AARS1 (alanyl-tRNA synthetase 1)

Gene

• Entrez ID: 16
• Gene name: Alanyl-tRNA synthetase 1
• Gene symbol: AARS1
• Synonyms (NCBI Gene): AARS, CMT2N, DEE29, EIEE29, HDLS2, TTD8
• Chromosome: 16
• Chromosome location: 16q22.1
• Summary: The human alanyl-tRNA synthetase (AARS) belongs to a family of tRNA synthases, of the class II enzymes. Class II tRNA synthases evolved early in evolution and are highly conserved. This is reflected by the fact that 498 of the 968-residue polypeptide hu

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs115882953	G>A,C,T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, intron variant, coding sequence variant, missense variant
rs138081804	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Non coding transcript variant, coding sequence variant, missense variant
rs143370729	T>C	Uncertain-significance, pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs147319762	T>C	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, non coding transcript variant, missense variant
rs150080663	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, non coding transcript variant, synonymous variant
rs199976742	T>C	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Non coding transcript variant, missense variant, coding sequence variant
rs267606621	C>T	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs387906792	T>A	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs576221121	C>T	Conflicting-interpretations-of-pathogenicity, likely-benign	Missense variant, non coding transcript variant, coding sequence variant
rs750552137	A>G	Conflicting-interpretations-of-pathogenicity, likely-benign	Synonymous variant, non coding transcript variant, coding sequence variant
rs758183257	G>A	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs763937206	AGTAA>-	Likely-pathogenic	Inframe indel, coding sequence variant, stop gained, non coding transcript variant
rs765398055	T>C	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant, non coding transcript variant
rs771059047	C>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, non coding transcript variant, missense variant
rs777601008	G>A	Uncertain-significance, pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs786205157	T>G	Pathogenic, likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs797044801	T>G	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, non coding transcript variant, missense variant
rs1064795664	G>A	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1480620711	G>A	Likely-pathogenic	Missense variant, intron variant, coding sequence variant
rs1555542415	A>G	Likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs1597434047	->A	Likely-pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000049	Function	TRNA binding	IEA
GO:0000049	Function	TRNA binding	TAS	7654687
GO:0000166	Function	Nucleotide binding	IEA
GO:0002161	Function	Aminoacyl-tRNA deacylase activity	IBA
GO:0002161	Function	Aminoacyl-tRNA deacylase activity	IDA	28493438
GO:0002161	Function	Aminoacyl-tRNA deacylase activity	IEA
GO:0002196	Function	Ser-tRNA(Ala) deacylase activity	IEA
GO:0002196	Function	Ser-tRNA(Ala) deacylase activity	ISS
GO:0003676	Function	Nucleic acid binding	IEA
GO:0003723	Function	RNA binding	IEA
GO:0004812	Function	Aminoacyl-tRNA ligase activity	IEA
GO:0004813	Function	Alanine-tRNA ligase activity	IBA
GO:0004813	Function	Alanine-tRNA ligase activity	IDA	27622773, 28493438
GO:0004813	Function	Alanine-tRNA ligase activity	IEA
GO:0004813	Function	Alanine-tRNA ligase activity	TAS
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IDA	38512451
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IDA	38512451
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	TAS	7654687
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006400	Process	TRNA modification	IEA
GO:0006400	Process	TRNA modification	ISS
GO:0006412	Process	Translation	IEA
GO:0006418	Process	TRNA aminoacylation for protein translation	TAS
GO:0006419	Process	Alanyl-tRNA aminoacylation	IBA
GO:0006419	Process	Alanyl-tRNA aminoacylation	IDA	27622773, 28493438
GO:0006419	Process	Alanyl-tRNA aminoacylation	IEA
GO:0006419	Process	Alanyl-tRNA aminoacylation	IMP	33909043
GO:0006419	Process	Alanyl-tRNA aminoacylation	TAS	7761427
GO:0008033	Process	TRNA processing	TAS	7654687
GO:0008270	Function	Zinc ion binding	IEA
GO:0016020	Component	Membrane	HDA	19946888
GO:0016597	Function	Amino acid binding	IEA
GO:0016874	Function	Ligase activity	IEA
GO:0021680	Process	Cerebellar Purkinje cell layer development	IEA
GO:0030330	Process	DNA damage response, signal transduction by p53 class mediator	IDA	15149599
GO:0030330	Process	DNA damage response, signal transduction by p53 class mediator	IMP	20160708
GO:0035329	Process	Hippo signaling	IDA	18579750, 19324877, 35429439
GO:0035329	Process	Hippo signaling	TAS	18158288
GO:0035332	Process	Positive regulation of hippo signaling	IDA	38512451
GO:0043039	Process	TRNA aminoacylation	IEA
GO:0043524	Process	Negative regulation of neuron apoptotic process	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0050885	Process	Neuromuscular process controlling balance	IEA
GO:0050905	Process	Neuromuscular process	IEA
GO:0051402	Process	Neuron apoptotic process	IEA
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:0106074	Process	Aminoacyl-tRNA metabolism involved in translational fidelity	IEA
GO:0140018	Process	Regulation of cytoplasmic translational fidelity	IEA
GO:0141207	Function	Peptide lactyltransferase (ATP-dependent) activity	IDA	38512451, 38653238, 39322678
GO:0141207	Function	Peptide lactyltransferase (ATP-dependent) activity	IEA
GO:1901797	Process	Negative regulation of signal transduction by p53 class mediator	IDA	38653238

Other IDs

• MIM: 601065
• HGNC: 20
• e!Ensembl: ENSG00000090861

Protein

• UniProt ID: P49588
• Protein name: Alanine--tRNA ligase, cytoplasmic (EC 6.1.1.7) (Alanyl-tRNA synthetase) (AlaRS) (Protein lactyltransferase AARS1) (EC 6.-.-.-) (Renal carcinoma antigen NY-REN-42)
• Protein function: Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala) (PubMed:27622773, PubMed:27911835, PubMed:28493438, PubMed:33909043)
• PDB: 4XEM, 4XEO, 5KNN, 5T5S, 5T76, 5V59
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01411	tRNA-synt_2c	9 → 597	tRNA synthetases class II (A)	Family
  PF07973	tRNA_SAD	694 → 753	Threonyl and Alanyl tRNA synthetase second additional domain	Domain
  PF02272	DHHA1	812 → 959	DHHA1 domain	Family

• Sequence:

  MDSTLTASEIRQRFIDFFKRNEHTYVHSSATIPLDDPTLLFANAGMNQFKPIFLNTIDPS
  HPMAKLSRAANTQKCIRAGGKHNDLDDVGKDVYHHTFFEMLGSWSFGDYFKELACKMALE
  LLTQEFGIPIERLYVTYFGGDEAAGLEADLECKQIWQNLGLDDTKILPGNMKDNFWEMGD
  TGPCGPCSEIHYDRIGGRDAAHLVNQDDPNVLEIWNLVFIQYNREADGILKPLPKKSIDT
  GMGLERLVSVLQNKMSNYDTDLFVPYFEAIQKGTGARPYTGKVGAEDADGIDMAYRVLAD
  HARTITVALADGGRPDNTGRGYVLRRILRRAVRYAHEKLNASRGFFATLVDVVVQSLGDA
  FPELKKDPDMVKDIINEEEVQFLKTLSRGRRILDRKIQSLGDSKTIPGDTAWLLYDTYGF
  PVDLTGLIAEEKGLVVDMDGFEEERKLAQLKSQGKGAGGEDLIMLDIYAIEELRARGLEV
  TDDSPKYNYHLDSSGSYVFENTVATVMALRREKMFVEEVSTGQECGVVLDKTCFYAEQGG
  QIYDEGYLVKVDDSSEDKTEFTVKNAQVRGGYVLHIGTIYGDLKVGDQVWLFIDEPRRRP
  IMSNHTATHILNFALRSVLGEADQKGSLVAPDRLRFDFTAKGAMSTQQIKKAEEIANEMI
  EAAKAVYTQDCPLAAAKAIQGLRAVFDETYPDPVRVVSIGVPVSELLDDPSGPAGSLTSV
  EFCGGTHLRNSSHAGAFVIVTEEAIAKGIRRIVAVTGAEAQKALRKAESLKKCLSVMEAK
  VKAQTAPNKDVQREIADLGEALATAVIPQWQKDELRETLKSLKKVMDDLDRASKADVQKR
  VLEKTKQFIDSNPNQPLVILEMESGASAKALNEALKLFKMHSPQTSAMLFTVDNEAGKIT
  CLCQVPQNAANRGLKASEWVQQVSGLMDGKGGGKDVSAQATGKNVGCLQEALQLATSFAQ
  LRLGDVKN

• Sequence length: 968

Pathways

KEGG:

Aminoacyl-tRNA biosynthesis

Reactome:

Cytosolic tRNA aminoacylation

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
AARS1-related disorder	Likely pathogenic; Pathogenic	rs267606621	RCV004730838
Charcot-Marie-Tooth disease	Likely pathogenic; Pathogenic	rs267606621, rs1597446183	RCV000192253 RCV001027508
Charcot-Marie-Tooth disease axonal type 2N	Pathogenic; Likely pathogenic	rs2152160733, rs1398433261, rs2152160758, rs786205157, rs145859060, rs267606621, rs1456469605, rs2507028484, rs1555542415	RCV001806263 RCV002247706 RCV002249209 RCV003311703 RCV005363055 RCV000008987 RCV003231055 RCV003336696 RCV000664214
Charcot-Marie-Tooth disease type 2	Pathogenic; Likely pathogenic	rs1960409206, rs1211684571, rs2152160733, rs1173826571, rs766251338, rs1960065852, rs752548366, rs768830699, rs369135192, rs2152160643, rs977976041, rs2152166762, rs1398433261, rs761931081, rs2507013974, rs747434741, rs1960557616, rs2506989427, rs1567601355, rs1292379905, rs145859060, rs267606621, rs2507003569, rs1361458223, rs754266971, rs772774828, rs2506997974, rs2507012689, rs1960369184, rs781347519, rs1064795664, rs763937206, rs1555540896, rs866662905, rs1567604571, rs1597435337, rs1597435790, rs1597446183, rs1597448762, rs758183257, rs1960348987, rs756337758, rs1438690757, rs868097991	RCV001340895 RCV002241581 RCV002541169 RCV002236815 RCV002239803 RCV002236861 RCV002236873 RCV002236876 RCV002236910 RCV002236920 RCV002236943 RCV002236964 RCV002239845 RCV002236980 RCV002583497 RCV002631875 RCV002672203 RCV002791374 RCV002863664 RCV002895720 RCV003777670 RCV000168406 RCV003582189 RCV003582466 RCV003582875 RCV003582968 RCV003744229 RCV003743097 RCV003743253 RCV003845486 RCV000468199 RCV002230949 RCV003767415 RCV000653936 RCV000697803 RCV000700148 RCV000803092 RCV000792801 RCV000807351 RCV000807609 RCV002236061 RCV001068179 RCV001216699 RCV001206722 RCV002537705
Colon adenocarcinoma	Likely pathogenic; Pathogenic	rs766251338	RCV005930003
Developmental and epileptic encephalopathy, 29	Pathogenic; Likely pathogenic	rs2152166979, rs2152156655, rs2152153611, rs2152154412, rs786205157, rs2506997702, rs1555539157, rs758183257	RCV001509582 RCV001509585 RCV001806265 RCV001804208 RCV000170341 RCV003479740 RCV000664218 RCV000995471
Hereditary diffuse leukoencephalopathy with spheroids	Likely pathogenic; Pathogenic	rs2152166694	RCV001728170
Leukoencephalopathy, hereditary diffuse, with spheroids 2	Likely pathogenic; Pathogenic	rs2152166694, rs2507016563	RCV001806251 RCV002281620
Trichothiodystrophy 8, nonphotosensitive	Pathogenic; Likely pathogenic	rs2152149706, rs2507018118	RCV001804212 RCV003990408

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
AARS-related disorder	Conflicting classifications of pathogenicity	rs143370729	RCV003335174
Acute myeloid leukemia	Benign	rs7192000	RCV005904203
Cervical cancer	Benign	rs7192000	RCV005904204
Charcot-Marie-Tooth disease, type I	Uncertain significance	rs1597435167, rs1422332765	RCV000857008 RCV000857013
Clear cell carcinoma of kidney	Conflicting classifications of pathogenicity; Uncertain significance	rs755350912, rs200586605, rs138490305	RCV005930004 RCV005889819 RCV005898452
Distal spinal muscular atrophy	Uncertain significance	rs1597443484	RCV000857014
Familial cancer of breast	Likely benign; Uncertain significance	rs762546700, rs200557581	RCV005900383 RCV005901709
Gastric cancer	Conflicting classifications of pathogenicity; Benign	rs200586605, rs7192000	RCV005889820 RCV005904206
Hepatocellular carcinoma	Likely benign	rs775476419	RCV005913775
Lung cancer	Benign	rs7192000	RCV005904208
Malignant tumor of esophagus	Conflicting classifications of pathogenicity; Likely benign	rs145581652, rs555241883	RCV005894527 RCV005898912
Malignant tumor of urinary bladder	Uncertain significance	rs369135192, rs200578293	RCV005890968 RCV005901667
Ovarian serous cystadenocarcinoma	Conflicting classifications of pathogenicity; Benign; Likely benign	rs200586605, rs200965527, rs145581652, rs115882953, rs7192000	RCV005889821 RCV005893567 RCV005894529 RCV005899634 RCV005904207
Peripheral neuropathy	Conflicting classifications of pathogenicity	rs777601008	RCV001731192
Sarcoma	Conflicting classifications of pathogenicity; Benign	rs145581652, rs7192000	RCV005894528 RCV005904205
See cases	Uncertain significance	rs1337985053, rs1960352267	RCV001199243 RCV001199310
Squamous cell carcinoma of the head and neck	Uncertain significance	rs1567610606	RCV005939487
Thymoma	Conflicting classifications of pathogenicity	rs747431164	RCV005894530
Uterine corpus endometrial carcinoma	Conflicting classifications of pathogenicity	rs115882953	RCV005899635

Associations from Text Mining
Disease Name	Relationship Type	References
Alcoholic Neuropathy	Associate	20045102, 25817015, 26032230
Antisynthetase syndrome	Associate	11686873
Brain Diseases	Associate	25817015, 28493438
Carcinogenesis	Associate	36991000
Charcot Marie Tooth Disease	Associate	22009580, 22573628, 26032230, 28493438, 35971119
Charcot Marie Tooth Disease Axonal Type 2n	Associate	22009580, 25817015, 33753480, 39456965
Charcot Marie Tooth disease Type 2B	Associate	39456965
Demyelinating Diseases	Associate	25817015, 28493438
Dermatomyositis	Associate	11686873
Distal Hereditary Motor Neuropathy Type II	Associate	22573628, 26032230
Duodenal Neoplasms	Associate	36991000
Ectrodactyly	Associate	26032230
Epilepsy	Associate	28493438
Genetic Diseases Inborn	Associate	28493438
Hereditary Diffuse Leukoencephalopathy with Spheroids	Associate	31775912
Immunologic Deficiency Syndromes	Associate	37742077
Inflammation	Associate	35971119
Inherited Peripheral Neuropathy	Associate	30373780
Leukemic Infiltration	Associate	22573628
Leukodystrophy Metachromatic	Associate	24808023, 31280959
Leukoencephalopathies	Associate	25817015, 31775912, 34446925
Lung Diseases Interstitial	Associate	11686873, 17393393
Microcephaly	Associate	28493438
Mitochondrial Diseases	Associate	26811336
Monoclonal Gammopathy of Undetermined Significance	Associate	37587064
Multiple Myeloma	Associate	37587064
Muscle Spasticity	Associate	28493438
Myotonic Dystrophy	Associate	22886382
Neoplasms	Associate	25476837, 36991000, 37587064
Nerve Degeneration	Associate	20045102
Nervous System Autoimmune Disease Experimental	Associate	22549773
Nervous System Diseases	Associate	35971119, 37010095
Neurodegenerative Diseases	Associate	20045102
Neurologic Manifestations	Associate	28493438
Neuronopathy Distal Hereditary Motor Type V	Associate	26032230
Peripheral Nervous System Diseases	Associate	25817015
Polymyositis	Associate	11686873
Upper Extremity Deformities Congenital	Associate	26032230