AARS1

Summary

AARS1 (alanyl-tRNA synthetase 1, HGNC:20) is a protein-coding gene on chromosome 16q22.1, encoding Alanine–tRNA ligase, cytoplasmic (P49588). 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). It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

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 human AARS shares 41% identity witht the E.coli protein. tRNA synthases are the enzymes that interpret the RNA code and attach specific aminoacids to the tRNAs that contain the cognate trinucleotide anticodons. They consist of a catalytic domain which interacts with the amino acid acceptor-T psi C helix of the tRNA, and a second domain which interacts with the rest of the tRNA structure.

Source: NCBI Gene 16 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 29 (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 1,730 total — 70 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 189
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001605

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20
Approved symbol	AARS1
Name	alanyl-tRNA synthetase 1
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	CMT2N, AlaRS
Ensembl gene	ENSG00000090861
Ensembl biotype	protein_coding
OMIM	601065
Entrez	16

Gene structure

Transcript identifiers

Ensembl transcripts: 62 — 31 protein_coding, 16 nonsense_mediated_decay, 13 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000261772, ENST00000564359, ENST00000565361, ENST00000566969, ENST00000567490, ENST00000569790, ENST00000569825, ENST00000674512, ENST00000674652, ENST00000674691, ENST00000674768, ENST00000674811, ENST00000674848, ENST00000674962, ENST00000674963, ENST00000675035, ENST00000675045, ENST00000675120, ENST00000675133, ENST00000675155, ENST00000675270, ENST00000675297, ENST00000675338, ENST00000675371, ENST00000675403, ENST00000675569, ENST00000675588, ENST00000675643, ENST00000675691, ENST00000675751, ENST00000675853, ENST00000675917, ENST00000675953, ENST00000675986, ENST00000676004, ENST00000676040, ENST00000676065, ENST00000676168, ENST00000676209, ENST00000676211, ENST00000676212, ENST00000676247, ENST00000896284, ENST00000896285, ENST00000896286, ENST00000896287, ENST00000896288, ENST00000896289, ENST00000896290, ENST00000896291, ENST00000896292, ENST00000934581, ENST00000934582, ENST00000934583, ENST00000934584, ENST00000934585, ENST00000951922, ENST00000951923, ENST00000951924, ENST00000951925, ENST00000951926, ENST00000951927

RefSeq mRNA: 1 — MANE Select: NM_001605 NM_001605

CCDS: CCDS32474

Canonical transcript exons

ENST00000261772 — 21 exons

Exon	Start	End
ENSE00000579017	70270196	70270340
ENSE00000579020	70267659	70267809
ENSE00000694594	70258033	70258217
ENSE00000694616	70264958	70265102
ENSE00000694625	70268271	70268379
ENSE00000694628	70269618	70269763
ENSE00000694634	70271781	70271972
ENSE00000694646	70276486	70276631
ENSE00000844519	70262346	70262524
ENSE00000844528	70276966	70277154
ENSE00001111982	70282620	70282784
ENSE00001261263	70252298	70252906
ENSE00001316640	70289421	70289506
ENSE00001505580	70253268	70253381
ENSE00001505581	70253714	70253800
ENSE00003552111	70255728	70255836
ENSE00003559520	70261044	70261157
ENSE00003581725	70254621	70254734
ENSE00003583910	70258980	70259186
ENSE00003650916	70265538	70265662
ENSE00003679366	70253919	70254038

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 98.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 75.9456 / max 424.4070, expressed in 1815 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157928	51.8772	1806
157929	23.7673	1807
157927	0.3010	98

Top tissues by expression

302 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	98.32	gold quality
type B pancreatic cell	CL:0000169	98.15	gold quality
frontal pole	UBERON:0002795	98.01	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.00	gold quality
islet of Langerhans	UBERON:0000006	97.72	gold quality
right frontal lobe	UBERON:0002810	97.66	gold quality
prefrontal cortex	UBERON:0000451	97.63	gold quality
middle frontal gyrus	UBERON:0002702	97.61	gold quality
paraflocculus	UBERON:0005351	97.51	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.35	gold quality
frontal cortex	UBERON:0001870	97.25	gold quality
stromal cell of endometrium	CL:0002255	97.17	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.02	gold quality
cingulate cortex	UBERON:0003027	96.99	gold quality
neocortex	UBERON:0001950	96.98	gold quality
cerebellar vermis	UBERON:0004720	96.97	gold quality
anterior cingulate cortex	UBERON:0009835	96.97	gold quality
hypothalamus	UBERON:0001898	96.72	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.71	gold quality
cerebellar cortex	UBERON:0002129	96.70	gold quality
cerebellar hemisphere	UBERON:0002245	96.68	gold quality
olfactory bulb	UBERON:0002264	96.68	gold quality
caudate nucleus	UBERON:0001873	96.67	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.66	gold quality
cerebellum	UBERON:0002037	96.63	gold quality
pons	UBERON:0000988	96.62	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.60	gold quality
parotid gland	UBERON:0001831	96.57	gold quality
putamen	UBERON:0001874	96.57	gold quality
cerebral cortex	UBERON:0000956	96.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting AARS1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-140-5P	99.44	67.20	792
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-7843-5P	98.12	65.26	1421
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-5088-5P	97.97	64.28	487
HSA-MIR-4632-5P	97.82	65.38	1470
HSA-MIR-4329	97.68	66.26	1003
HSA-MIR-203B-5P	97.24	68.54	543
HSA-MIR-6718-5P	97.24	68.15	553
HSA-MIR-203A-5P	96.33	65.03	714

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 9)

• A packaging model in which the gp16 Coiled coil Motif is implicated in the regulation of packaging initiation and assembly of a supramolecular DNA packaging machine on the viral concatemer. (PMID:16513134)
• The binding of gp16 to the prohead/pRNA to constitute the complete and active packaging motor was confirmed by cryo-electron microscopy three-dimensional reconstruction of the prohead/pRNA/gp16 complex (PMID:18674782)
• direct observation of the intersubunit coordination and step size of a ring ATPase, the double-stranded-DNA packaging motor in the bacteriophage phi29 (PMID:19129763)
• The full mechanochemical cycle of the motor, in which the ATPase is a pentameric-ring of gene product 16, involves two phases-an ATP-loading dwell followed by a translocation burst of four 2.5-base-pair steps triggered by hydrolysis product release. (PMID:19794496)
• Kinetic analysis of phi29 DNA packaging motor provides evidence for coordinated intersubunit ATPase activity of gp16. (PMID:22795974)
• Authors confirmed the stoichiometry of phi29 motor ATPase to be a hexamer and provide data suggesting that the phi29 motor ATPase is a member of the classical hexameric AAA+ superfamily. (PMID:23706809)
• Authors report a revolution rather than rotation mechanism for the bacteriophage phi29 DNA packaging motor. (PMID:23763768)
• Results report that the sequential action of the ATPase ring in the DNA packaging motor of bacteriophage phi29 is regulated by an arginine finger that extends from one ATPase subunit to the adjacent unit to promote noncovalent dimer formation. (PMID:27457616)
• NMR structure of a vestigial nuclease provides insight into the evolution of functional transitions in viral dsDNA packaging motors. (PMID:33089330)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	aars1	ENSDARG00000069142
mus_musculus	Aars1	ENSMUSG00000031960
rattus_norvegicus	Aars1	ENSRNOG00000018404
drosophila_melanogaster	AlaRS	FBGN0027094
caenorhabditis_elegans	aars-2	WBGENE00000197

Paralogs (2): AARS2 (ENSG00000124608), AARSD1 (ENSG00000266967)

Protein

Protein identifiers

Alanine–tRNA ligase, cytoplasmic — P49588 (reviewed: P49588)

Alternative names: Alanyl-tRNA synthetase, Protein lactyltransferase AARS1, Renal carcinoma antigen NY-REN-42

All UniProt accessions (18): P49588, A0A6Q8PF33, A0A6Q8PF77, A0A6Q8PFK3, A0A6Q8PFY2, A0A6Q8PG28, A0A6Q8PG62, A0A6Q8PGB5, A0A6Q8PGE8, A0A6Q8PGI8, A0A6Q8PGN5, A0A6Q8PGR9, A0A6Q8PH44, A0A6Q8PHJ2, A0A6Q8PHN5, A0A6Q8PHP3, A0A6Q8PHP7, H3BPK7

UniProt curated annotations — full annotation on UniProt →

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). Also edits incorrectly charged tRNA(Ala) via its editing domain. In presence of high levels of lactate, also acts as a protein lactyltransferase that mediates lactylation of lysine residues in target proteins, such as TEAD1, TP53/p53 and YAP1. Protein lactylation takes place in a two-step reaction: lactate is first activated by ATP to form lactate-AMP and then transferred to lysine residues of target proteins. Acts as an inhibitor of TP53/p53 activity by catalyzing lactylation of TP53/p53. Acts as a positive regulator of the Hippo pathway by mediating lactylation of TEAD1 and YAP1.

Subunit / interactions. Monomer. Interacts with ANKRD16; the interaction is direct.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. ISGylated. Methylation at ‘Lys-943’ by METTL21C.

Disease relevance. Charcot-Marie-Tooth disease, axonal, type 2N (CMT2N) [MIM:613287] An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. The disease is caused by variants affecting the gene represented in this entry. Developmental and epileptic encephalopathy 29 (DEE29) [MIM:616339] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE29 patients manifest severe infantile epileptic encephalopathy, clubfoot, absent deep tendon reflexes, extrapyramidal symptoms, and persistently deficient myelination. The disease is caused by variants affecting the gene represented in this entry. Leukoencephalopathy, hereditary diffuse, with spheroids 2 (HDLS2) [MIM:619661] An autosomal dominant neurodegenerative disorder characterized by progressive cognitive and executive dysfunction, psychiatric disturbances, and neurologic symptoms, such as gait abnormalities, paresis, seizures, and rigidity. Symptom onset is usually in adulthood, although earlier onset has been reported. Some patients have an acute encephalopathic course with severe neurologic decline resulting in early death, whereas other patients have a more protracted and chronic disease course. Neuropathologic examination shows a leukoencephalopathy with axonal spheroids and myelination defects. The disease may be caused by variants affecting the gene represented in this entry. Trichothiodystrophy 8, non-photosensitive (TTD8) [MIM:619691] A form of trichothiodystrophy, a disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder. TTD8 is an autosomal recessive, non-photosensitive form characterized by brittle hair and nails, scaly skin, accompanied by failure to thrive, microcephaly, and neuromotor developmental delay. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. The protein lactyltransferase activity is inhibited by beta-alanine.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. Consists of three domains; the N-terminal catalytic domain, the editing domain and the C-terminal C-Ala domain. The editing domain removes incorrectly charged amino acids, while the C-Ala domain, along with tRNA(Ala), serves as a bridge to cooperatively bring together the editing and aminoacylation centers thus stimulating deacylation of misacylated tRNAs. The C-terminal C-Ala domain (residues 756 to 968) is not required for catalytic activity and can bind DNA (in vitro). The C-terminal C-Ala domain (residues 756 to 968), along with tRNA(Ala), serves as a bridge to cooperatively bring together the editing and aminoacylation centers thus stimulating deacylation of misacylated tRNAs. The human domain can be used in vitro to replace the corresponding domain in E.coli.

Similarity. Belongs to the class-II aminoacyl-tRNA synthetase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P49588-1	1	yes
P49588-2	2

RefSeq proteins (1): NP_001596* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002318	Ala-tRNA-lgiase_IIc	Family
IPR003156	DHHA1_dom	Domain
IPR009000	Transl_B-barrel_sf	Homologous_superfamily
IPR012947	tRNA_SAD	Domain
IPR018162	Ala-tRNA-ligase_IIc_anticod-bd	Homologous_superfamily
IPR018163	Thr/Ala-tRNA-synth_IIc_edit	Homologous_superfamily
IPR018164	Ala-tRNA-synth_IIc_N	Domain
IPR018165	Ala-tRNA-synth_IIc_core	Domain
IPR023033	Ala_tRNA_ligase_euk/bac	Family
IPR045864	aa-tRNA-synth_II/BPL/LPL	Homologous_superfamily
IPR050058	Ala-tRNA_ligase	Family

Pfam: PF01411, PF02272, PF07973

Catalyzed reactions (Rhea), 3 shown:

• tRNA(Ala) + L-alanine + ATP = L-alanyl-tRNA(Ala) + AMP + diphosphate (RHEA:12540)
• (S)-lactate + ATP + H(+) = (S)-lactoyl-AMP + diphosphate (RHEA:80271)
• (S)-lactoyl-AMP + L-lysyl-[protein] = N(6)-[(S)-lactoyl]-L-lysyl-[protein] + AMP + 2 H(+) (RHEA:80275)

UniProt features (115 total): helix 34, sequence variant 16, strand 15, mutagenesis site 14, binding site 11, modified residue 10, turn 7, sequence conflict 4, splice variant 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
4XEM	X-RAY DIFFRACTION	1.28
4XEO	X-RAY DIFFRACTION	1.38
5T76	X-RAY DIFFRACTION	2
5V59	X-RAY DIFFRACTION	2.03
5T5S	X-RAY DIFFRACTION	2.2
5KNN	X-RAY DIFFRACTION	2.68

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49588-F1	90.66	0.70

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (11): 609; 723; 727; 77; 95; 176; 214–216; 216; 239; 243; 605

Post-translational modifications (10): 1, 3, 8, 19, 399, 555, 876, 943, 943, 943

Mutagenesis-validated functional residues (14):

Position	Phenotype
46	in mutant 5a; abolished binding to lactate and protein lactylation; when associated with a-77, a-216 and 239-a–a-241.
77	in mutant 5a; abolished binding to lactate and protein lactylation; when associated with a-46, a-216 and 239-a–a-241. i
100	in mutant 5m; abolished binding to lactate and protein lactylation; when associated with a-77, e-176, d-218 and a-239.
176	in atp-binding mutant; abolished ability to mediate protein lactylation; when associated with a-77 and a-243.
176	in mutant 5m; abolished binding to lactate and protein lactylation; when associated with a-77, a-100, d-218 and a-239.
216	in mutant 5a; abolished binding to lactate and protein lactylation; when associated with a-46, a-77 and 239-a–a-241.
218	in mutant 5m; abolished binding to lactate and protein lactylation; when associated with a-77, a-100, e-176 and a-239.
239–241	in mutant 5a; abolished binding to lactate and protein lactylation; when associated with a-46, a-77 and a-216.
239	in mutant 5m; abolished binding to lactate and protein lactylation; when associated with a-77, a-100, e-176 and d-218.
243	in atp-binding mutant; abolished ability to mediate protein lactylation; when associated with a-77 and a-176.
448	decreases misincorporation of cys instead of ala.
723	decreases editing activity.
750–763	abolished nuclear translocation in presence of lactate.
943	abrogates mettl21c methylation of aars1.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-379716	Cytosolic tRNA aminoacylation
R-HSA-379724	tRNA Aminoacylation
R-HSA-392499	Metabolism of proteins
R-HSA-72766	Translation

MSigDB gene sets: 643 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_CYTOPLASMIC_TRANSLATION, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_AMINO_ACID_ACTIVATION, chr16q22, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_TRNA_METABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, HSIAO_HOUSEKEEPING_GENES, GOBP_REGULATION_OF_TRANSLATIONAL_ELONGATION

GO Biological Process (17): tRNA modification (GO:0006400), tRNA aminoacylation for protein translation (GO:0006418), alanyl-tRNA aminoacylation (GO:0006419), tRNA processing (GO:0008033), cerebellar Purkinje cell layer development (GO:0021680), positive regulation of hippo signaling (GO:0035332), negative regulation of neuron apoptotic process (GO:0043524), neuromuscular process controlling balance (GO:0050885), neuron apoptotic process (GO:0051402), regulation of cytoplasmic translational fidelity (GO:0140018), negative regulation of signal transduction by p53 class mediator (GO:1901797), translation (GO:0006412), DNA damage response, signal transduction by p53 class mediator (GO:0030330), hippo signaling (GO:0035329), tRNA aminoacylation (GO:0043039), neuromuscular process (GO:0050905), aminoacyl-tRNA metabolism involved in translational fidelity (GO:0106074)

GO Molecular Function (14): tRNA binding (GO:0000049), aminoacyl-tRNA deacylase activity (GO:0002161), Ser-tRNA(Ala) deacylase activity (GO:0002196), alanine-tRNA ligase activity (GO:0004813), ATP binding (GO:0005524), zinc ion binding (GO:0008270), amino acid binding (GO:0016597), peptide lactyltransferase (ATP-dependent) activity (GO:0141207), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), aminoacyl-tRNA ligase activity (GO:0004812), ligase activity (GO:0016874), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
tRNA Aminoacylation	1
Translation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tRNA metabolic process	3
cellular anatomical structure	3
regulation of translational fidelity	2
signal transduction by p53 class mediator	2
catalytic activity, acting on a tRNA	2
binding	2
tRNA processing	1
RNA modification	1
translation	1
tRNA aminoacylation	1
tRNA aminoacylation for protein translation	1
RNA processing	1
cerebellar cortex development	1
anatomical structure development	1
hippo signaling	1
regulation of hippo signaling	1
positive regulation of intracellular signal transduction	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
musculoskeletal movement	1
neuromuscular process	1
apoptotic process	1
regulation of cytoplasmic translational elongation	1
regulation of signal transduction by p53 class mediator	1
negative regulation of intracellular signal transduction	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
signal transduction in response to DNA damage	1
intracellular signal transduction	1
amino acid activation	1
nervous system process	1
RNA binding	1
carboxylic ester hydrolase activity	1
aminoacyl-tRNA metabolism involved in translational fidelity	1

Protein interactions and networks

STRING

2794 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AARS1	KARS1	Q15046	990
AARS1	YARS1	P54577	984
AARS1	YARS2	Q9Y2Z4	920
AARS1	QARS1	P47897	905
AARS1	IARS2	Q9NSE4	904
AARS1	EPRS1	P07814	903
AARS1	RARS2	Q5T160	899
AARS1	TARS3	A2RTX5	895
AARS1	TARS1	P26639	894
AARS1	TARS2	Q9BW92	894
AARS1	AIMP1	Q12904	880
AARS1	LARS2	Q15031	880
AARS1	C9J5N1	C9J5N1	877
AARS1	AARSD1	Q9BTE6	876
AARS1	IARS1	P41252	875

IntAct

80 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
rep	NKRF	psi-mi:“MI:0914”(association)	0.500
AARS1	TIMM44	psi-mi:“MI:0915”(physical association)	0.400
AARS1	SAP18	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
AARS1	YWHAZ	psi-mi:“MI:0915”(physical association)	0.400
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
Calml3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
HSD17B10	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
RAC1	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
ZDHHC5	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
TAGLN	LOC392647	psi-mi:“MI:0914”(association)	0.350
	CLIC1	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
NEK7	SUPT5H	psi-mi:“MI:0914”(association)	0.350
SUZ12	TNPO2	psi-mi:“MI:0914”(association)	0.350
MAPT	SEPTIN8	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (200): AARS (Affinity Capture-RNA), AARS (Affinity Capture-RNA), AARS (Affinity Capture-RNA), AARS (Affinity Capture-MS), AARS (Co-fractionation), AARS (Co-fractionation), AARS (Co-fractionation), GARS (Co-fractionation), IARS (Co-fractionation), MSH2 (Co-fractionation), NMD3 (Co-fractionation), PDIA3 (Co-fractionation), SBDS (Co-fractionation), STAT1 (Co-fractionation), AARS (Affinity Capture-MS)

ESM2 similar proteins: A0A2R6W0K6, F1RQM2, O02606, O15820, O17732, O18719, O50039, O74374, O74478, P12782, P15007, P16243, P26563, P29102, P33401, P36444, P37012, P38628, P39671, P43279, P46248, P47244, P49588, P50475, P52877, P57749, P87144, P93832, Q01637, Q03262, Q09687, Q23919, Q4WY53, Q54UQ2, Q5RC02, Q6K9N6, Q6ZDQ1, Q84LB6, Q8BGQ7, Q8CFX8

Diamond homologs: A1AEN7, A1ATU9, A1AZL6, A1BD33, A1K991, A1V3F2, A1WXK5, A2S3D4, A2SI90, A3MJ36, A3N8K7, A3NUB0, A3PLJ1, A4SGJ6, A4SZL8, A4VJB3, A4WV47, A4XWE2, A5ICV6, A5UY81, A5W0D9, A6H0Y3, A6L1L8, A6LEZ8, A6VA71, A7NQA5, A7ZQC5, A8A3H4, A8ANQ1, A8GA09, A8LL20, A9IK31, B0KR43, B1IUY2, B1JCG9, B1LQ15, B1M0N0, B1XCM5, B1Y1G9, B2U049

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
ATF4	“up-regulates quantity by expression”	AARS1	“transcriptional regulation”
AARS1	“down-regulates quantity”	tRNA(Ala)	“chemical modification”
AARS1	“down-regulates quantity”	alanine	“chemical modification”
AARS1	“up-regulates quantity”	Ala-tRNA(Ala)	“chemical modification”
AARS1	“down-regulates quantity”	ATP(4-)	“chemical modification”
AARS1	“up-regulates quantity”	diphosphate(3-)	“chemical modification”
AARS1	“up-regulates quantity”	AMP	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 96 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transcriptional and post-translational regulation of MITF-M expression and activity	5	14.9×	4e-03
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	12.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1730 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	70
Likely pathogenic	26
Uncertain significance	855
Likely benign	597
Benign	44

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1037702	NM_001605.3(AARS1):c.651del (p.Val218fs)	Pathogenic
1164091	NM_001605.3(AARS1):c.296A>G (p.Glu99Gly)	Pathogenic
1164093	NM_001605.3(AARS1):c.562_563inv (p.Ser188Leu)	Pathogenic
1323796	NM_001605.3(AARS1):c.11_15del (p.Thr4fs)	Pathogenic
1323797	NM_001605.3(AARS1):c.1009G>A (p.Glu337Lys)	Pathogenic
1325386	NM_001605.3(AARS1):c.2067dup (p.Tyr690fs)	Pathogenic
1331693	NM_001605.3(AARS1):c.2702G>A (p.Cys901Tyr)	Pathogenic
146601	GRCh38/hg38 16q21-24.1(chr16:62925929-84585795)x3	Pathogenic
153758	GRCh38/hg38 16q22.1-23.3(chr16:69053457-83274681)x3	Pathogenic
155675	GRCh38/hg38 16q21-23.3(chr16:65957829-83611443)x3	Pathogenic
1676307	GRCh37/hg19 16q11.2-24.3(chr16:46503968-90155062)x3	Pathogenic
1682043	NC_000016.9:g.(?70301542)(70305895_?)del	Pathogenic
1682115	NM_001605.3(AARS1):c.2518C>T (p.Arg840Ter)	Pathogenic
1682195	NM_001605.3(AARS1):c.1792C>T (p.Arg598Ter)	Pathogenic
1682198	NM_001605.3(AARS1):c.1789C>T (p.Arg597Ter)	Pathogenic
1682244	NM_001605.3(AARS1):c.1222G>T (p.Gly408Ter)	Pathogenic
1682286	NM_001605.3(AARS1):c.720_721del (p.Gly241fs)	Pathogenic
1685482	NM_001605.3(AARS1):c.977G>C (p.Arg326Pro)	Pathogenic
1799727	NM_001605.3(AARS1):c.1699C>T (p.Gln567Ter)	Pathogenic
1800083	NM_001605.3(AARS1):c.661C>T (p.Gln221Ter)	Pathogenic
1903181	NM_001605.3(AARS1):c.1032del (p.Phe345fs)	Pathogenic
1934342	NM_001605.3(AARS1):c.1705C>T (p.Arg569Ter)	Pathogenic
1953072	NM_001605.3(AARS1):c.370C>T (p.Gln124Ter)	Pathogenic
1994762	NM_001605.3(AARS1):c.2538_2539delinsTT (p.Lys846_Gln847delinsAsnTer)	Pathogenic
2028990	NM_001605.3(AARS1):c.2324_2325del (p.Ser775fs)	Pathogenic
2043074	NM_001605.3(AARS1):c.1330G>T (p.Glu444Ter)	Pathogenic
2424205	NC_000016.9:g.(?70294927)(70311077_?)del	Pathogenic
2424207	NC_000016.9:g.(?70286624)(70305895_?)del	Pathogenic
2682367	NM_001605.3(AARS1):c.1980dup (p.Glu661Ter)	Pathogenic
2697098	NM_001605.3(AARS1):c.1600_1603del (p.Phe534fs)	Pathogenic

SpliceAI

3599 predictions. Top by Δscore:

Variant	Effect	Δscore
16:70252904:ATTC:A	acceptor_loss	1.0000
16:70252905:TT:T	acceptor_gain	1.0000
16:70252907:C:CC	acceptor_gain	1.0000
16:70252907:C:CG	acceptor_loss	1.0000
16:70253242:T:TA	donor_gain	1.0000
16:70253243:C:A	donor_gain	1.0000
16:70253263:CTGA:C	donor_loss	1.0000
16:70253264:TGAC:T	donor_loss	1.0000
16:70253265:GAC:G	donor_loss	1.0000
16:70253266:A:AG	donor_loss	1.0000
16:70253267:C:T	donor_loss	1.0000
16:70253278:TG:T	donor_gain	1.0000
16:70253278:TGAC:T	donor_gain	1.0000
16:70253298:G:A	donor_gain	1.0000
16:70253382:CT:C	acceptor_loss	1.0000
16:70253383:T:G	acceptor_loss	1.0000
16:70253632:T:TA	donor_gain	1.0000
16:70253718:G:C	donor_gain	1.0000
16:70253797:ACAC:A	acceptor_gain	1.0000
16:70253798:CAC:C	acceptor_gain	1.0000
16:70253798:CACC:C	acceptor_gain	1.0000
16:70253799:ACC:A	acceptor_loss	1.0000
16:70253800:CCT:C	acceptor_loss	1.0000
16:70253801:C:CC	acceptor_gain	1.0000
16:70253802:T:A	acceptor_loss	1.0000
16:70253912:GACTC:G	donor_loss	1.0000
16:70253913:ACTCA:A	donor_loss	1.0000
16:70253914:CT:C	donor_loss	1.0000
16:70253915:TCACT:T	donor_loss	1.0000
16:70253916:CACTC:C	donor_loss	1.0000

AlphaMissense

6371 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:70252873:A:G	W919R	1.000
16:70252873:A:T	W919R	1.000
16:70265614:A:G	L424P	1.000
16:70265629:C:T	G419E	1.000
16:70265630:C:A	G419W	1.000
16:70267715:C:T	G389E	1.000
16:70267735:A:C	F382L	1.000
16:70267735:A:T	F382L	1.000
16:70267737:A:G	F382L	1.000
16:70268357:G:T	R329S	1.000
16:70268367:T:A	R325S	1.000
16:70268367:T:G	R325S	1.000
16:70268368:C:A	R325I	1.000
16:70268368:C:G	R325T	1.000
16:70270291:C:A	G241W	1.000
16:70271813:C:A	E213D	1.000
16:70271813:C:G	E213D	1.000
16:70271814:T:A	E213V	1.000
16:70271924:C:A	W176C	1.000
16:70271924:C:G	W176C	1.000
16:70271926:A:G	W176R	1.000
16:70271926:A:T	W176R	1.000
16:70271930:G:C	N174K	1.000
16:70271930:G:T	N174K	1.000
16:70276999:C:A	M100I	1.000
16:70276999:C:G	M100I	1.000
16:70276999:C:T	M100I	1.000
16:70277000:A:G	M100T	1.000
16:70277005:G:C	F98L	1.000
16:70277005:G:T	F98L	1.000

dbSNP variants (sampled 300 via entrez): RS1000012955 (16:70261794 C>T), RS1000059044 (16:70258324 C>A,G), RS1000072923 (16:70252699 T>C), RS1000185848 (16:70287901 G>C), RS1000335935 (16:70286585 C>G,T), RS1000402983 (16:70251990 G>A,T), RS1000406265 (16:70286362 ATTTTTTTTTTTT>A,AT,ATT,ATTT,ATTTT,ATTTTT,ATTTTTT,ATTTTTTT,ATTTTTTTT,ATTTTTTTTT,ATTTTTTTTTT,ATTTTTTTTTTT,ATTTTTTTTTTTTT,ATTTTTTTTTTTTTT,ATTTTTTTTTTTTTTT,ATTTTTTTTTTTTTTTT,ATTTTTTTTTTTTTTTTT,ATTTTTTTTTTTTTTTTTT,ATTTTTTTTTTTTTTTTTTT,ATTTTTTTTTTTTTTTTTTTT,ATTTTTTTTTTTTTTTTTTTTT,ATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT,ATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT), RS1000462822 (16:70257805 T>A), RS1000559326 (16:70287637 G>A), RS1000568036 (16:70272073 A>C,G), RS1000717047 (16:70261906 C>A,T), RS1000747216 (16:70266663 G>A), RS1000795672 (16:70276287 T>A), RS1000829182 (16:70268122 C>A), RS1000854765 (16:70262094 C>T)

Disease associations

OMIM: gene MIM:601065 | disease phenotypes: MIM:619691, MIM:616339, MIM:613287, MIM:619661, MIM:221820, MIM:118220, MIM:616553, MIM:619649, MIM:119800

GenCC curated gene-disease

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease axonal type 2N	Definitive	Autosomal dominant
undetermined early-onset epileptic encephalopathy	Definitive	Autosomal recessive
developmental and epileptic encephalopathy, 29	Strong	Autosomal recessive
trichothiodystrophy 8, nonphotosensitive	Moderate	Autosomal recessive
leukoencephalopathy, hereditary diffuse, with spheroids 2	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (3)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
AARS1-related leukoencephalopathy	Limited	AD
developmental and epileptic encephalopathy, 29	Definitive	AR
Charcot-Marie-Tooth disease axonal type 2N	Definitive	AD

Mondo (15): Charcot-Marie-Tooth disease type 2 (MONDO:0018993), trichothiodystrophy 8, nonphotosensitive (MONDO:0030517), developmental and epileptic encephalopathy, 29 (MONDO:0014593), Charcot-Marie-Tooth disease axonal type 2N (MONDO:0013212), leukoencephalopathy, hereditary diffuse, with spheroids 2 (MONDO:0030634), leukoencephalopathy, hereditary diffuse, with spheroids (MONDO:0030796), Charcot-Marie-Tooth disease (MONDO:0015626), breast ductal adenocarcinoma (MONDO:0005590), dyskeratosis congenita, autosomal dominant 6 (MONDO:0014690), chromosome 16q12 duplication syndrome (MONDO:0859210), clubfoot (MONDO:0007342), peripheral neuropathy (MONDO:0005244), Charcot-Marie-Tooth disease type 1 (MONDO:0019011), distal hereditary motor neuropathy (MONDO:0018894), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (9): Autosomal dominant Charcot-Marie-Tooth disease type 2 (Orphanet:64746), Non-specific early-onset epileptic encephalopathy (Orphanet:442835), Autosomal dominant Charcot-Marie-Tooth disease type 2N (Orphanet:228174), Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (Orphanet:313808), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Hoyeraal-Hreidarsson syndrome (Orphanet:3322), Familial clubfoot with or without associated lower limb anomalies (Orphanet:199315), Charcot-Marie-Tooth disease type 1 (Orphanet:65753), Distal hereditary motor neuropathy (Orphanet:53739)

HPO phenotypes

189 total (30 of 189 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000133	Gonadal dysgenesis
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000320	Bird-like facies
HP:0000343	Long philtrum
HP:0000348	High forehead
HP:0000407	Sensorineural hearing impairment
HP:0000411	Protruding ear
HP:0000448	Prominent nose
HP:0000482	Microcornea
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000509	Conjunctivitis
HP:0000519	Developmental cataract
HP:0000545	Myopia
HP:0000546	Retinal degeneration
HP:0000565	Esotropia
HP:0000601	Hypotelorism
HP:0000608	Macular degeneration
HP:0000613	Photophobia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010703_100	Brain morphology (MOSTest)	2.000000e-40
GCST010725_47	Malaria	6.000000e-07
GCST010988_47	Adult body size	6.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D003025	Clubfoot	C05.330.488.655.063; C05.330.495.681.063; C05.660.585.512.380.813.063; C16.131.621.585.512.500.681.063
C567653	Charcot-Marie-Tooth Disease, Axonal, Type 2n (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3574 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.43	Kd	3.729	nM	CHEMBL3752910
8.43	ED50	3.729	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 9 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147765: Binding affinity to human AARS incubated for 45 mins by Kinobead based pull down assay	kd	0.0037	uM

CTD chemical–gene interactions

87 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	7
bisphenol A	decreases expression, increases expression, affects expression	6
Tunicamycin	increases expression	6
Cadmium Chloride	decreases expression, increases expression, decreases reaction, increases abundance, increases palmitoylation (+1 more)	5
sodium arsenite	decreases expression, increases expression	4
Benzo(a)pyrene	affects methylation, decreases expression	3
Cisplatin	affects reaction, decreases expression, affects expression	3
perfluorooctane sulfonic acid	increases expression	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	increases expression, decreases expression	2
Cadmium	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
Smoke	decreases expression	2
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
chloroacetaldehyde	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
perfluorooctanoic acid	increases expression	1
ochratoxin A	decreases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
brequinar	increases expression	1
di-n-butylphosphoric acid	affects expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650807	Binding	Binding affinity to human AARS incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

240 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04564430	PHASE4	UNKNOWN	Clonidine for Tourniquet-related Pain in Children
NCT04766684	PHASE4	COMPLETED	Clubfoot Tenotomy Trial
NCT00380965	PHASE4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Chemotherapy-Induced Neuropathy
NCT00487981	PHASE4	TERMINATED	Spinal Cord Stimulation for Painful Diabetic Neuropathy
NCT00904202	PHASE4	COMPLETED	A Study Of Lidocaine Patch 5% Alone, Gabapentin Alone, And Lidocaine Patch 5% And Gabapentin In Combination For The Relief Of Pain In Patients With Diverse Peripheral Neuropathic Pain Conditions
NCT01192113	PHASE4	COMPLETED	Safety and Efficacy of Mecobalamin Injection in Peripheral Neuropathies Patients (Study JGAZSY091109)
NCT01373983	PHASE4	COMPLETED	Intrathecal Bolus Doses of Ziconotide
NCT01458015	PHASE4	TERMINATED	Tapentadol Versus Oxycodone - a Mechanism-based Treatment Approach in Neuropathic Pain
NCT02074267	PHASE4	COMPLETED	Clinical Study for Assessment of the Efficacy of Gabapentin (Carbatin and Neurontin) in Patients With Neuropathy Pain
NCT02372149	PHASE4	UNKNOWN	IVIg for Demyelination in Diabetes Mellitus
NCT02670161	PHASE4	ENROLLING_BY_INVITATION	Quality Improvement and Practice Based Research in Neurology Using the EMR
NCT07022938	PHASE4	COMPLETED	Nutritional Supplement for Treating Chemotherapy Induced Neuropathy
NCT07025005	PHASE4	RECRUITING	Fenofibrate Role in the Prophylaxis From Peripheral Neuropathy Induced by Bortezomib, Lenalidomide and Dexamethasone (VRd) Protocol in the Treatment of Patients With Multiple Myeloma (MM)
NCT04762758	PHASE3	UNKNOWN	Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00058071	PHASE3	COMPLETED	Amifostine in Treating Peripheral Neuropathy in Patients Who Have Received Chemotherapy for Cancer
NCT00125268	PHASE3	TERMINATED	Near Infrared Light for the Treatment of Painful Peripheral Neuropathy
NCT00195013	PHASE3	COMPLETED	Randomized Placebo-Controlled Trial of Glutamine for Breast Cancer Patients With Peripheral Neuropathy
NCT00232141	PHASE3	COMPLETED	Study of Pregabalin Versus Placebo in the Treatment of Nerve Pain Associated With HIV Neuropathy
NCT00264875	PHASE3	COMPLETED	Open Label Safety And Efficacy Study Of Pregabalin In Subjects With Nerve Pain Asociated With Human Immunodeficiency Virus (HIV) Neuropathy
NCT00369564	PHASE3	COMPLETED	Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer
NCT00471445	PHASE3	COMPLETED	Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Cancer Patients
NCT00489411	PHASE3	COMPLETED	Duloxetine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
NCT00710554	PHASE3	COMPLETED	A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia
NCT00711880	PHASE3	COMPLETED	A Study of Sativex® for Relief of Peripheral Neuropathic Pain Associated With Allodynia.
NCT00713323	PHASE3	COMPLETED	A Study to Compare the Safety and Tolerability of Sativex® in Patients With Neuropathic Pain.
NCT00713817	PHASE3	COMPLETED	A Study to Determine the Maintenance of Effect After Long-term Treatment of Sativex® in Subjects With Neuropathic Pain
NCT00775645	PHASE3	COMPLETED	S0715: Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, II, or IIIA Breast Cancer Undergoing Chemo
NCT00872352	PHASE3	UNKNOWN	Evaluation of Bortezomib Induced Peripheral Neuropathy of Multiple Myeloma (MM) Patients
NCT00998738	PHASE3	TERMINATED	Calcium and Magnesium in Preventing Peripheral Neuropathy Caused by Ixabepilone in Patients With Breast Cancer
NCT01049217	PHASE3	TERMINATED	Pregabalin Versus Placebo In The Treatment Of Neuropathic Pain Associated With HIV Neuropathy
NCT01099449	PHASE3	COMPLETED	Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving Oxaliplatin-Based Combination Chemotherapy
NCT01288937	PHASE3	TERMINATED	A Placebo Controlled, Randomized, Double Blind Trial of Milnacipran for the Treatment of Idiopathic Neuropathy Pain
NCT01492920	PHASE3	WITHDRAWN	Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy
NCT01775449	PHASE3	COMPLETED	Prevention of Oxaliplatin-induced Neuropathic Pain by a Specific Diet
NCT02024191	PHASE3	UNKNOWN	The Role of Glutamine for Preventing Oxaliplatin-Induced Peripheral Neuropathy
NCT02217267	PHASE3	COMPLETED	Long Term Outcome After Serial Lidocaine Infusion in Peripheral Neuropathic Pain
NCT02294149	PHASE3	UNKNOWN	Vit D3 and Omega 3 in Chemo Induced Neuropathy
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