AIMP1

Chr 4AR

aminoacyl tRNA synthetase complex interacting multifunctional protein 1

Also known as: EMAP2, EMAPII, HLD3, SCYE1, p43

NCBI Gene: 9255ENSG00000164022UniProt: Q12904

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. [provided by RefSeq, Dec 2008]

Primary Disease Associations & Inheritance

Leukodystrophy, hypomyelinating, 3MIM #260600
AR
169
ClinVar variants
33
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— AIMP1
🧬
Gene-Disease Validity (ClinGen)
hypomyelinating leukodystrophy 3 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 88 VUS of 169 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.22LOEUF
pLI 0.000
Z-score 0.92
OE 0.75 (0.48–1.22)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.21Z-score
OE missense 1.04 (0.93–1.18)
182 obs / 174.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.75 (0.48–1.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (0.93–1.18)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 12 / 16.0Missense obs/exp: 182 / 174.3Syn Z: 0.50

ClinVar Variant Classifications

169 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic7
VUS88
Likely Benign29
Benign16
Conflicting3
26
Pathogenic
7
Likely Pathogenic
88
VUS
29
Likely Benign
16
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
1
18
0
26
Likely Pathogenic
5
0
2
0
7
VUS
1
74
13
0
88
Likely Benign
0
5
10
14
29
Benign
0
2
12
2
16
Conflicting
—3
Total13825516169

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

AIMP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

AIMP1-related leukodystrophy, hypomyelinating

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Leukodystrophy, hypomyelinating, 3

MIM #260600

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The Genetic Landscape of Epilepsy of Infancy with Migrating Focal Seizures.
Burgess R et al.·Ann Neurol
2019
A Novel Homozygous Splice Site Variant in AIMP1 Gene Causing Hypomyelinating Leukodystrophy: Case Report and Review of the Literature.
Quental R et al.·Neuropediatrics
2023Review
Genetic etiology of ventriculomegaly in 73 fetuses identified by High-Throughput sequencing.
Chenyue Z et al.·Sci Rep
2025
The Role of the AIMP1 Pathway in Diabetic Retinopathy: AIMP1-Targeted Intervention Study in Diabetic Retinopathy.
Zou C et al.·Ophthalmic Res
2020
Clinical powers of Aminoacyl tRNA Synthetase Complex Interacting Multifunctional Protein 1 (AIMP1) for head-neck squamous cell carcinoma.
Li Y et al.·Cancer Biomark
2022Functional
Hereditary Spastic Paraplegia Linked to Abnormal Splicing From an AIMP1 Missense Variant.
Morais S et al.·Clin Genet
2025
Missense variants in AIMP1 gene are implicated in autosomal recessive intellectual disability without neurodegeneration.
Iqbal Z et al.·Eur J Hum Genet
2016
Sulforaphane targets STAT3-CKMT2-AS1 to suppress gastric cancer via PSMB8 downregulation and AIMP1 stabilization.
Liu PT et al.·Phytomedicine
2025
Peripheral nerves are involved in hypomyelinating leukodystrophy-3 caused by a homozygous AIMP1 variant.
Hori I et al.·Brain Dev
2021Case report
Pathogenic variants in AIMP1 cause pontocerebellar hypoplasia.
Accogli A et al.·Neurogenetics
2019Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools