EPRS1

Summary

EPRS1 (glutamyl-prolyl-tRNA synthetase 1, HGNC:3418) is a protein-coding gene on chromosome 1q41, encoding Bifunctional glutamate/proline–tRNA ligase (P07814). Multifunctional protein which primarily functions within the aminoacyl-tRNA synthetase multienzyme complex, also known as multisynthetase complex. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. The protein encoded by this gene is a multifunctional aminoacyl-tRNA synthetase that catalyzes the aminoacylation of glutamic acid and proline tRNA species. Alternative splicing has been observed for this gene, but the full-length nature and biological validity of the variant have not been determined.

Source: NCBI Gene 2058 — RefSeq curated summary.

At a glance

• Gene–disease (curated): leukodystrophy, hypomyelinating, 15 (Strong, GenCC)
• GWAS associations: 24
• Clinical variants (ClinVar): 535 total — 16 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 38
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_004446

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3418
Approved symbol	EPRS1
Name	glutamyl-prolyl-tRNA synthetase 1
Location	1q41
Locus type	gene with protein product
Status	Approved
Aliases	EARS, PARS, GLUPRORS
Ensembl gene	ENSG00000136628
Ensembl biotype	protein_coding
OMIM	138295
Entrez	2058

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000366923, ENST00000464052, ENST00000468487, ENST00000477030, ENST00000485821, ENST00000609181, ENST00000927910, ENST00000927911, ENST00000927912, ENST00000927913, ENST00000927914, ENST00000927915, ENST00000927916, ENST00000952426

RefSeq mRNA: 1 — MANE Select: NM_004446 NM_004446

CCDS: CCDS31027

Canonical transcript exons

ENST00000366923 — 32 exons

Exon	Start	End
ENSE00000925588	219988590	219988823
ENSE00000925589	219996983	219997342
ENSE00000925594	220010946	220011056
ENSE00000925595	220018449	220018508
ENSE00000925596	220018995	220019079
ENSE00000925597	220019988	220020221
ENSE00000925598	220022347	220022518
ENSE00000925599	220024264	220024456
ENSE00001127050	220007202	220007338
ENSE00001127090	220025132	220025258
ENSE00001127099	220030386	220030480
ENSE00001127104	220032387	220032526
ENSE00001129041	220033502	220033658
ENSE00001443000	220046343	220046505
ENSE00001710859	219968600	219968956
ENSE00002327309	219979418	219979615
ENSE00002343965	219972069	219972147
ENSE00002353014	219980756	219980857
ENSE00002358501	219982772	219982844
ENSE00002360510	219980085	219980240
ENSE00002377392	219969058	219969122
ENSE00002386660	219981378	219981457
ENSE00002390437	219973238	219973398
ENSE00002410141	219984206	219984257
ENSE00002417673	219978546	219978719
ENSE00002712566	219987142	219987404
ENSE00003478317	219983189	219983398
ENSE00003485114	220005248	220005360
ENSE00003505749	220006106	220006313
ENSE00003583570	220001138	220001255
ENSE00003703985	220040185	220040269
ENSE00003711245	220034914	220035013

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 64.3506 / max 1285.2682, expressed in 1823 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17543	60.6541	1823
17544	1.9916	1018
17542	1.0855	637
17545	0.6193	365

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	98.87	gold quality
cranial nerve II	UBERON:0000941	97.44	gold quality
cortical plate	UBERON:0005343	97.21	gold quality
secondary oocyte	CL:0000655	97.19	gold quality
calcaneal tendon	UBERON:0003701	97.10	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.89	gold quality
ventricular zone	UBERON:0003053	96.78	gold quality
tibia	UBERON:0000979	96.77	gold quality
islet of Langerhans	UBERON:0000006	96.76	gold quality
tendon	UBERON:0000043	96.56	gold quality
lateral globus pallidus	UBERON:0002476	96.56	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.54	gold quality
medial globus pallidus	UBERON:0002477	96.40	gold quality
middle temporal gyrus	UBERON:0002771	96.34	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.29	gold quality
globus pallidus	UBERON:0001875	96.24	gold quality
tendon of biceps brachii	UBERON:0008188	96.18	gold quality
body of pancreas	UBERON:0001150	96.15	gold quality
pancreas	UBERON:0001264	96.07	gold quality
oocyte	CL:0000023	95.87	gold quality
pylorus	UBERON:0001166	95.74	gold quality
superior surface of tongue	UBERON:0007371	95.74	gold quality
mucosa of transverse colon	UBERON:0004991	95.69	gold quality
substantia nigra pars compacta	UBERON:0001965	95.67	gold quality
primary visual cortex	UBERON:0002436	95.64	gold quality
pituitary gland	UBERON:0000007	95.57	gold quality
inferior olivary complex	UBERON:0002127	95.55	gold quality
adenohypophysis	UBERON:0002196	95.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.50	gold quality
corpus callosum	UBERON:0002336	95.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

28 targeting EPRS1, 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-548C-3P	99.99	74.01	7587
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-3164	99.02	68.39	1071
HSA-MIR-6820-3P	99.02	68.50	1035
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-5000-5P	97.40	66.11	1055
HSA-MIR-3200-5P	97.34	65.97	826
HSA-MIR-424-3P	97.20	65.86	385
HSA-MIR-548AD-3P	94.39	66.04	350
HSA-MIR-553	94.01	65.93	158

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 14)

• Results show that glutamyl-prolyl-tRNA synthetase has a regulated, noncanonical activity that blocks synthesis of a specific protein. (PMID:15479637)
• Essentiality of this enzyme’s domains in its noncanonical function of regulating inflammatory gene expression. (PMID:18374644)
• EPRS phosphorylation events regulate GAIT-mediated gene silencing. (PMID:19647514)
• Study reveals a unique role of Cdk5/p35 in activation of the major noncanonical function of EPRS, namely translational control of macrophage inflammatory gene expression. (PMID:21220307)
• Dynamic model simulations predicted an inhibitory GAIT-element-interacting factor to account for this relationship and led to the identification of a truncated form of EPRS, a GAIT constituent that mediates binding to target transcripts. (PMID:22386318)
• analysis of the heterotetrameric complex structure of the glutathione transferase (GST) domains shared among the four MSC components, methionyl-tRNA synthetase (MRS), glutaminyl-prolyl-tRNA synthetase (EPRS), AIMP2 and AIMP3 (PMID:26472928)
• Data indicate the necessity of EPRS for proliferation of tamoxifen-resistant estrogen receptor (ER+) breast cancer, but not ER- breast cancer cells. (PMID:27612429)
• five different EPRS mutations were identified. (PMID:29576217)
• The human glutamyl-prolyl-tRNA synthetase (EPRS) consisting of two fused synthetases .This study identified site-selective proteolysis as a mechanism that severs the linkage between the EPRS synthetases in vitro and in vivo Caspase action targeted Asp-929 in the third WHEP domain, thereby separating the two synthetases. (PMID:29643180)
• Glutamyl-Prolyl-tRNA Synthetase Regulates Proline-Rich Pro-Fibrotic Protein Synthesis During Cardiac Fibrosis. (PMID:32611237)
• Disease-associated mutations in a bifunctional aminoacyl-tRNA synthetase gene elicit the integrated stress response. (PMID:34537243)
• Prolyl-tRNA synthetase as a novel therapeutic target in multiple myeloma. (PMID:36631435)
• Glutamyl-prolyl-tRNA synthetase (EPRS1) drives tubulointerstitial nephritis-induced fibrosis by enhancing T cell proliferation and activity. (PMID:38320721)
• Homozygous EPRS1 missense variant causing hypomyelinating leukodystrophy-15 alters variant-distal mRNA m[6]A site accessibility. (PMID:38769304)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eprs1	ENSDARG00000060494
mus_musculus	Eprs1	ENSMUSG00000026615
rattus_norvegicus	Eprs1	ENSRNOG00000002393
drosophila_melanogaster	GluProRS	FBGN0005674
caenorhabditis_elegans	ears-1	WBGENE00001337

Paralogs (2): EARS2 (ENSG00000103356), QARS1 (ENSG00000172053)

Protein

Protein identifiers

Bifunctional glutamate/proline–tRNA ligase — P07814 (reviewed: P07814)

Alternative names: Bifunctional aminoacyl-tRNA synthetase, Cell proliferation-inducing gene 32 protein, Glutamatyl-prolyl-tRNA synthetase

All UniProt accessions (3): P07814, V9GYZ6, V9GZ76

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional protein which primarily functions within the aminoacyl-tRNA synthetase multienzyme complex, also known as multisynthetase complex. Within the complex it catalyzes the attachment of both L-glutamate and L-proline to their cognate tRNAs in a two-step reaction where the amino acid is first activated by ATP to form a covalent intermediate with AMP. Subsequently, the activated amino acid is transferred to the acceptor end of the cognate tRNA to form L-glutamyl-tRNA(Glu) and L-prolyl-tRNA(Pro). Upon interferon-gamma stimulation, EPRS1 undergoes phosphorylation, causing its dissociation from the aminoacyl-tRNA synthetase multienzyme complex. It is recruited to form the GAIT complex, which binds to stem loop-containing GAIT elements found in the 3’-UTR of various inflammatory mRNAs, such as ceruloplasmin. The GAIT complex inhibits the translation of these mRNAs, allowing interferon-gamma to redirect the function of EPRS1 from protein synthesis to translation inhibition in specific cell contexts. Furthermore, it can function as a downstream effector in the mTORC1 signaling pathway, by promoting the translocation of SLC27A1 from the cytoplasm to the plasma membrane where it mediates the uptake of long-chain fatty acid by adipocytes. Thereby, EPRS1 also plays a role in fat metabolism and more indirectly influences lifespan.

Subunit / interactions. Homodimer. Part of the aminoacyl-tRNA synthetase multienzyme complex, also know as multisynthetase complex (MSC), that is composed of the tRNA ligases for Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys (KARS1), Met (MARS1) the bifunctional ligase for Glu and Pro (EPRS1) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18. Forms a linear complex that contains MARS1, EEF1E1, EPRS1 and AIMP2 that is at the core of the multisubunit complex. Interacts with TARS3. Interacts with DUS2L. Component of the GAIT complex which is composed of EPRS1, RPL13A and GAPDH. For human, the complex assembly seems to be a two-step process in which EPRS1 first associates with SYNCRIP to form a pre-GAIT complex which is deficient in GAIT element binding. Interacts (phosphorylated at Ser-999) with SLC27A1; mediates the translocation of SLC27A1 from the cytoplasm to the plasma membrane thereby increasing the uptake of long-chain fatty acids.

Subcellular location. Cytoplasm. Cytosol. Membrane.

Post-translational modifications. Phosphorylated at Ser-886 by CDK5. Phosphorylated at Ser-999 by RPS6KB1; triggers EPRS1 release from the aminoacyl-tRNA synthetase multienzyme complex. In monocytes, the IFN-gamma-induced sequential phosphorylation at Ser-886 and Ser-999 releases EPRS1 from the aminoacyl-tRNA synthetase multienzyme complex, allowing its association with the GAIT complex. Phosphorylation at Ser-999 is specifically required for the RPL13A-mediated interaction of the GAIT complex with eIF4G. Phosphorylation at Ser-999 by RPS6KB1, is also induced by insulin through activation of the mTORC1 signaling pathway and promotes the interaction of EPRS1 with SLC27A1.

Disease relevance. Leukodystrophy, hypomyelinating, 15 (HLD15) [MIM:617951] An autosomal recessive disorder characterized by hypomyelinating leukodystrophy with thinning of the corpus callosum. Clinical features include motor and cognitive impairment appearing in the first or second decade of life, dystonia, ataxia, spasticity, and dysphagia. Most patients develop severe optic atrophy, and some have hearing loss. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by halofuginone. Can be activated by azetidine-2-carboxylic acid (Aze), a non-proteinogenic amino acids found in plants that mimics both proline and alanine, leading to misincorporation of Aze into proline positions of proteins.

Domain organisation. The WHEP-TRS domains are involved in RNA binding.

Similarity. In the N-terminal section; belongs to the class-I aminoacyl-tRNA synthetase family. Glutamate–tRNA ligase type 2 subfamily. In the C-terminal section; belongs to the class-II aminoacyl-tRNA synthetase family.

RefSeq proteins (1): NP_004437* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000738	WHEP-TRS_dom	Domain
IPR000924	Glu/Gln-tRNA-synth	Family
IPR001412	aa-tRNA-synth_I_CS	Conserved_site
IPR002314	aa-tRNA-synt_IIb	Domain
IPR004154	Anticodon-bd	Domain
IPR004499	Pro-tRNA-ligase_IIa_arc-type	Family
IPR004526	Glu-tRNA-synth_arc/euk	Family
IPR006195	aa-tRNA-synth_II	Domain
IPR009068	uS15_NS1_RNA-bd_sf	Homologous_superfamily
IPR011035	Ribosomal_bL25/Gln-tRNA_synth	Homologous_superfamily
IPR014729	Rossmann-like_a/b/a_fold	Homologous_superfamily
IPR016061	Pro-tRNA_ligase_II_C	Domain
IPR017449	Pro-tRNA_synth_II	Homologous_superfamily
IPR020056	Rbsml_bL25/Gln-tRNA_synth_N	Homologous_superfamily
IPR020058	Glu/Gln-tRNA-synth_Ib_cat-dom	Domain
IPR020059	Glu/Gln-tRNA-synth_Ib_codon-bd	Domain
IPR033721	ProRS_core_arch_euk	Domain
IPR036282	Glutathione-S-Trfase_C_sf	Homologous_superfamily
IPR036621	Anticodon-bd_dom_sf	Homologous_superfamily
IPR045864	aa-tRNA-synth_II/BPL/LPL	Homologous_superfamily
IPR049437	tRNA-synt_1c_C2	Domain
IPR053836	Arc1-like_N	Domain

Pfam: PF00458, PF00587, PF00749, PF03129, PF03950, PF09180, PF20974, PF21972

Enzyme classification (BRENDA):

• EC 6.1.1.15 — proline-tRNA ligase (BRENDA: 46 organisms, 163 substrates, 155 inhibitors, 127 Km, 85 kcat entries)
• EC 6.1.1.17 — glutamate-tRNA ligase (BRENDA: 44 organisms, 91 substrates, 48 inhibitors, 66 Km, 31 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
L-PROLINE	0.0046–50	46
TRNAGLU	—	19
L-CYSTEINE	0.01–0.26	14
ATP	0.0024–0.32	12
TRNAPRO	—	10
GLU	0.0023–3	8
3,4-DEHYDRO-DL-PROLINE	0.28–2.2	7
PRO	0.12–3.1	7
L-ALANINE	79–1360	6
L-PRO	0.137–0.625	6
N-METHYLGLYCINE	45–300	5
ATP	0.049–0.6	4
L-AZETIDINE-2-CARBOXYLIC ACID	1.43–5.3	3
L-GLUTAMATE	0.0014–20	3
TRNAGLN	0.0001–0.0017	3

Catalyzed reactions (Rhea), 2 shown:

• tRNA(Pro) + L-proline + ATP = L-prolyl-tRNA(Pro) + AMP + diphosphate (RHEA:14305)
• tRNA(Glu) + L-glutamate + ATP = L-glutamyl-tRNA(Glu) + AMP + diphosphate (RHEA:23540)

UniProt features (155 total): strand 35, helix 29, modified residue 24, binding site 16, sequence variant 12, turn 10, mutagenesis site 8, region of interest 6, sequence conflict 5, compositionally biased region 4, domain 3, short sequence motif 2, chain 1

Structure

Experimental structures (PDB)

33 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7X09	X-RAY DIFFRACTION	1.7
7F99	X-RAY DIFFRACTION	1.98
7Y1H	X-RAY DIFFRACTION	1.99
7F9B	X-RAY DIFFRACTION	2
7F98	X-RAY DIFFRACTION	2
7F9A	X-RAY DIFFRACTION	2
4HVC	X-RAY DIFFRACTION	2
7X1O	X-RAY DIFFRACTION	2.04
5A1N	X-RAY DIFFRACTION	2.1
7BBU	X-RAY DIFFRACTION	2.19
7F9C	X-RAY DIFFRACTION	2.2
7OSY	X-RAY DIFFRACTION	2.23
7Y28	X-RAY DIFFRACTION	2.29
4K87	X-RAY DIFFRACTION	2.3
5A5H	X-RAY DIFFRACTION	2.32
7OT0	X-RAY DIFFRACTION	2.32
5VAD	X-RAY DIFFRACTION	2.36
4K86	X-RAY DIFFRACTION	2.4
7OSZ	X-RAY DIFFRACTION	2.46
7OT2	X-RAY DIFFRACTION	2.48
7F9D	X-RAY DIFFRACTION	2.5
7Y1W	X-RAY DIFFRACTION	2.5
7OT3	X-RAY DIFFRACTION	2.53
8YTK	X-RAY DIFFRACTION	2.55
5V58	X-RAY DIFFRACTION	2.59
5A34	X-RAY DIFFRACTION	2.6
5BMU	X-RAY DIFFRACTION	2.6
7Y3S	X-RAY DIFFRACTION	2.6
4K88	X-RAY DIFFRACTION	2.62
7OT1	X-RAY DIFFRACTION	2.71

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07814-F1	83.55	0.53

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 (16): 1121–1123; 1152; 1152; 1154; 1163; 1164; 1237; 1237; 1240; 1242; 1276; 1278 …

Post-translational modifications (24): 300, 300, 355, 417, 434, 498, 535, 542, 637, 747, 788, 861, 872, 882, 885, 886, 891, 898, 998, 999 …

Mutagenesis-validated functional residues (8):

Position	Phenotype
886	abolishes release from the aminoacyl-trna synthetase multienzyme complex and association with the gait complex upon inte
886	not active in translation inhibition (phosphomimetic) and abolishes gait complex association with eif4g. no effect on in
999	not active in translation inhibition, abolishes release from the aminoacyl-trna synthetase multienzyme complex and assoc
999	active in translation inhibition (phosphomimetic). no effect on gait complex association with eif4g.
1097	almost complete loss of prolyl-trna ligase activity.
1097	no effect on prolyl-trna ligase activity. decreases inhibition by halofuginone.
1152	no effect on prolyl-trna ligase activity. decreases inhibition by halofuginone.
1152	almost complete loss of prolyl-trna ligase activity.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-2408522	Selenoamino acid metabolism
R-HSA-379716	Cytosolic tRNA aminoacylation
R-HSA-6782315	tRNA modification in the nucleus and cytosol
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-379724	tRNA Aminoacylation
R-HSA-392499	Metabolism of proteins
R-HSA-71291	Metabolism of amino acids and derivatives
R-HSA-72306	tRNA processing
R-HSA-72766	Translation
R-HSA-8953854	Metabolism of RNA
R-HSA-9730414	MITF-M-regulated melanocyte development

MSigDB gene sets: 476 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_AMINO_ACID_ACTIVATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, GOBP_RESPONSE_TO_PEPTIDE, SHEPARD_CRASH_AND_BURN_MUTANT_UP, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GCM_NPM1, GOBP_TRNA_METABOLIC_PROCESS, MITSIADES_RESPONSE_TO_APLIDIN_DN

GO Biological Process (11): tRNA aminoacylation for protein translation (GO:0006418), glutamyl-tRNA aminoacylation (GO:0006424), prolyl-tRNA aminoacylation (GO:0006433), negative regulation of translation (GO:0017148), cellular response to insulin stimulus (GO:0032869), cellular response to type II interferon (GO:0071346), regulation of long-chain fatty acid import into cell (GO:0140212), translation (GO:0006412), regulation of translation (GO:0006417), tRNA aminoacylation (GO:0043039), positive regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043517)

GO Molecular Function (15): glutamate-tRNA ligase activity (GO:0004818), proline-tRNA ligase activity (GO:0004827), ATP binding (GO:0005524), zinc ion binding (GO:0008270), RNA stem-loop binding (GO:0035613), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), GTPase binding (GO:0051020), nucleotide binding (GO:0000166), RNA binding (GO:0003723), catalytic activity (GO:0003824), aminoacyl-tRNA ligase activity (GO:0004812), protein binding (GO:0005515), ligase activity (GO:0016874), metal ion binding (GO:0046872)

GO Cellular Component (9): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), aminoacyl-tRNA synthetase multienzyme complex (GO:0017101), sperm midpiece (GO:0097225), GAIT complex (GO:0097452), ribonucleoprotein complex (GO:1990904), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
tRNA Aminoacylation	1
tRNA processing	1
MITF-M-regulated melanocyte development	1
Translation	1
Metabolism	1
Metabolism of RNA	1
Metabolism of proteins	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
translation	3
tRNA aminoacylation for protein translation	2
aminoacyl-tRNA ligase activity	2
protein-containing complex	2
tRNA aminoacylation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
response to insulin	1
cellular response to peptide hormone stimulus	1
response to type II interferon	1
cellular response to cytokine stimulus	1
long-chain fatty acid import into cell	1
regulation of fatty acid transport	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
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
tRNA metabolic process	1
amino acid activation	1
DNA damage response, signal transduction by p53 class mediator	1
regulation of DNA damage response, signal transduction by p53 class mediator	1
positive regulation of signal transduction by p53 class mediator	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
RNA binding	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
enzyme binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid binding	1

Protein interactions and networks

STRING

6880 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPRS1	RPL13A	P40429	997
EPRS1	SYNCRIP	O60506	995
EPRS1	GAPDH	P00354	994
EPRS1	IARS1	P41252	993
EPRS1	PARS2	Q7L3T8	993
EPRS1	KARS1	Q15046	992
EPRS1	MARS1	P56192	990
EPRS1	RARS2	Q5T160	988
EPRS1	LARS1	Q9P2J5	984
EPRS1	RARS1	P54136	976
EPRS1	MARS2	Q96GW9	975
EPRS1	LARS2	Q15031	973
EPRS1	MRPL13	Q9BYD1	966
EPRS1	IARS2	Q9NSE4	966
EPRS1	F10	P00742	940

IntAct

244 interactions, top by confidence:

A	B	Type	Score
EPRS1	IARS1	psi-mi:“MI:0915”(physical association)	0.880
IARS1	EPRS1	psi-mi:“MI:0915”(physical association)	0.880
IARS1	EPRS1	psi-mi:“MI:0407”(direct interaction)	0.880
EPRS1	KARS1	psi-mi:“MI:0915”(physical association)	0.720
KARS1	EPRS1	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HSCB	EPRS1	psi-mi:“MI:0914”(association)	0.670
HSCB	EPRS1	psi-mi:“MI:0915”(physical association)	0.670
EPRS1	RARS1	psi-mi:“MI:0915”(physical association)	0.660
EPRS1	SYNCRIP	psi-mi:“MI:0915”(physical association)	0.640
EPRS1	SYNCRIP	psi-mi:“MI:0914”(association)	0.640
EPRS1	EPRS1	psi-mi:“MI:0407”(direct interaction)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
QARS1	EEF1E1	psi-mi:“MI:0914”(association)	0.530
SDCBP	TARS3	psi-mi:“MI:0914”(association)	0.530
COMTD1	IFRD1	psi-mi:“MI:0914”(association)	0.530
NCAPD3	EPRS1	psi-mi:“MI:0915”(physical association)	0.500
EPRS1	NCAPD3	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (651): EPRS (Affinity Capture-MS), EPRS (Affinity Capture-RNA), EPRS (Affinity Capture-MS), EPRS (Affinity Capture-MS), EPRS (Affinity Capture-MS), EPRS (Affinity Capture-MS), EPRS (Affinity Capture-MS), EPRS (Reconstituted Complex), EPRS (Affinity Capture-MS), EPRS (Affinity Capture-MS), EPRS (Affinity Capture-MS), AIMP1 (Co-fractionation), AIMP2 (Co-fractionation), ATAD3B (Co-fractionation), CANX (Co-fractionation)

ESM2 similar proteins: A0A224AHH8, A0A3S6I186, A0A5C1J0Z8, A0A6B9KZ52, A0A6I8TMQ9, A1L015, A1L017, A1L018, B1P1J3, B2Z449, B7PKZ1, B7PKZ2, D0NBV1, D0NBV3, D0NBV4, D0NP95, G5EGI7, J7MAN2, J7MFT5, P01039, P07814, P0CU39, P0CU40, P0CU41, P0CU42, P0DXA0, P20690, P22085, P23779, P31726, P31727, P35173, P35174, P35175, P48735, P54071, P54364, P56574, P90698, Q04467

Diamond homologs: A0B966, A0RY20, A1RRG7, A1RYD7, A2BK91, A2SRG2, A3CWJ3, A3DMR5, A3MV95, A4FXG8, A4SZM1, A4WKI4, A4YIL8, A5N6Y3, A5UN79, A6UP25, A6UW15, A6VFU7, A6VP11, A7IAG1, A8ABI5, A8AJD6, A8GB43, A8M9D7, A9A423, A9AAT7, A9CSU5, A9MKA7, B0R4Z6, B1L5U2, B1XW11, B1YAX4, B2U846, B3R5N3, B4EV71, B4RYH7, B5XZG7, B6EHL7, B6YSY7, B7VB85

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CDK5	down-regulates	EPRS1	phosphorylation
ATF4	“up-regulates quantity by expression”	EPRS1	“transcriptional regulation”
EPRS1	“form complex”	“Multiaminoacyl-tRNA synthetase”	binding
RPS6KB1	“up-regulates activity”	EPRS1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 187 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
Cytosolic tRNA aminoacylation	8	28.3×	7e-08
RIP-mediated NFkB activation via ZBP1	5	27.1×	8e-05
tRNA Aminoacylation	8	18.4×	1e-06
TRAF6 mediated NF-kB activation	5	18.4×	4e-04
Selenoamino acid metabolism	11	17.5×	2e-08
Transcriptional and post-translational regulation of MITF-M expression and activity	10	14.4×	3e-07
Activation of NF-kappaB in B cells	8	12.7×	2e-05
Dectin-1 mediated noncanonical NF-kB signaling	7	12.2×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
non-canonical NF-kappaB signal transduction	5	26.0×	1e-03
autophagosome maturation	6	13.0×	2e-03
negative regulation of translation	8	9.7×	1e-03
translation	10	6.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	2
Uncertain significance	274
Likely benign	157
Benign	34

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
1680914	NM_004446.3(EPRS1):c.2905_2908del (p.Glu969fs)	Pathogenic
1703006	NM_004446.3(EPRS1):c.635T>C (p.Ile212Thr)	Pathogenic
1703007	NM_004446.3(EPRS1):c.1459A>G (p.Met487Val)	Pathogenic
2096399	NM_004446.3(EPRS1):c.2716_2717delinsT (p.Asp906fs)	Pathogenic
224871	Single allele	Pathogenic
2751990	NM_004446.3(EPRS1):c.3155G>A (p.Trp1052Ter)	Pathogenic
2761389	NM_004446.3(EPRS1):c.1878T>G (p.Tyr626Ter)	Pathogenic
2818126	NM_004446.3(EPRS1):c.4058G>A (p.Trp1353Ter)	Pathogenic
2865970	NM_004446.3(EPRS1):c.2953C>T (p.Gln985Ter)	Pathogenic
3009472	NM_004446.3(EPRS1):c.4047T>G (p.Tyr1349Ter)	Pathogenic
3089880	NM_004446.3(EPRS1):c.4150C>T (p.Arg1384Ter)	Pathogenic
4774745	NM_004446.3(EPRS1):c.3081G>A (p.Trp1027Ter)	Pathogenic
523134	NM_004446.3(EPRS1):c.1015C>T (p.Arg339Ter)	Pathogenic
523135	NM_004446.3(EPRS1):c.3478C>T (p.Pro1160Ser)	Pathogenic
523136	NM_004446.3(EPRS1):c.3667del (p.Thr1223fs)	Pathogenic
523137	NM_004446.3(EPRS1):c.3377T>C (p.Met1126Thr)	Pathogenic
1979486	NM_004446.3(EPRS1):c.1494+1G>T	Likely pathogenic
3069175	NM_004446.3(EPRS1):c.4444C>A (p.Pro1482Thr)	Likely pathogenic

SpliceAI

4107 predictions. Top by Δscore:

Variant	Effect	Δscore
1:219969119:CAAT:C	acceptor_gain	1.0000
1:219969120:AAT:A	acceptor_gain	1.0000
1:219969122:TC:T	acceptor_loss	1.0000
1:219969123:C:CC	acceptor_gain	1.0000
1:219972030:A:AC	donor_gain	1.0000
1:219972031:A:C	donor_gain	1.0000
1:219972042:A:AC	donor_gain	1.0000
1:219972043:C:CC	donor_gain	1.0000
1:219972064:CTGA:C	donor_loss	1.0000
1:219972065:TGACC:T	donor_loss	1.0000
1:219972066:GA:G	donor_loss	1.0000
1:219972068:C:A	donor_loss	1.0000
1:219972146:CC:C	acceptor_gain	1.0000
1:219972147:CC:C	acceptor_gain	1.0000
1:219973234:CTA:C	donor_loss	1.0000
1:219973265:T:TA	donor_gain	1.0000
1:219973394:ACTCC:A	acceptor_gain	1.0000
1:219973395:CTCC:C	acceptor_gain	1.0000
1:219973395:CTCCC:C	acceptor_gain	1.0000
1:219973396:TCC:T	acceptor_gain	1.0000
1:219973396:TCCCT:T	acceptor_gain	1.0000
1:219973397:CC:C	acceptor_gain	1.0000
1:219973397:CCC:C	acceptor_gain	1.0000
1:219973398:CC:C	acceptor_gain	1.0000
1:219973399:C:CA	acceptor_loss	1.0000
1:219973399:C:CC	acceptor_gain	1.0000
1:219978542:TTAC:T	donor_loss	1.0000
1:219978543:TA:T	donor_loss	1.0000
1:219978544:A:C	donor_loss	1.0000
1:219978545:CCTT:C	donor_loss	1.0000

AlphaMissense

9988 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:219978572:A:G	W1353R	1.000
1:219978572:A:T	W1353R	1.000
1:219980854:A:G	W1153R	1.000
1:219980854:A:T	W1153R	1.000
1:220018466:A:G	W493R	1.000
1:220018466:A:T	W493R	1.000
1:220018478:A:G	W489R	1.000
1:220018478:A:T	W489R	1.000
1:220019017:A:G	L471P	1.000
1:220019989:A:G	W450R	1.000
1:220019989:A:T	W450R	1.000
1:220020024:A:G	L438P	1.000
1:220020032:T:A	K435N	1.000
1:220020032:T:G	K435N	1.000
1:220020033:T:A	K435I	1.000
1:220020034:T:G	K435Q	1.000
1:220024444:C:G	D255H	1.000
1:220025172:T:A	D237V	1.000
1:220025187:A:G	L232P	1.000
1:220025219:G:C	N221K	1.000
1:220025219:G:T	N221K	1.000
1:220025226:A:G	L219P	1.000
1:220025229:G:T	A218D	1.000
1:220025234:T:A	K216N	1.000
1:220025234:T:G	K216N	1.000
1:220025240:A:C	H214Q	1.000
1:220025240:A:T	H214Q	1.000
1:220025244:C:T	G213E	1.000
1:220025245:C:A	G213W	1.000
1:220025245:C:G	G213R	1.000

dbSNP variants (sampled 300 via entrez): RS1000005479 (1:219984604 G>A,C), RS1000050882 (1:220028019 T>C), RS1000165503 (1:220035214 G>T), RS1000172801 (1:220002514 A>G), RS1000210519 (1:219990985 G>A,C), RS1000212921 (1:220046569 G>A,T), RS1000245551 (1:220046792 ACT>A), RS1000362654 (1:220041603 G>A), RS1000404774 (1:219996892 C>G,T), RS1000451942 (1:220047762 G>A), RS1000456760 (1:220015680 A>G,T), RS1000502146 (1:220033132 T>C), RS1000549521 (1:220027779 T>A,G), RS1000555553 (1:220034322 C>T), RS1000602353 (1:220026935 A>G)

Disease associations

OMIM: gene MIM:138295 | disease phenotypes: MIM:617951, MIM:614816

GenCC curated gene-disease

Disease	Classification	Inheritance
leukodystrophy, hypomyelinating, 15	Strong	Autosomal recessive

Mondo (3): leukodystrophy, hypomyelinating, 15 (MONDO:0054782), intellectual disability (MONDO:0001071), Loeys-Dietz syndrome 4 (MONDO:0013897)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000529	Progressive visual loss
HP:0000540	Hypermetropia
HP:0000572	Visual loss
HP:0000639	Nystagmus
HP:0000646	Amblyopia
HP:0000648	Optic atrophy
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001332	Dystonia
HP:0001508	Failure to thrive
HP:0002015	Dysphagia
HP:0002059	Cerebral atrophy
HP:0002079	Hypoplasia of the corpus callosum
HP:0002080	Intention tremor
HP:0002305	Athetosis
HP:0002376	Developmental regression
HP:0002415	Leukodystrophy
HP:0002505	Loss of ambulation
HP:0003429	CNS hypomyelination
HP:0003510	Severe short stature
HP:0003593	Infantile onset
HP:0003621	Juvenile onset

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST004611_2	High light scatter reticulocyte count	1.000000e-17
GCST004612_159	High light scatter reticulocyte percentage of red cells	5.000000e-19
GCST004628_137	Immature fraction of reticulocytes	3.000000e-15
GCST005194_129	Coronary artery disease	6.000000e-09
GCST005956_83	Waist-to-hip ratio adjusted for BMI	1.000000e-19
GCST005957_15	Waist-to-hip ratio adjusted for BMI (age <50)	5.000000e-14
GCST005958_1	Waist-to-hip ratio adjusted for BMI (age >50)	1.000000e-23
GCST005962_1	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	4.000000e-33
GCST007294_107	Body fat distribution (trunk fat ratio)	9.000000e-06
GCST007294_72	Body fat distribution (trunk fat ratio)	1.000000e-18
GCST007294_98	Body fat distribution (trunk fat ratio)	3.000000e-15
GCST007295_21	Body fat distribution (leg fat ratio)	8.000000e-06
GCST007295_45	Body fat distribution (leg fat ratio)	1.000000e-10
GCST007295_80	Body fat distribution (leg fat ratio)	1.000000e-14
GCST007565_151	Morning person	4.000000e-17
GCST008357_20	Mood instability	4.000000e-11
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004341	body fat distribution
EFO:0008328	chronotype measurement
EFO:0008475	mood instability measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3873 (SINGLE PROTEIN)

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

ChEMBL bioactivities

6 potent at pChembl≥5 of 12 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.22	Ki	0.6	nM	CHEMBL1163086
7.49	Kd	32.41	nM	CHEMBL3752910
7.49	ED50	32.41	nM	CHEMBL3752910
7.07	Ki	85	nM	CHEMBL5279127
5.92	Kd	1215	nM	CHEMBL5653589
5.92	ED50	1215	nM	CHEMBL5653589

PubChem BioAssay actives

4 with measured affinity, of 39 total; 4 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
[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl N-[(2S)-pyrrolidine-2-carbonyl]sulfamate	1953975: Binding affinity to human Prolyl-tRNA synthetase	ki	0.0006	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148326: Binding affinity to human EPRS incubated for 45 mins by Kinobead based pull down assay	kd	0.0324	uM
[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl N-[(2R)-pyrrolidine-2-carbonyl]sulfamate	1953975: Binding affinity to human Prolyl-tRNA synthetase	ki	0.0850	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148326: Binding affinity to human EPRS incubated for 45 mins by Kinobead based pull down assay	kd	1.2147	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	5
bisphenol A	affects expression, decreases expression	4
Cadmium Chloride	increases abundance, increases expression, decreases expression	4
sodium arsenite	decreases expression, increases expression	3
Valproic Acid	affects cotreatment, increases expression, decreases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
Tobacco Smoke Pollution	affects expression, increases expression	2
Tunicamycin	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
geldanamycin	increases expression	1
testosterone enanthate	affects expression	1
chloroacetaldehyde	decreases expression	1
sodium arsenate	decreases expression	1
titanium dioxide	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
testosterone undecanoate	affects cotreatment, increases expression	1
arsenite	affects binding, decreases reaction	1
ochratoxin A	decreases expression	1
aflatoxin B2	decreases methylation	1
coumarin	increases phosphorylation	1
perfluorooctane sulfonic acid	increases expression	1
chloropicrin	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
bisphenol S	increases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118708	Binding	Binding affinity to EPRS in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
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