AIMP1

Summary

AIMP1 (aminoacyl tRNA synthetase complex interacting multifunctional protein 1, HGNC:10648) is a protein-coding gene on chromosome 4q24, encoding Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (Q12904). Non-catalytic component of the multisynthase complex.

The protein encoded by this gene is a cytokine that is specifically induced by apoptosis, and it is involved in the control of angiogenesis, inflammation, and wound healing. The release of this cytokine renders the tumor-associated vasculature sensitive to tumor necrosis factor. The precursor protein is identical to the p43 subunit, which is associated with the multi-tRNA synthetase complex, and it modulates aminoacylation activity of tRNA synthetase in normal cells. This protein is also involved in the stimulation of inflammatory responses after proteolytic cleavage in tumor cells. Multiple transcript variants encoding different isoforms have been found for this gene. A pseudogene has been identified on chromosome 20.

Source: NCBI Gene 9255 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypomyelinating leukodystrophy 3 (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 174 total — 15 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 29
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001142416

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10648
Approved symbol	AIMP1
Name	aminoacyl tRNA synthetase complex interacting multifunctional protein 1
Location	4q24
Locus type	gene with protein product
Status	Approved
Aliases	EMAPII, EMAP-2, p43
Ensembl gene	ENSG00000164022
Ensembl biotype	protein_coding
OMIM	603605
Entrez	9255

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 27 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000358008, ENST00000394701, ENST00000442366, ENST00000510207, ENST00000671868, ENST00000671960, ENST00000672003, ENST00000672285, ENST00000672328, ENST00000672337, ENST00000672341, ENST00000672911, ENST00000673018, ENST00000673123, ENST00000673381, ENST00000682186, ENST00000683179, ENST00000684019, ENST00000684504, ENST00000898467, ENST00000925403, ENST00000925404, ENST00000925405, ENST00000925406, ENST00000925407, ENST00000925408, ENST00000925409, ENST00000925410, ENST00000925411, ENST00000925412, ENST00000925413, ENST00000951424

RefSeq mRNA: 3 — MANE Select: NM_001142416 NM_001142415, NM_001142416, NM_004757

CCDS: CCDS3674

Canonical transcript exons

ENST00000672341 — 7 exons

Exon	Start	End
ENSE00001080603	106336869	106337037
ENSE00001080605	106327451	106327564
ENSE00001080606	106331672	106331883
ENSE00001196296	106328076	106328243
ENSE00003633403	106324985	106325118
ENSE00003889738	106347526	106349456
ENSE00003891975	106316550	106316594

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 71.7820 / max 1684.1445, expressed in 1823 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49173	50.7680	1814
49172	17.5179	1775
49176	1.0180	300
49175	0.7966	347
49167	0.4113	213
49166	0.3072	151
49169	0.2741	81
49177	0.2367	75
49174	0.2142	57
49168	0.1143	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.33	gold quality
rectum	UBERON:0001052	94.85	gold quality
tendon	UBERON:0000043	94.77	gold quality
diaphragm	UBERON:0001103	94.68	gold quality
endometrium	UBERON:0001295	94.59	gold quality
monocyte	CL:0000576	94.38	gold quality
mononuclear cell	CL:0000842	94.35	gold quality
leukocyte	CL:0000738	94.15	gold quality
gastrocnemius	UBERON:0001388	94.10	gold quality
islet of Langerhans	UBERON:0000006	94.08	gold quality
muscle of leg	UBERON:0001383	94.07	gold quality
tongue squamous epithelium	UBERON:0006919	93.97	gold quality
cartilage tissue	UBERON:0002418	93.82	gold quality
type B pancreatic cell	CL:0000169	93.80	gold quality
descending thoracic aorta	UBERON:0002345	93.73	gold quality
oviduct epithelium	UBERON:0004804	93.69	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.64	gold quality
popliteal artery	UBERON:0002250	93.61	gold quality
tibial artery	UBERON:0007610	93.61	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.47	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.45	gold quality
aorta	UBERON:0000947	93.43	gold quality
epithelium of nasopharynx	UBERON:0001951	93.34	gold quality
smooth muscle tissue	UBERON:0001135	93.32	gold quality
colonic mucosa	UBERON:0000317	93.31	gold quality
muscle organ	UBERON:0001630	93.30	gold quality
thoracic aorta	UBERON:0001515	93.23	gold quality
fallopian tube	UBERON:0003889	93.21	gold quality
cervix epithelium	UBERON:0004801	93.20	gold quality
ascending aorta	UBERON:0001496	93.19	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6386	no	412.73
E-MTAB-10290	no	186.76
E-CURD-112	no	3.37
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

77 targeting AIMP1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-4645-3P	99.76	69.33	993

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• These results suggest the potential interaction of p43/EMAP II with alpha-ATP synthase and its role in the proliferation of endothelial cells. (PMID:11741979)
• temporal variation in EMAP II expression in the human endometrium across the menstrual cycle and localize expression to glandular epithelial, endothelial, and stromal cells. Moreover, EMAP II expression is negatively regulated by PGE(2). (PMID:12161535)
• p43-induced TNF production was mediated by the activation of MAPK family members, ERK and p38 MAPK, and by IkappaB degradation leading to the activation of NFkappaB. (PMID:12543078)
• Expression of endothelial monocyte activating polypeptide II is increased after spinal cord injury (SCI), suggesting a role for EMAP II in the pathophysiology of secondary injury following SCI. (PMID:14588117)
• Membrane-bound and soluble EMAP-II appear to play multiple roles in the tumor microenvironment, one of which is to assist in immune evasion. (PMID:14688335)
• EMAP-II causes a dose-dependent inhibition of proliferation and apoptosis in Jurkat T cells and mitogen-activated peripheral blood mononuclear cells, suggesting that EMAP-II constitutes a component of a novel, immunosuppressive pathway in solid tumors (PMID:14982944)
• DOC1 might play a role in mediating some of the effects of EMAP-II on endothelial cells (PMID:15935955)
• Expression of the cleaved EMAP-II form in tumour-biopsies correlates with a good response of melanoma patients to TNF-based ILP. (PMID:16615114)
• EMAP II is cleaved by MMP-9, elastase, and cathepsin L. (PMID:16674941)
• Three-dimensional structure is projected from amino acid sequence. (PMID:17018011)
• EMAP-II facilitates apoptotic signaling of TNF-R1 via mobilization of TRADD. (PMID:17051333)
• suggest that the cleavage of p43 and its cellular delocalization (PMID:17303557)
• Arginyl t-RNA synthetase over-expression associates with a reduced AIMP1 secretion. Multicatalytic protease is involved in the generation of the mature cytokine, EMAP II. (PMID:17443684)
• serum EMAP-II levels are significantly higher in patients with NSCLC than in healthy subjects and suggest it is of potential prognostic value (PMID:18621627)
• Results suggest novel roles for EMAP II in modulating the migration of dendritic cells and suggest that these effects may modify Meth A tumor/host interactions. (PMID:18951814)
• Inhibition of VEGF signaling is one possible antiangiogenic mechanism of EMAP II, which may explain its in vivo antitumor activity and delineate therapeutic strategies to enhance anti-VEGF therapy to inhibit tumor growth. (PMID:19002109)
• one of the major anti-angiogenic functions of EMAP-II is exerted through its inhibition of the HIF-1alpha activities (PMID:19362550)
• EMAP-II plays an important role in endothelial cell dysfunction related to graft-versus-host disease after allogeneic stem cell transplantation. (PMID:19565673)
• AIMP1 may exert its antitumor activity by inducing tumor-suppressing cytokines. After a single intravenous injection, AMP1 exhibited a low clearance showing a one-compartmental disposition. (PMID:19573982)
• this is the first report showing evidence for the chemoattractant properties of EMAPII on leech and human microglial cells (PMID:19917687)
• p43 is cleaved during apoptosis by calpains and released as a truncated protein that is harmless for the structure of the atherosclerotic plaque. (PMID:20413730)
• autoantibodies of aminoacyl-tRNA synthetase can be used in the diagnosis of type I diabetes (PMID:20429837)
• LPS induces the dissociation of gp96 from AIMP1 by phosphorylation through TLR4/MyD88-mediated JNK activation, resulting in translocation of gp96 on the cell surface. (PMID:20510162)
• The known pathological functions together with abundant cellular accumulation in cerebral ischemia lesions suggest that EMAPII might contribute to pathophysiological consequences of cerebral ischemia. (PMID:21047177)
• Through genome-wide homozygosity mapping and mutation analysis, we demonstrated in all affected individuals a homozygous frameshift mutation that fully abrogates the main active domain of AIMP1 (PMID:21092922)
• we propose that AIMP1 effect on EC adhesion is mediated by the assembly of a cytoskeletal protein complex on the cytosolic face of the cell membrane (PMID:21416500)
• EMAPII is elevated in the BALF of active smokers and patients with COPD. Expression was increased in COPD lungs and emphysema. (PMID:21576822)
• Decreased expression of AIMP1 in gastric and colorectal cancer tissues suggests that down-regulation of this protein may be related to inactivation of the tumor suppressor functions of AIMP proteins and might play a role in the development of GC and CRC. (PMID:21789020)
• EMAP II has specific intracellular effects, and that this intracellular function appears to antagonize its extracellular anti-angiogenic effects during fetal development and pulmonary disease progression. (PMID:22412987)
• Downregulation of CD23 attenuated AIMP1-induced TNF-alpha secretion and AIMP1 binding. (PMID:22767513)
• EMAP-II transcripts are upregulated in tumour cells in hypoxic conditions. (PMID:23082492)
• AIMP1 peptide promotes the proliferation of BMMSCs by activating the beta-catenin/TCF complex via FGFR2-mediated activation of Akt, which leads to an increase in mesenchymal stem cells in peripheral blood. (PMID:23672191)
• Kisspeptin effect on endothelial monocyte activating polypeptide II (EMAP-II)-associated lymphocyte cell death and metastases in colorectal cancer patients (PMID:24395571)
• vascular contribution to lung development and the implications that vascular mediators such as EMAP II have in distal lung formation during the vulnerable stage of alveolar genesis. (PMID:24619875)
• Data indicate that HCV E2 glycoprotein interacts with cellular AIMP1/p43 protein and promotes cell surface expression of membrane glycoproteins gp96 and transforming growth factor beta TGF-beta signaling. (PMID:24816397)
• AIMP1 appears to function as a novel inhibitor of PPARgamma that regulates adipocyte differentiation by preventing the transcriptional activation of PPARgamma. (PMID:25146391)
• interactions between the N-terminal domains of ArgRS and AIMP1 are important for the catalytic and noncatalytic activities of ArgRS and for the assembly of the higher-order MSC protein complex with ArgRS-GlnRS-AIMP1 (PMID:25288775)
• Data indicate that the N terminus of Pro-EMAP II binds to its C terminus, arginyl-tRNA synthetase, and the neurofilament light subunit. (PMID:25724651)
• EMAP2 is a multifunctional polypeptide with proinflammatory and antiangiogenic activity. (Review) (PMID:26040042)
• findings suggest EMAP II is elevated in type 1 diabetic patients, particularly those with micro-vascular complications; EMAP II levels are related to inflammation, glycemic control, albuminuria level of patients and the risk of micro-vascular complications (PMID:26142824)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	aimp1b	ENSDARG00000036894
danio_rerio	aimp1a	ENSDARG00000060036
mus_musculus	Aimp1	ENSMUSG00000028029
rattus_norvegicus	Aimp1	ENSRNOG00000011384
drosophila_melanogaster	AIMP1	FBGN0033351

Protein

Protein identifiers

Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 — Q12904 (reviewed: Q12904)

Alternative names: Multisynthase complex auxiliary component p43

All UniProt accessions (6): A0A5F9ZHC5, A0A804HJ47, A0A8C8KIA0, A0A8C8MUD1, D6R937, Q12904

UniProt curated annotations — full annotation on UniProt →

Function. Non-catalytic component of the multisynthase complex. Stimulates the catalytic activity of cytoplasmic arginyl-tRNA synthase. Binds tRNA. Possesses inflammatory cytokine activity. Negatively regulates TGF-beta signaling through stabilization of SMURF2 by binding to SMURF2 and inhibiting its SMAD7-mediated degradation. Involved in glucose homeostasis through induction of glucagon secretion at low glucose levels. Promotes dermal fibroblast proliferation and wound repair. Regulates KDELR1-mediated retention of HSP90B1/gp96 in the endoplasmic reticulum. Plays a role in angiogenesis by inducing endothelial cell migration at low concentrations and endothelial cell apoptosis at high concentrations. Induces maturation of dendritic cells and monocyte cell adhesion. Modulates endothelial cell responses by degrading HIF-1A through interaction with PSMA7.

Subunit / interactions. Homodimer. Part of the multisynthetase complex (MSC), a multisubunit complex that groups 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. Interacts (via N-terminus) with RARS1 (via N-terminus). Part of a complex composed of RARS1, QARS1 and AIMP1. Interacts (via C-terminus) with SMURF2. Interacts (via N-terminus) with HSP90B1/gp96 (via C-terminus). Interacts with PSMA7. Interacts with TARS3.

Subcellular location. Nucleus. Cytoplasm. Cytosol. Secreted. Endoplasmic reticulum. Golgi apparatus.

Post-translational modifications. Cleaved by caspase-7 in response to apoptosis to produce EMAP-II.

Disease relevance. Leukodystrophy, hypomyelinating, 3 (HLD3) [MIM:260600] A severe autosomal recessive hypomyelinating leukodystrophy characterized by early infantile onset of global developmental delay, lack of development, lack of speech acquisition, and peripheral spasticity associated with decreased myelination in the central nervous system. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q12904-1	1	yes
Q12904-2	2

RefSeq proteins (3): NP_001135887, NP_001135888, NP_004748 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002547	tRNA-bd_dom	Domain
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR051270

Pfam: PF01588

UniProt features (41 total): strand 13, helix 5, region of interest 5, modified residue 4, sequence variant 3, turn 3, chain 2, initiator methionine 1, cross-link 1, splice variant 1, sequence conflict 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
1FL0	X-RAY DIFFRACTION	1.5
1EUJ	X-RAY DIFFRACTION	1.8
1E7Z	X-RAY DIFFRACTION	2.05
8J9S	X-RAY DIFFRACTION	3.01
4R3Z	X-RAY DIFFRACTION	4.03
8ONG	SOLUTION NMR, SOLUTION SCATTERING

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12904-F1	81.68	0.67

Functional residue map

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

Post-translational modifications (5): 2, 140, 269, 137, 1

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-2408522	Selenoamino acid metabolism
R-HSA-379716	Cytosolic tRNA aminoacylation
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-72766	Translation
R-HSA-9730414	MITF-M-regulated melanocyte development

MSigDB gene sets: 267 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_AMINO_ACID_ACTIVATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, chr4q24, GOBP_INFLAMMATORY_RESPONSE, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_TRNA_METABOLIC_PROCESS, MORF_ATRX, GOBP_REGULATION_OF_HORMONE_LEVELS, GOCC_CELL_SURFACE, GOBP_HORMONE_TRANSPORT, GOMF_GTPASE_BINDING, GGGTGGRR_PAX4_03, GOBP_CELL_CELL_SIGNALING

GO Biological Process (11): angiogenesis (GO:0001525), negative regulation of endothelial cell proliferation (GO:0001937), translation (GO:0006412), apoptotic process (GO:0006915), inflammatory response (GO:0006954), cell-cell signaling (GO:0007267), leukocyte migration (GO:0050900), defense response to virus (GO:0051607), positive regulation of glucagon secretion (GO:0070094), signal transduction (GO:0007165), blood vessel morphogenesis (GO:0048514)

GO Molecular Function (6): tRNA binding (GO:0000049), cytokine activity (GO:0005125), protein homodimerization activity (GO:0042803), GTPase binding (GO:0051020), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (10): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), cell surface (GO:0009986), membrane (GO:0016020), aminoacyl-tRNA synthetase multienzyme complex (GO:0017101), extracellular region (GO:0005576), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-7 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular membrane-bounded organelle	3
cytoplasm	3
defense response	2
cell communication	2
signaling	2
endomembrane system	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	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
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
immune system process	1
cell migration	1
response to virus	1
glucagon secretion	1
regulation of glucagon secretion	1
positive regulation of peptide hormone secretion	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
blood vessel development	1
tube morphogenesis	1
RNA binding	1
receptor ligand activity	1
identical protein binding	1
protein dimerization activity	1
enzyme binding	1
nucleic acid binding	1
binding	1

Protein interactions and networks

STRING

3412 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AIMP1	AIMP2	Q13155	979
AIMP1	EEF1E1	O43324	972
AIMP1	QARS1	P47897	895
AIMP1	AARS1	P49588	880
AIMP1	RARS2	Q5T160	865
AIMP1	RARS1	P54136	863
AIMP1	HYCC1	Q9BYI3	844
AIMP1	EPRS1	P07814	813
AIMP1	WARS2	Q9UGM6	800
AIMP1	WARS1	P23381	765
AIMP1	CPS1	P31327	754
AIMP1	MARS1	P56192	734
AIMP1	MARS2	Q96GW9	726
AIMP1	KARS1	Q15046	725
AIMP1	GJC2	Q5T442	725

IntAct

143 interactions, top by confidence:

A	B	Type	Score
AIMP2	AIMP1	psi-mi:“MI:0915”(physical association)	0.790
AIMP1	AIMP2	psi-mi:“MI:0915”(physical association)	0.790
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
AIMP1	RARS1	psi-mi:“MI:0914”(association)	0.640
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
TSNAX	AIMP1	psi-mi:“MI:0915”(physical association)	0.560
AIMP1	TSNAX	psi-mi:“MI:0915”(physical association)	0.560
AIMP1	gag	psi-mi:“MI:0915”(physical association)	0.560
NEURL4	APBB1	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
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
gag	SDCBP	psi-mi:“MI:0914”(association)	0.460
TGOLN2	PGRMC1	psi-mi:“MI:0914”(association)	0.420
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (362): AIMP1 (Two-hybrid), AIMP1 (Two-hybrid), AIMP1 (Affinity Capture-MS), AIMP1 (Affinity Capture-MS), AIMP1 (Co-fractionation), AIMP1 (Co-fractionation), AIMP1 (Co-fractionation), AIMP1 (Co-fractionation), AIMP1 (Co-fractionation), AIMP1 (Co-fractionation), AIMP1 (Co-fractionation), AIMP1 (Co-fractionation), AIMP1 (Co-fractionation), AIMP1 (Co-fractionation), AIMP1 (Co-fractionation)

ESM2 similar proteins: A0A0R4IXF6, A0M8S4, A0M8T5, A1A5Q0, A1X157, B9EJA2, F6QZ15, O54873, O60308, O75764, P23881, P31230, P49916, P97386, Q00PJ1, Q02225, Q07DV1, Q07DW4, Q07DX4, Q07DY4, Q07E15, Q07E28, Q07E41, Q09YG9, Q09YI1, Q09YJ3, Q09YK4, Q09YM8, Q108T9, Q12904, Q1LUC3, Q2IBA2, Q2IBB2, Q2IBD4, Q2IBE6, Q2IBF7, Q2IBF8, Q2KI09, Q2QL82, Q2QLA2

Diamond homologs: A0K9L0, A0L8S1, A0M5Z9, A1TZ66, A1V5W0, A2SAF7, A2SRE2, A3MLM5, A3N6Y1, A3NSL6, A3QD92, A4FZL1, A4JGW6, A5FLM7, A6GVQ2, A6LFP0, A6SX05, A6URW2, A6UUN1, A6VIW5, A9AHJ8, A9FBU8, B1J1D1, B1JWS3, B1XWM2, B1YUT2, B2RHF5, B3R678, B4E8E0, B5ENA8, B6YUN0, B7J7Y5, O28819, O33925, O54873, O58721, P23395, P31230, P42589, P46672

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MAPK8	down-regulates	AIMP1	phosphorylation
AIMP1	up-regulates	SMURF2	binding
AIMP1	“up-regulates activity”	SMURF2	binding
AIMP1	“form complex”	“Multiaminoacyl-tRNA synthetase”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 131 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	6	28.6×	4e-05
tRNA Aminoacylation	6	18.6×	1e-04
Selenoamino acid metabolism	7	15.0×	1e-04
Transcriptional and post-translational regulation of MITF-M expression and activity	7	13.6×	1e-04
MITF-M-regulated melanocyte development	8	9.9×	2e-04
CLEC7A (Dectin-1) signaling	6	9.3×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	4
Uncertain significance	87
Likely benign	27
Benign	16

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1172642	NM_001142416.2(AIMP1):c.82C>T (p.Gln28Ter)	Pathogenic
1365093	NM_001142416.2(AIMP1):c.692_695dup (p.Pro233fs)	Pathogenic
2017299	NM_001142416.2(AIMP1):c.89_92del (p.Ser30fs)	Pathogenic
2088801	NM_001142416.2(AIMP1):c.78del (p.Lys26fs)	Pathogenic
2159413	NM_001142416.2(AIMP1):c.191_192del (p.Gln64fs)	Pathogenic
243083	NM_001142416.2(AIMP1):c.334C>T (p.Gln112Ter)	Pathogenic
2576924	NM_001142416.2(AIMP1):c.145C>T (p.Arg49Ter)	Pathogenic
2750527	NM_001142416.2(AIMP1):c.411del (p.Lys137fs)	Pathogenic
2788051	NM_001142416.2(AIMP1):c.670C>T (p.Gln224Ter)	Pathogenic
30372	NM_001142416.2(AIMP1):c.292_293del (p.Gln98fs)	Pathogenic
3246736	NC_000004.11:g.(?107268663)(107268849_?)del	Pathogenic
3384795	NM_001142416.2(AIMP1):c.895G>A (p.Gly299Arg)	Pathogenic
3776127	NM_001142416.2(AIMP1):c.695C>A (p.Ser232Ter)	Pathogenic
58034	GRCh38/hg38 4q24-25(chr4:105778347-110206873)x3	Pathogenic
590774	NM_001142416.2(AIMP1):c.162del (p.Lys54fs)	Pathogenic
2579589	NM_001142416.2(AIMP1):c.223+1G>A	Likely pathogenic
2630166	NM_001142416.2(AIMP1):c.706del (p.Ile236fs)	Likely pathogenic
3391194	NM_001142416.2(AIMP1):c.347del (p.Gly116fs)	Likely pathogenic
4813746	NM_001142416.2(AIMP1):c.441_442insTT (p.Lys148fs)	Likely pathogenic

SpliceAI

1681 predictions. Top by Δscore:

Variant	Effect	Δscore
4:106316547:CATG:C	donor_gain	1.0000
4:106316553:T:TA	donor_gain	1.0000
4:106324981:A:AG	acceptor_gain	1.0000
4:106324981:ATAG:A	acceptor_gain	1.0000
4:106324981:ATAGG:A	acceptor_loss	1.0000
4:106324982:T:G	acceptor_gain	1.0000
4:106324982:TAGGA:T	acceptor_loss	1.0000
4:106324983:A:AG	acceptor_gain	1.0000
4:106324983:AG:A	acceptor_gain	1.0000
4:106324983:AGGAT:A	acceptor_loss	1.0000
4:106324984:G:GA	acceptor_gain	1.0000
4:106324984:GG:G	acceptor_gain	1.0000
4:106324984:GGA:G	acceptor_gain	1.0000
4:106324984:GGAT:G	acceptor_gain	1.0000
4:106324984:GGATT:G	acceptor_gain	1.0000
4:106325091:C:T	donor_gain	1.0000
4:106325115:GCAA:G	donor_gain	1.0000
4:106325116:CAA:C	donor_gain	1.0000
4:106325117:AA:A	donor_gain	1.0000
4:106325117:AAG:A	donor_loss	1.0000
4:106325118:AG:A	donor_loss	1.0000
4:106325119:G:GG	donor_gain	1.0000
4:106325120:T:G	donor_loss	1.0000
4:106327449:A:AG	acceptor_gain	1.0000
4:106327450:G:GT	acceptor_gain	1.0000
4:106327450:GT:G	acceptor_gain	1.0000
4:106327450:GTT:G	acceptor_gain	1.0000
4:106327562:G:GT	donor_gain	1.0000
4:106328074:A:AG	acceptor_gain	1.0000
4:106328075:G:GA	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000011617 (4:106334551 C>T), RS1000196221 (4:106322169 C>G), RS1000281122 (4:106343109 A>T), RS1000450000 (4:106329943 T>A), RS1000466443 (4:106334864 A>G), RS1000613557 (4:106329784 T>C), RS1000728587 (4:106323501 T>C), RS1000744266 (4:106317442 G>A), RS1000764625 (4:106347897 G>A), RS1000768889 (4:106323267 T>C), RS1000862103 (4:106342770 T>A,C), RS1000900230 (4:106343097 T>A,C), RS1000959121 (4:106336308 C>G), RS1001078443 (4:106317778 T>C), RS1001124551 (4:106327312 A>G)

Disease associations

OMIM: gene MIM:603605 | disease phenotypes: MIM:260600

GenCC curated gene-disease

Disease	Classification	Inheritance
hypomyelinating leukodystrophy 3	Strong	Autosomal recessive
autosomal recessive non-syndromic intellectual disability	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
hypomyelinating leukodystrophy 3	Definitive	AR

Mondo (2): hypomyelinating leukodystrophy 3 (MONDO:0009843), autosomal recessive non-syndromic intellectual disability (MONDO:0019502)

Orphanet (2): Pelizaeus-Merzbacher-like disease (Orphanet:280270), Pelizaeus-Merzbacher-like disease due to AIMP1 mutation (Orphanet:280293)

HPO phenotypes

29 total (29 of 29 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000505	Visual impairment
HP:0000577	Exotropia
HP:0000639	Nystagmus
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001344	Absent speech
HP:0001508	Failure to thrive
HP:0001522	Death in infancy
HP:0001622	Premature birth
HP:0002283	Global brain atrophy
HP:0002313	Spastic paraparesis
HP:0002353	EEG abnormality
HP:0002415	Leukodystrophy
HP:0002587	Projectile vomiting
HP:0002751	Kyphoscoliosis
HP:0003269	Sudanophilic leukodystrophy
HP:0003593	Infantile onset
HP:0003676	Progressive
HP:0006918	Diffuse cerebral sclerosis
HP:0007210	Lower limb amyotrophy
HP:0007256	Abnormal pyramidal sign
HP:0007371	Corpus callosum atrophy
HP:0008936	Axial hypotonia
HP:0030211	Slow pupillary light response
HP:0034353	Appendicular spasticity
HP:0034392	Joint contracture

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536319	Pelizaeus-Merzbacher-like disease, autosomal recessive, 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295810 (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
7.24	Kd	57.38	nM	CHEMBL5653589
7.24	ED50	57.38	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 5 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147825: Binding affinity to human AIMP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0574	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
bisphenol A	affects expression, decreases expression, increases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
dicrotophos	decreases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
nickel chloride	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ochratoxin A	increases expression	1
epigallocatechin gallate	decreases expression	1
CGP 52608	increases reaction, affects binding	1
GW 7604	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
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects expression	1
jinfukang	decreases expression	1
Vorinostat	decreases expression	1
Acetylcysteine	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Cannabidiol	decreases expression, decreases reaction	1
Cannabinoids	decreases expression, decreases reaction, increases abundance	1
Carbamazepine	affects expression	1
Clozapine	increases expression	1
Doxorubicin	decreases 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
CHEMBL4119010	Binding	Binding affinity to AIMP1 in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1Q1	HAP1 AIMP1 (-) 1	Cancer cell line	Male
CVCL_E1Q2	HAP1 AIMP1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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