637, rs104893639, rs387906534, rs121913568, rs606231241, rs606231242, rs786200933, rs606231243, rs786200934, rs397515546, rs797045099, rs869312907, rs886041895, rs760093841, rs374379931, rs1471554906, rs1567185220, rs1567186585, rs1592198747, rs1239366051, rs1592197682

Unknown
Disease name	Disease term	dbSNP ID	References
Achalasia	Esophageal Achalasia
Cerebral cortical atrophy	Cerebral cortical atrophy
Developmental dysplasia of the hip	Congenital Dysplasia Of The Hip
Corpus luteum cyst	Corpus Luteum Cyst		21239663
Dwarfism	Dwarfism
Esotropia	Esotropia
Horizontal nystagmus	Horizontal Nystagmus
Keratoconjunctivitis sicca	Keratoconjunctivitis Sicca
Malocclusion	Class III malocclusion
Microstomia	Microstomia
Motor delay	Clumsiness - motor delay
Necrotizing encephalomyelopathy	Necrotizing encephalopathy, infantile subacute, of Leigh		25130867, 25613900, 29980628, 30041933
Nervous system diseases	Peripheral Nervous System Diseases
Osteopenia	Osteopenia
Ovarian cysts	Ovarian Cysts		21239663
Ptosis	Blepharoptosis, Ptosis	rs139920573
Sensorimotor neuropathy	Sensorimotor neuropathy
Sensorineural hearing loss	Prelingual sensorineural hearing impairment, Sensorineural hearing loss, bilateral
Sensory neuropathy	Sensory neuropathy
Somatotropin deficiency	Somatotropin deficiency