YARS1

Summary

YARS1 (tyrosyl-tRNA synthetase 1, HGNC:12840) is a protein-coding gene on chromosome 1p35.1, encoding Tyrosine–tRNA ligase, cytoplasmic (P54577). Tyrosine–tRNA ligase that catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr). It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

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 proteins that appeared in evolution. Tyrosyl-tRNA synthetase belongs to the class I tRNA synthetase family. Cytokine activities have also been observed for the human tyrosyl-tRNA synthetase, after it is split into two parts, an N-terminal fragment that harbors the catalytic site and a C-terminal fragment found only in the mammalian enzyme. The N-terminal fragment is an interleukin-8-like cytokine, whereas the released C-terminal fragment is an EMAP II-like cytokine.

Source: NCBI Gene 8565 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Charcot-Marie-Tooth disease (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 528 total — 7 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 68
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• 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_003680

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12840
Approved symbol	YARS1
Name	tyrosyl-tRNA synthetase 1
Location	1p35.1
Locus type	gene with protein product
Status	Approved
Aliases	YTS, YRS, tyrRS
Ensembl gene	ENSG00000134684
Ensembl biotype	protein_coding
OMIM	603623
Entrez	8565

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 14 protein_coding, 6 retained_intron, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000373477, ENST00000466052, ENST00000469100, ENST00000470377, ENST00000472692, ENST00000478828, ENST00000481895, ENST00000487404, ENST00000490826, ENST00000616261, ENST00000674629, ENST00000674654, ENST00000675785, ENST00000676297, ENST00000906064, ENST00000906065, ENST00000906066, ENST00000906067, ENST00000906068, ENST00000906069, ENST00000918766, ENST00000918767, ENST00000918768, ENST00000918769, ENST00000918770, ENST00000956435

RefSeq mRNA: 1 — MANE Select: NM_003680 NM_003680

CCDS: CCDS368

Canonical transcript exons

ENST00000373477 — 13 exons

Exon	Start	End
ENSE00000916655	32786362	32786447
ENSE00001460665	32817188	32817358
ENSE00003459128	32780085	32780278
ENSE00003465306	32806482	32806611
ENSE00003518261	32782404	32782539
ENSE00003542721	32791162	32791254
ENSE00003543371	32810591	32810766
ENSE00003575922	32779382	32779523
ENSE00003639099	32786940	32787075
ENSE00003674590	32810911	32811057
ENSE00003675832	32797763	32797843
ENSE00003677168	32775239	32776091
ENSE00003691680	32781048	32781145

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 97.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 98.0302 / max 531.8351, expressed in 1828 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11557	93.5247	1828
11558	4.5055	1591

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	97.30	gold quality
right adrenal gland	UBERON:0001233	97.30	gold quality
left adrenal gland	UBERON:0001234	97.14	gold quality
right adrenal gland cortex	UBERON:0035827	97.14	gold quality
prefrontal cortex	UBERON:0000451	97.02	gold quality
endothelial cell	CL:0000115	97.01	gold quality
left adrenal gland cortex	UBERON:0035825	97.01	gold quality
adrenal gland	UBERON:0002369	96.76	gold quality
adrenal cortex	UBERON:0001235	96.66	gold quality
right frontal lobe	UBERON:0002810	96.55	gold quality
cervix squamous epithelium	UBERON:0006922	96.54	gold quality
stromal cell of endometrium	CL:0002255	96.48	gold quality
gingival epithelium	UBERON:0001949	96.40	gold quality
caudate nucleus	UBERON:0001873	96.04	gold quality
frontal cortex	UBERON:0001870	96.00	gold quality
putamen	UBERON:0001874	95.97	gold quality
pancreas	UBERON:0001264	95.93	gold quality
upper lobe of left lung	UBERON:0008952	95.89	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.88	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.84	gold quality
neocortex	UBERON:0001950	95.82	gold quality
upper lobe of lung	UBERON:0008948	95.78	gold quality
cingulate cortex	UBERON:0003027	95.69	gold quality
body of pancreas	UBERON:0001150	95.64	gold quality
anterior cingulate cortex	UBERON:0009835	95.62	gold quality
body of stomach	UBERON:0001161	95.55	gold quality
smooth muscle tissue	UBERON:0001135	95.54	gold quality
gingiva	UBERON:0001828	95.53	gold quality
adrenal tissue	UBERON:0018303	95.45	gold quality
parotid gland	UBERON:0001831	95.39	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	20.64
E-CURD-112	yes	8.71
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting YARS1, 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-3134	100.00	66.43	777
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-1537-5P	98.70	68.33	999
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-6887-5P	98.56	68.49	1295

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 33)

• role in catalyzing tyrosyl-adenylate formation (PMID:11856731)
• replacement of second lysine in KMSKS signature sequence by potassium (PMID:11927599)
• role in inducing angiogenesis (PMID:11956181)
• the KMSSS sequence in human tyrosyl-tRNA synthetase stabilizes the transition state for the tyrosine activation reaction by interacting with the pyrophosphate moiety of ATP (PMID:12016229)
• The recently discovered proangiogenic role of a tyrosyl-tRNA synthetase fragment that stimulates immune cells and links translation to a major cell-signaling pathway is discussed in this review. (PMID:12416978)
• The structure of human mini-TyrRS containing both the catalytic & the anticodon recognition domains, is reported to a resolution of 1.18 A. The spatial disposition of the anticodon recognition domain relative to the catalytic domain is unique. (PMID:12427973)
• identification of two heterozygous missense mutations (G41R and E196K) and one de novo deletion (153-156delVKQV) in tyrosyl-tRNA synthetase (YARS) in three unrelated families affected with dominant intermediate Charcot-Marie-Tooth neuropathy (PMID:16429158)
• Mutating a conserved tyrosine (Y341) that tethers a critical ELR motif in TyrRS resulted in subtle opening of the structure, and activation of cytokine functions, proving the possibility of constitutive gain-of-function mutations in tRNA ligases. (PMID:18096501)
• Human tyrosyl-tRNA synthetase, where a catalytic-domain surface helix, next to the active site, was recruited for interleukin-8-like cytokine signaling. (PMID:19477417)
• Expression of tyrosyl-tRNA synthetase (YARS) DI-CMTC associated mutations (G41R, E196K,153-156delVKQV)in Drosophila leads to neuronal dysfunction. (PMID:19561293)
• Naturally occurring fragments of the two proteins involved in translation, TyrRS and TrpRS, have opposing activities on angiogenesis. (PMID:21442253)
• Dominant Intermediate Charcot-Marie-Tooth disorder is not due to a catalytic defect in tyrosyl-tRNA synthetase. (PMID:21732632)
• Nuclear import of TyrRS is regulated by tRNA(Tyr). (PMID:22291016)
• The full length tyrosyl-tRNA synthetase lacks its cytokine activity because of the interactions between N-terminal and the C-terminal modules, which protect the ELR cytokine motif. (PMID:23334919)
• the association of rare YARS variant with late-onset autosomal dominant Charcot-Marie-Tooth neuropathy (PMID:24354524)
• A major difference between the first- and second-generation tRNA synthetases (RSs) is that the second-generation RSs have an active site more compatible with tyrosine binding. (PMID:24611875)
• This study presents genetic evidence for common mutant-specific interactions between two CMT-associated aminoacyl-tRNA synthetases, lending support for a shared mechanism responsible for the synthetase-induced peripheral neuropathies. (PMID:24807208)
• rhTyrRS promotes migration and aggregation of megakaryocytes to the bone marrow niche (PMID:24907514)
• nuclear-localized TyrRS activates transcription factor E2F1 to upregulate the expression of DNA damage repair genes such as BRCA1 and RAD51. (PMID:25284223)
• Expression of CMT-mutant tyrosyl-tRNA synthetase in Drosophila impairs protein translation. (PMID:26138142)
• Data show that the internal deletion of tyrosyl-tRNA synthetase TyrRSDeltaE2-4 splice variants (SVs) gave an alternative, neomorphic dimer interface ‘orthogonal’ to that of native TyrRS. (PMID:26773056)
• Computational modeling of molecular dynamics of G41R mutant form of human tyrosyl-tRNA synthetase, assosiated with Charcot-Marie-Tooth neuropathy has been presented. (PMID:27025069)
• These YARS variants occur in the catalytic domain and the C-terminal domain, respectively. Mutations in YARS have been previously associated with an autosomal dominant form of Charcot-Marie-Tooth (CMT); our findings suggest the disease spectrum associated with YARS dysregulation is broader than peripheral neuropathy. (PMID:27633801)
• Studied the structural effect of three Charcot-Marie-Tooth disease-causing mutations in tyrosyl-tRNA synthetase. The mutations do not induce changes in protein secondary structures, or shared effects on oligomerization state and stability. However, all mutations provide access to a surface masked in the wild-type enzyme, and that access correlates with protein misinteraction. (PMID:28531329)
• conclusion is further supported by a positive correlation across brain regions between TyrRS expression and arginine-accelerated KTP production. (PMID:29289698)
• Platelet replenishment by YRS(ACT) is independent of thrombopoietin (TPO), as evidenced by expansion of the megakaryocytes from induced pluripotent stem cell-derived hematopoietic stem cells from a patient deficient in TPO signaling. (PMID:30104364)
• Analysis of YARS p.Pro167Thr in yeast complementation assays revealed a loss-of-function, hypomorphic allele that significantly impaired growth. Recombinant YARS p.Pro167Thr demonstrated normal subcellular localization, but greatly diminished ability to homodimerize in human embryonic kidney cells. (PMID:30304524)
• study revealed a new radiation protection mechanism for RSV, in which the acetylation of TyrRS and its translocation into the nucleus is promoted, and this mechanism may also represent a novel protective target against irradiation. (PMID:30939244)
• Moonlighting matrix metalloproteinase substrates: Enhancement of proinflammatory functions of extracellular tyrosyl-tRNA synthetase upon cleavage. (PMID:31771979)
• By revealing the existence of a YARS-PI3K-Akt signaling axis in gastric cancer, we discovered that tRNA synthetase YARS is a novel tumorigenic factor, characterized by its upregulation in tumor-derived specimens, as well as its functions in promoting gastric cancer progression. (PMID:31912229)
• Novel partial loss-of-function variants in the tyrosyl-tRNA synthetase 1 (YARS1) gene involved in multisystem disease. (PMID:34352414)
• The recurrent missense mutation p.(Arg367Trp) in YARS1 causes a distinct neurodevelopmental phenotype. (PMID:34536092)
• Tyrosyl-tRNA synthetase has a noncanonical function in actin bundling. (PMID:36890170)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	yars1	ENSDARG00000035913
mus_musculus	Yars1	ENSMUSG00000028811
rattus_norvegicus	Yars1	ENSRNOG00000007213
drosophila_melanogaster	TyrRS	FBGN0027080

Protein

Protein identifiers

Tyrosine–tRNA ligase, cytoplasmic — P54577 (reviewed: P54577)

Alternative names: Tyrosyl-tRNA synthetase

All UniProt accessions (8): A0A0C4DGZ5, A0A0S2Z4R1, A0A6Q8PF15, A0A6Q8PFC1, A0A6Q8PFX2, A0A6Q8PFX4, A0A6Q8PGW2, P54577

UniProt curated annotations — full annotation on UniProt →

Function. Tyrosine–tRNA ligase that catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr). Also acts as a positive regulator of poly-ADP-ribosylation in the nucleus, independently of its tyrosine–tRNA ligase activity. Activity is switched upon resveratrol-binding: resveratrol strongly inhibits the tyrosine–tRNA ligase activity and promotes relocalization to the nucleus, where YARS1 specifically stimulates the poly-ADP-ribosyltransferase activity of PARP1.

Subunit / interactions. Homodimer. Interacts (when binding to resveratrol) with PARP1; interaction stimulates the poly-ADP-ribosyltransferase activity of PARP1.

Subcellular location. Cytoplasm. Nucleus.

Disease relevance. Charcot-Marie-Tooth disease, dominant intermediate C (CMTDIC) [MIM:608323] A 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. The dominant intermediate type C is characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. The disease is caused by variants affecting the gene represented in this entry. Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2 (IMNEPD2) [MIM:619418] An autosomal recessive disorder with variable clinical manifestations and severity. Main features include cholestatic hepatitis, poor feeding, poor overall growth, and hypoglycemia apparent from infancy. Most patients have variable global developmental delay, sensorineural deafness, retinal abnormalities with visual defects, and hypotonia. Some patients have endocrine abnormalities. Brain imaging often shows dysmyelination, thin corpus callosum, cerebral atrophy, and white matter abnormalities. Death in early childhood may occur. The disease is caused by variants affecting the gene represented in this entry. Defects in YARS1 may be the cause of proximal-predominant motor neuropathy. Affected individuals may develop tremors, cramping of hands, asymmetric weakness in the upper and lower extremities, and present with elevated creatine kinase levels.

Activity regulation. Resveratrol strongly inhibits the tyrosine–tRNA ligase activity.

Domain organisation. The nuclear localization signal, which mediates localization to the nucleus, is also important for interacting with tRNA(Tyr), suggesting that it is sterically blocked when tRNA(Tyr) is bound.

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

RefSeq proteins (1): NP_003671* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002305	aa-tRNA-synth_Ic	Family
IPR002307	Tyr-tRNA-ligase	Family
IPR002547	tRNA-bd_dom	Domain
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR014729	Rossmann-like_a/b/a_fold	Homologous_superfamily
IPR051270

Pfam: PF00579, PF01588

Enzyme classification (BRENDA):

• EC 6.1.1.1 — tyrosine-tRNA ligase (BRENDA: 36 organisms, 102 substrates, 175 inhibitors, 130 Km, 92 kcat entries)

Substrate kinetics (BRENDA)

19 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-TYROSINE	0.0003–1.19	33
TRNATYR	—	25
ATP	0.0004–7	23
TYROSINE	0.002–0.013	5
K+	22–32	4
3-CHLORO-L-TYROSINE	2.04–2.43	2
3-FLUORO-D,L-TYROSINE	0.625–1.3	2
3-IODO-L-TYROSINE	0.13–1.15	2
D-TYROSINE	0.46–14	2
L-3,4-DIHYDROXYPHENYLALANINE	0.56–1.84	2
L-BETA-(5-HYDROXY-2-PYRIDYL)-ALANINE	0.018–0.038	2
TRNACUA	0.0001–0.001	2
TRNATYR(G34C)	0.0007–0.039	2
TRNATYR(WILD-TYPE)	0.0003–0.0014	2
A22G MUTATED TRNATYR TRANSCRIPT	1.6	1

Catalyzed reactions (Rhea), 1 shown:

• tRNA(Tyr) + L-tyrosine + ATP = L-tyrosyl-tRNA(Tyr) + AMP + diphosphate + H(+) (RHEA:10220)

UniProt features (93 total): helix 24, strand 24, sequence variant 10, modified residue 9, binding site 8, turn 6, mutagenesis site 3, short sequence motif 3, chain 2, initiator methionine 1, domain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
1N3L	X-RAY DIFFRACTION	1.18
1Q11	X-RAY DIFFRACTION	1.6
5THL	X-RAY DIFFRACTION	1.6
7ROU	X-RAY DIFFRACTION	1.7
5THH	X-RAY DIFFRACTION	1.96
4Q93	X-RAY DIFFRACTION	2.1
4QBT	X-RAY DIFFRACTION	2.1
1NTG	X-RAY DIFFRACTION	2.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54577-F1	91.12	0.79

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 (8): 166; 170; 170; 173; 173; 188; 39; 39

Post-translational modifications (9): 1, 2, 197, 205, 206, 386, 474, 482, 490

Mutagenesis-validated functional residues (3):

Position	Phenotype
242–247	reduced tyrosine–trna ligase activity.
242–247	slightly reduced tyrosine–trna ligase activity.
242–247	abolished localization to the nucleus. abolished tyrosine–trna ligase activity. abolished ability to activate parp1.

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: 434 (showing top): MORF_DNMT1, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_AMINO_ACID_ACTIVATION, MORF_ESPL1, TSENG_IRS1_TARGETS_UP, MORF_BUB1, GOBP_TRNA_METABOLIC_PROCESS, MAZ_Q6, MORF_RRM1, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, AREB6_01, MORF_HDAC2, CAGCTG_AP4_Q5, GOBP_TRANSLATION, MAYBURD_RESPONSE_TO_L663536_UP

GO Biological Process (7): tyrosyl-tRNA aminoacylation (GO:0006437), apoptotic process (GO:0006915), response to starvation (GO:0042594), translation (GO:0006412), tRNA aminoacylation for protein translation (GO:0006418), response to stress (GO:0006950), protein poly-ADP-ribosylation (GO:0070212)

GO Molecular Function (10): tRNA binding (GO:0000049), RNA binding (GO:0003723), tyrosine-tRNA ligase activity (GO:0004831), interleukin-8 receptor binding (GO:0005153), ATP binding (GO:0005524), small molecule binding (GO:0036094), nucleotide binding (GO:0000166), aminoacyl-tRNA ligase activity (GO:0004812), protein binding (GO:0005515), ligase activity (GO:0016874)

GO Cellular Component (5): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear body (GO:0016604)

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
binding	2
cellular anatomical structure	2
tRNA aminoacylation for protein translation	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
response to stress	1
response to nutrient levels	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
translation	1
tRNA aminoacylation	1
response to stimulus	1
post-translational protein modification	1
RNA binding	1
nucleic acid binding	1
aminoacyl-tRNA ligase activity	1
CXCR chemokine receptor binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
ligase activity, forming carbon-oxygen bonds	1
catalytic activity, acting on a tRNA	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

4475 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
YARS1	WARS1	P23381	991
YARS1	WARS2	Q9UGM6	986
YARS1	AARS1	P49588	984
YARS1	KARS1	Q15046	971
YARS1	GARS1	P41250	964
YARS1	MARS1	P56192	908
YARS1	MARS2	Q96GW9	907
YARS1	QARS1	P47897	881
YARS1	PARS2	Q7L3T8	881
YARS1	IARS2	Q9NSE4	846
YARS1	HARS1	P12081	846
YARS1	IARS1	P41252	846
YARS1	LARS1	Q9P2J5	846
YARS1	LARS2	Q15031	845
YARS1	TARS1	P26639	843

IntAct

122 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HPCAL1	YARS1	psi-mi:“MI:0915”(physical association)	0.560
ZNF20	YARS1	psi-mi:“MI:0915”(physical association)	0.560
COPS3	YARS1	psi-mi:“MI:0915”(physical association)	0.560
PIAS1	YARS1	psi-mi:“MI:0915”(physical association)	0.560
	YARS1	psi-mi:“MI:0915”(physical association)	0.560
SLC27A4	YARS1	psi-mi:“MI:0915”(physical association)	0.560
SPAG8	YARS1	psi-mi:“MI:0915”(physical association)	0.560
GHITM	YARS1	psi-mi:“MI:0915”(physical association)	0.560
ATL1	YARS1	psi-mi:“MI:0915”(physical association)	0.560
MAGEC2	YARS1	psi-mi:“MI:0915”(physical association)	0.560
SLFN12	YARS1	psi-mi:“MI:0915”(physical association)	0.560
CEP70	YARS1	psi-mi:“MI:0915”(physical association)	0.560
CBX2	YARS1	psi-mi:“MI:0915”(physical association)	0.560
TCEAL8	YARS1	psi-mi:“MI:0915”(physical association)	0.560
PACRGL	YARS1	psi-mi:“MI:0915”(physical association)	0.560
ASB9	YARS1	psi-mi:“MI:0915”(physical association)	0.560
ANKRD23	YARS1	psi-mi:“MI:0915”(physical association)	0.560
CCDC158	YARS1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (196): YARS (Affinity Capture-RNA), YARS (Affinity Capture-RNA), YARS (Affinity Capture-RNA), YARS (Affinity Capture-RNA), YARS (Affinity Capture-MS), YARS (Reconstituted Complex), DDB1 (Co-fractionation), EIF1B (Co-fractionation), G3BP2 (Co-fractionation), HNRNPH2 (Co-fractionation), NAA10 (Co-fractionation), NAA15 (Co-fractionation), PROSC (Co-fractionation), TATDN1 (Co-fractionation), YARS (Co-fractionation)

ESM2 similar proteins: E9QI36, F1RQM2, O49299, O80526, O95394, P00949, P08200, P34738, P35494, P36871, P38652, P39126, P39671, P54577, P68209, P93262, P93804, P93805, Q02NB5, Q08DP0, Q13423, Q29465, Q4KM49, Q4R5E4, Q4WY53, Q5R8T5, Q5RFI8, Q5ZJ08, Q5ZJF4, Q6DIJ1, Q6DQL1, Q6TGS6, Q6TWC4, Q7TSV4, Q7ZX51, Q8GTQ9, Q8LAD2, Q96G03, Q9D0F9, Q9M4G4

Diamond homologs: A1RSH9, A2SU89, A3CYG9, A3MXW0, A4WN67, A5UKJ0, A6URQ1, B0R7E0, B6YWK6, B7XHC1, B9LTA6, C3MJP1, C3MYZ9, C3N048, C3N8R2, C3NMQ6, C4KJ87, C4V6W1, C5A5R0, C6A0Z6, F4HWL4, O14055, O27795, O29482, O58739, P36421, P54577, P95982, Q12W06, Q29465, Q2FNA1, Q2NHE1, Q2RHS8, Q3IQU8, Q46BQ5, Q4JCH6, Q4KM49, Q57834, Q5JF63, Q5R8T5

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
QRICH1	“up-regulates quantity by expression”	YARS1	“transcriptional regulation”
ATF4	“up-regulates quantity by expression”	YARS1	“transcriptional regulation”
YARS1	“down-regulates quantity”	tRNA(Tyr)	“chemical modification”
YARS1	“down-regulates quantity”	tyrosine	“chemical modification”
YARS1	“down-regulates quantity”	ATP(4-)	“chemical modification”
YARS1	“up-regulates quantity”	diphosphate(3-)	“chemical modification”
YARS1	“up-regulates quantity”	AMP	“chemical modification”
YARS1	“up-regulates quantity”	Tyr-tRNA(Tyr)	“chemical modification”
YARS1	“up-regulates quantity”	alpha-aminoacyl-tRNA	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	2
Uncertain significance	280
Likely benign	161
Benign	23

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
187863	NM_003680.4(YARS1):c.241_242delinsAT (p.Asp81Ile)	Pathogenic
3191405	NM_003680.4(YARS1):c.159del (p.Phe53fs)	Pathogenic
446531	NM_003680.4(YARS1):c.638C>T (p.Pro213Leu)	Pathogenic
446532	NM_003680.4(YARS1):c.1573G>A (p.Gly525Arg)	Pathogenic
6188	NM_003680.4(YARS1):c.121G>A (p.Gly41Arg)	Pathogenic
6190	NM_003680.4(YARS1):c.458_469del (p.Val153_Val156del)	Pathogenic
625764	GRCh37/hg19 1p35.1-34.3(chr1:32859415-36454915)	Pathogenic
1700208	NM_003680.4(YARS1):c.485G>C (p.Ser162Thr)	Likely pathogenic
4292337	NM_003680.4(YARS1):c.499C>G (p.Pro167Ala)	Likely pathogenic

SpliceAI

2443 predictions. Top by Δscore:

Variant	Effect	Δscore
1:32776088:CAGC:C	acceptor_gain	1.0000
1:32776092:C:CC	acceptor_gain	1.0000
1:32779371:CAG:C	donor_gain	1.0000
1:32779378:TTA:T	donor_loss	1.0000
1:32779379:TA:T	donor_loss	1.0000
1:32779381:C:CG	donor_loss	1.0000
1:32779519:CTTCT:C	acceptor_gain	1.0000
1:32779520:TTCT:T	acceptor_gain	1.0000
1:32779522:CT:C	acceptor_gain	1.0000
1:32779523:TC:T	acceptor_loss	1.0000
1:32779524:C:CC	acceptor_gain	1.0000
1:32780083:A:AC	donor_gain	1.0000
1:32780084:C:CC	donor_gain	1.0000
1:32780128:T:C	donor_gain	1.0000
1:32780283:C:CT	acceptor_gain	1.0000
1:32781044:GTA:G	donor_loss	1.0000
1:32781046:A:C	donor_loss	1.0000
1:32781047:C:CA	donor_loss	1.0000
1:32781146:C:CC	acceptor_gain	1.0000
1:32782368:T:A	donor_gain	1.0000
1:32782402:A:AC	donor_gain	1.0000
1:32782403:C:CC	donor_gain	1.0000
1:32782403:CT:C	donor_gain	1.0000
1:32782403:CTCTG:C	donor_gain	1.0000
1:32782536:CAAC:C	acceptor_gain	1.0000
1:32782540:C:A	acceptor_loss	1.0000
1:32782540:C:CC	acceptor_gain	1.0000
1:32782541:T:A	acceptor_loss	1.0000
1:32786348:T:A	donor_gain	1.0000
1:32786444:AACT:A	acceptor_gain	1.0000

AlphaMissense

3453 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:32791178:A:G	M223T	1.000
1:32797790:C:A	Q188H	1.000
1:32797790:C:G	Q188H	1.000
1:32782427:G:T	A340D	0.999
1:32782516:C:A	K310N	0.999
1:32782516:C:G	K310N	0.999
1:32782520:A:G	L309P	0.999
1:32791174:G:C	S224R	0.999
1:32791174:G:T	S224R	0.999
1:32791176:T:G	S224R	0.999
1:32791177:C:A	M223I	0.999
1:32791177:C:G	M223I	0.999
1:32791177:C:T	M223I	0.999
1:32791178:A:C	M223R	0.999
1:32791180:T:A	K222N	0.999
1:32791180:T:G	K222N	0.999
1:32791196:C:T	G217E	0.999
1:32791202:A:T	V215D	0.999
1:32797787:T:A	R189S	0.999
1:32797787:T:G	R189S	0.999
1:32797788:C:G	R189T	0.999
1:32797803:C:T	G184E	0.999
1:32806486:A:G	L169P	0.999
1:32806496:A:G	Y166H	0.999
1:32806546:C:T	G149E	0.999
1:32806549:G:T	A148D	0.999
1:32806550:C:G	A148P	0.999
1:32806585:A:G	L136P	0.999
1:32810613:C:G	G120R	0.999
1:32810693:C:G	R93P	0.999

dbSNP variants (sampled 300 via entrez): RS1000005241 (1:32810342 A>G), RS1000008745 (1:32803793 G>A,T), RS1000035850 (1:32807697 A>T), RS1000055071 (1:32802791 A>G), RS1000129961 (1:32802980 T>A,C), RS1000193799 (1:32785134 C>A,T), RS1000239920 (1:32796793 A>G), RS1000250595 (1:32791799 T>A), RS1000329027 (1:32789688 A>G), RS1000402586 (1:32790849 G>C), RS1000432757 (1:32798354 T>C), RS1000524397 (1:32798513 G>C), RS1000555702 (1:32798755 C>T), RS1000630467 (1:32814771 C>T), RS1000637315 (1:32778252 G>A)

Disease associations

OMIM: gene MIM:603623 | disease phenotypes: MIM:608323, MIM:616263, MIM:619418, MIM:118220, MIM:256450

GenCC curated gene-disease

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease	Definitive	Autosomal dominant
Charcot-Marie-Tooth disease dominant intermediate C	Strong	Autosomal dominant
neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease	Definitive	AD

Mondo (9): Charcot-Marie-Tooth disease dominant intermediate C (MONDO:0012012), neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset (MONDO:0024189), neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2 (MONDO:0030375), metachromatic leukodystrophy (MONDO:0018868), Charcot-Marie-Tooth disease (MONDO:0015626), anemia (MONDO:0002280), acute kidney injury (MONDO:0002492), hyperinsulinemic hypoglycemia (MONDO:0005803), liver failure (MONDO:0100192)

Orphanet (4): Autosomal dominant intermediate Charcot-Marie-Tooth disease type C (Orphanet:100045), Metachromatic leukodystrophy (Orphanet:512), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Hyperinsulinemic hypoglycaemia (Orphanet:443095)

HPO phenotypes

68 total (30 of 68 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000308	Microretrognathia
HP:0000431	Wide nasal bridge
HP:0000490	Deeply set eye
HP:0000639	Nystagmus
HP:0000662	Nyctalopia
HP:0000786	Primary amenorrhea
HP:0001133	Constriction of peripheral visual field
HP:0001252	Hypotonia
HP:0001274	Agenesis of corpus callosum
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001382	Joint hypermobility
HP:0001394	Cirrhosis
HP:0001397	Hepatic steatosis
HP:0001414	Microvesicular hepatic steatosis
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001531	Failure to thrive in infancy
HP:0001622	Premature birth
HP:0001629	Ventricular septal defect
HP:0001738	Exocrine pancreatic insufficiency
HP:0001744	Splenomegaly
HP:0001747	Accessory spleen
HP:0001748	Polysplenia

GWAS associations

0 associations (top):

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D058186	Acute Kidney Injury	C12.050.351.968.419.780.050; C12.200.777.419.780.050; C12.950.419.780.050
D000740	Anemia	C15.378.050
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
D007966	Leukodystrophy, Metachromatic	C10.228.140.163.100.362.550; C10.228.140.163.100.435.825.850.500; C10.228.140.695.625.550; C10.314.400.550; C16.320.565.189.362.550; C16.320.565.189.435.825.850.500; C16.320.565.398.641.803.925.500; C16.320.565.595.554.825.850.500; C18.452.132.100.362.550; C18.452.132.100.435.825.850.500; C18.452.584.563.641.803.925.500; C18.452.648.189.362.550; C18.452.648.189.435.825.850.500; C18.452.648.398.641.803.925.500; C18.452.648.595.554.825.850.500
D017093	Liver Failure	C06.552.308.500
C564257	Charcot-Marie-Tooth Disease, Dominant Intermediate C (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3179 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 55,106 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL294199	CAPSAICIN	4	52,939
CHEMBL2105728	CRENOLANIB	3	2,167

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

ChEMBL bioactivities

28 potent at pChembl≥5 of 31 total, top 26 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.22	IC50	0.6	nM	CHEMBL310012
9.10	IC50	0.8	nM	CHEMBL163375
8.92	IC50	1.2	nM	CHEMBL51499
8.85	IC50	1.4	nM	CHEMBL1789974
8.70	IC50	2	nM	CHEMBL161302
8.47	IC50	3.4	nM	CHEMBL84867
8.44	IC50	3.6	nM	CHEMBL351127
8.40	IC50	4	nM	CHEMBL163022
7.67	IC50	21.3	nM	CHEMBL52779
7.24	Kd	57.19	nM	CHEMBL5653589
7.24	ED50	57.19	nM	CHEMBL5653589
7.00	IC50	100	nM	CHEMBL422362
6.91	IC50	124	nM	CHEMBL82579
6.80	Kd	156.7	nM	CHEMBL3752910
6.80	ED50	156.7	nM	CHEMBL3752910
6.72	IC50	190	nM	CHEMBL162552
6.61	IC50	245	nM	CHEMBL85201
6.58	IC50	260	nM	CHEMBL159436
6.29	IC50	510	nM	CHEMBL318019
6.10	IC50	800	nM	CHEMBL98455
6.05	IC50	900	nM	CHEMBL98622
5.92	IC50	1200	nM	CHEMBL99347
5.48	Kd	3316	nM	CRENOLANIB
5.47	IC50	3400	nM	CHEMBL95581
5.42	IC50	3800	nM	CHEMBL95286
5.11	IC50	7800	nM	CHEMBL95616

PubChem BioAssay actives

26 with measured affinity, of 279 total; 24 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
(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-[(1S,3S,4S,5R,8R)-2,4,5,8-tetrahydroxy-7-oxa-2-azabicyclo[3.2.1]octan-3-yl]acetic acid	213704: Inhibitory activity against Bacterial Tyrosyl tRNA Synthetase	ic50	0.0006	uM
butyl (2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-methyloxan-2-yl]acetate	213705: Inhibitory activity against Staphylococcus aureus tyrosyl tRNA synthetase (YRS) using aminoacylation assay	ic50	0.0008	uM
(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-[(2S,3S,4S,5S)-1,3,4,5-tetrahydroxypiperidin-2-yl]acetic acid	213707: Inhibitory activity of compound against tyrosyl tRNA synthetase from Staphylococcus aureus was determined	ic50	0.0012	uM
2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-[(1S,3S,4S,5R,8R)-2,4,5,8-tetrahydroxy-7-oxa-2-azabicyclo[3.2.1]octan-3-yl]acetic acid	213707: Inhibitory activity of compound against tyrosyl tRNA synthetase from Staphylococcus aureus was determined	ic50	0.0014	uM
(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-[(1R,5R,8S)-2,4,5,8-tetrahydroxy-7-oxa-2-azabicyclo[3.2.1]octan-3-yl]acetic acid	228645: Inhibitory activity against Staphylococcus aureus tyrosyl tRNA synthetase (YRS) using aminoacylation assay	ic50	0.0020	uM
ethyl (2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-[(1S,4S,5S,6S)-4,5,6-trihydroxycyclohex-2-en-1-yl]acetate	213704: Inhibitory activity against Bacterial Tyrosyl tRNA Synthetase	ic50	0.0034	uM
butyl 2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-[(2R,4R,5R,6R)-4,5-dihydroxy-6-methyloxan-2-yl]acetate	213705: Inhibitory activity against Staphylococcus aureus tyrosyl tRNA synthetase (YRS) using aminoacylation assay	ic50	0.0036	uM
(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-methyloxan-2-yl]acetic acid	213705: Inhibitory activity against Staphylococcus aureus tyrosyl tRNA synthetase (YRS) using aminoacylation assay	ic50	0.0040	uM
(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-[(2S,3S,4S,5S)-1,3,4,5-tetrahydroxypiperidin-2-yl]acetic acid	213707: Inhibitory activity of compound against tyrosyl tRNA synthetase from Staphylococcus aureus was determined	ic50	0.0213	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149794: Binding affinity to human YARS incubated for 45 mins by Kinobead based pull down assay	kd	0.0572	uM
(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-[(2S,3R,4S,5S)-3,4,5-trihydroxyoxan-2-yl]acetic acid	213705: Inhibitory activity against Staphylococcus aureus tyrosyl tRNA synthetase (YRS) using aminoacylation assay	ic50	0.1000	uM
ethyl (2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-[(1S,4S,5S,6S)-4,5,6-trihydroxycyclohex-2-en-1-yl]acetate	213704: Inhibitory activity against Bacterial Tyrosyl tRNA Synthetase	ic50	0.1240	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149794: Binding affinity to human YARS incubated for 45 mins by Kinobead based pull down assay	kd	0.1567	uM
2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-[(2S,3R,4R,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]acetic acid	213705: Inhibitory activity against Staphylococcus aureus tyrosyl tRNA synthetase (YRS) using aminoacylation assay	ic50	0.1900	uM
ethyl (2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-[(1S,2S,3S,4S)-2,3,4-trihydroxycyclohexyl]acetate	213704: Inhibitory activity against Bacterial Tyrosyl tRNA Synthetase	ic50	0.2450	uM
(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-[(2S,3R,4S,5S)-3,4,5-trihydroxyoxan-2-yl]acetic acid	228645: Inhibitory activity against Staphylococcus aureus tyrosyl tRNA synthetase (YRS) using aminoacylation assay	ic50	0.2600	uM
2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-(2,3,4-trihydroxyphenyl)acetic acid	213702: Compound was tested for inhibition of Staphylococcus aureus tyrosyl tRNA Synthetase	ic50	0.5100	uM
2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-(2-hydroxyphenyl)acetic acid	213702: Compound was tested for inhibition of Staphylococcus aureus tyrosyl tRNA Synthetase	ic50	0.8000	uM
(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-phenylacetic acid	213702: Compound was tested for inhibition of Staphylococcus aureus tyrosyl tRNA Synthetase	ic50	0.9000	uM
methyl 2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-(2-hydroxyphenyl)acetate	213702: Compound was tested for inhibition of Staphylococcus aureus tyrosyl tRNA Synthetase	ic50	1.2000	uM
1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine	1425211: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	3.3160	uM
2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-(3-hydroxyphenyl)acetic acid	213702: Compound was tested for inhibition of Staphylococcus aureus tyrosyl tRNA Synthetase	ic50	3.4000	uM
(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid	213702: Compound was tested for inhibition of Staphylococcus aureus tyrosyl tRNA Synthetase	ic50	3.8000	uM
2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-(2-fluorophenyl)acetic acid	213702: Compound was tested for inhibition of Staphylococcus aureus tyrosyl tRNA Synthetase	ic50	7.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	6
bisphenol A	affects expression, decreases expression, increases expression	3
sodium arsenite	affects binding, increases reaction, increases expression	3
perfluorooctanoic acid	increases expression	3
perfluorooctane sulfonic acid	increases expression	3
Cisplatin	affects response to substance, decreases expression	3
Particulate Matter	increases abundance, increases expression, affects cotreatment, affects expression, increases reaction	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
methylmercuric chloride	increases expression	2
ochratoxin A	decreases expression, increases expression, increases methylation	2
mercuric bromide	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
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Estradiol	increases expression	2
Phenobarbital	affects expression, increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tunicamycin	increases expression	2
Valproic Acid	decreases methylation, increases expression	2
Cadmium Chloride	affects localization, increases expression	2
Thapsigargin	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
chloroacetaldehyde	decreases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, affects cotreatment, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1

ChEMBL screening assays

16 unique, capped per target: 16 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991924	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Cellosaurus cell lines

2 cell lines: 2 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A2UY	GM26227	Finite cell line	Female
CVCL_A2UZ	GM26228	Finite cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00003398	PHASE4	COMPLETED	Bone Marrow Transplantation in Treating Patients With Hematologic Cancer
NCT00022386	PHASE4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00046969	PHASE4	COMPLETED	Epoetin Beta in Treating Anemia in Patients With Cervical Cancer
NCT00111995	PHASE4	COMPLETED	Evaluating Aranesp® for the Treatment of Anemia in African-American Subjects With Chronic Renal Failure (CRF) Receiving Hemodialysis
NCT00117039	PHASE4	COMPLETED	A Study to Evaluate the Effectiveness of Aranesp® for Cancer Patients With Anemia
NCT00117065	PHASE4	COMPLETED	Study of Transplant Related Anemia Treated With Aranesp® (STRATA)
NCT00117117	PHASE4	COMPLETED	A Study to Assess Symptom Burden in Subjects With Nonmyeloid Malignancies Receiving Chemotherapy and Aranesp®
NCT00126334	PHASE4	COMPLETED	Conservative Versus Liberal Red Cell Transfusion in Myocardial Infarction Trial: The CRIT Pilot
NCT00153868	PHASE4	COMPLETED	A Web-based Study of Quality of Life Benefits Associated Aranesp in Anemic Patients With Cancer
NCT00168948	PHASE4	UNKNOWN	Intermittent Antimalaria Treatment With SP in African Children
NCT00173706	PHASE4	UNKNOWN	Evaluation of the Effects of L-Carnitine Injection in Patients Undergoing Hemodialysis
NCT00194857	PHASE4	TERMINATED	Treatment of Anemia and Neutropenia in HIV/HCV Coinfected Patients Treated With Pegylated Interferon and Ribavirin
NCT00204334	PHASE4	COMPLETED	Effects of Anemia Correction on Vascular and Monocyte Function in Renal Transplant Recipients
NCT00206739	PHASE4	COMPLETED	Intermittent Treatment With Sulfadoxine-pyrimethamine for Malaria Control in Infants
NCT00211120	PHASE4	TERMINATED	Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR)
NCT00216541	PHASE4	COMPLETED	A Study of the Safety and Effectiveness of Epoetin Alfa on Hemoglobin Levels and Blood Transfusions in Cancer Patients Receiving Chemotherapy
NCT00223938	PHASE4	TERMINATED	Study of the Efficacy and Safety of Ferrlecit in the Maintenance Dosing in Hemodialysis Patients.
NCT00223964	PHASE4	COMPLETED	Study of the Efficacy of Two Doses of Ferrlecit in the Treatment of Iron Deficiency in Pediatric Hemodialysis Patients
NCT00224003	PHASE4	COMPLETED	Study of the Safety and Efficacy of Ferrlecit® Maintenance Dosing in Pediatric Hemodialysis Patients
NCT00224068	PHASE4	COMPLETED	Effect of Iron Therapy as an Adjunct to Epoetin Alfa in the Anemia of Cancer Chemotherapy
NCT00239642	PHASE4	COMPLETED	Safety and Efficacy of Iron Sucrose in Children
NCT00247507	PHASE4	UNKNOWN	The Effects of Acetylcysteine on Alleviating Damage of Oxidative Stress in Hemodialysis Patients
NCT00248716	PHASE4	UNKNOWN	Treatment of Anemia in the 2nd Year of Life. Comparison of the Efficacy of Two Different Iron Preparations.
NCT00283465	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Treatment With Epoetin Alfa on Hemoglobin Levels, Red Blood Cell Transfusions, and Quality of Life in Patients With Cancer Receiving Platinum-containing Chemotherapy
NCT00312871	PHASE4	TERMINATED	Effects of Early Correction of Anemia in Patients With Chronic Renal Insufficiency
NCT00315484	PHASE4	COMPLETED	Hematologic Response of Epoetin Alfa (PROCRIT) Versus Darbepoetin Alfa (ARANESP) in Chemotherapy Induced Anemia
NCT00317902	PHASE4	COMPLETED	An Open-Label Study to Evaluate the Effect of Every Other Week PROCRIT� (Epoetin Alfa) Dosing (40,000-60,000 Units) On Maintaining Quality of Life and Target Hemoglobin Levels in Anemic HIV-Infected Patients (CHAMPS II)
NCT00335023	PHASE4	COMPLETED	Well Being of Obstetric Patients on Minimal Blood Transfusions
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00377481	PHASE4	COMPLETED	COMFORT Study: A Crossover Study of NeoRecormon (Epoetin Beta) and Darbepoetin Alfa in Patients With Renal Anemia.
NCT00396435	PHASE4	COMPLETED	Correction of Anaemia and Progression of Renal Failure on Transplanted Patients
NCT00401869	PHASE4	COMPLETED	The Effect of PROCRIT (Epoetin Alfa) on Postoperative Vigor and Handgrip Strength (VIGOR Study)
NCT00413101	PHASE4	COMPLETED	A Study of NeoRecormon (Epoetin Beta) in Patients With End Stage Renal Disease.
NCT00431496	PHASE4	COMPLETED	A Study of Cinacalcet to Improve Achievement of National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) Targets in Patients With End Stage Renal Disease (ESRD)
NCT00437723	PHASE4	COMPLETED	A Study of NeoRecormon in Patients With Chronic Kidney Disease.
NCT00440063	PHASE4	TERMINATED	A Study of NeoRecormon (Epoetin Beta) in Patients With Renal Anemia.
NCT00470158	PHASE4	COMPLETED	Delivery of Iron and Zinc Supplements: Evaluation of Interaction Effect on Biochemical and Clinical Outcomes
NCT00479102	PHASE4	UNKNOWN	Prevention of Iron Deficiency in 2nd Year of Life
NCT00495365	PHASE4	TERMINATED	A Dose Conversion Study of Epoetin Alfa in Subjects With the Anemia of Chronic Kidney Disease.
NCT00495378	PHASE4	TERMINATED	RAPID-2. A Study to Evaluate the Effectiveness of Alternate Dosing of PROCRIT (Epoetin Alfa) in Maintaining Hemoglobin Levels in Patients With Chemotherapy Related Anemia