AIMP2

Chr 7AR

aminoacyl tRNA synthetase complex interacting multifunctional protein 2

Also known as: HLD17, JTV-1, JTV1, P38

NCBI Gene: 7965ENSG00000106305UniProt: Q13155

The protein encoded by this gene is part of the aminoacyl-tRNA synthetase complex, which contains nine different aminoacyl-tRNA synthetases and three non-enzymatic factors. The encoded protein is one of the non-enzymatic factors and is required for assembly and stability of the complex. [provided by RefSeq, May 2016]

Primary Disease Associations & Inheritance

Leukodystrophy, hypomyelinating, 17MIM #618006
AR
263
ClinVar variants
61
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— AIMP2
🧬
Gene-Disease Validity (ClinGen)
leukodystrophy, hypomyelinating, 17 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
61 Pathogenic / Likely Pathogenic· 129 VUS of 263 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.
0.97LOEUF
pLI 0.008
Z-score 1.65
OE 0.46 (0.24–0.97)
Tolerant

Typical tolerance to LoF variation

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.
-0.85Z-score
OE missense 1.17 (1.05–1.31)
227 obs / 193.7 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.0.46 (0.24–0.97)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.17 (1.05–1.31)
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.1.21
0≤1.21.6
LoF obs/exp: 5 / 10.9Missense obs/exp: 227 / 193.7Syn Z: -1.57

ClinVar Variant Classifications

263 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic7
VUS129
Likely Benign55
Benign17
Conflicting1
54
Pathogenic
7
Likely Pathogenic
129
VUS
55
Likely Benign
17
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
52
0
54
Likely Pathogenic
2
1
4
0
7
VUS
2
91
35
1
129
Likely Benign
1
3
10
41
55
Benign
0
5
7
5
17
Conflicting
—1
Total710010847263

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

View in ClinVar →

Protein Context — Lollipop Plot

AIMP2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Leukodystrophy, hypomyelinating, 17

MIM #618006

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification and structure of AIMP2-DX2 for therapeutic perspectives.
Kim HJ et al.·BMB Rep
2024Review
Identification of sixteen novel candidate genes for late onset Parkinson's disease.
Gialluisi A et al.·Mol Neurodegener
2021
AIMP2-DX2 provides therapeutic interface to control KRAS-driven tumorigenesis.
Kim DG et al.·Nat Commun
2022
Bi-directional regulation of AIMP2 and its splice variant on PARP-1-dependent neuronal cell death; Therapeutic implication for Parkinson's disease.
Lee MH et al.·Acta Neuropathol Commun
2024
Structural insight into the interaction between p53 TAD1 and AIMP2-DX2 by NMR.
Cho HY et al.·Biochem Biophys Res Commun
2020
Discovery of benzodioxane analogues as lead candidates of AIMP2-DX2 inhibitors.
Lee B et al.·Bioorg Med Chem Lett
2022
An Isoform of the Oncogenic Splice Variant AIMP2-DX2 Detected by a Novel Monoclonal Antibody.
Kim DG et al.·Biomolecules
2020
Amyloid-like oligomerization of AIMP2 contributes to α-synuclein interaction and Lewy-like inclusion.
Ham S et al.·Sci Transl Med
2020
Purification and biophysical characterization of the AIMP2-DX2 protein.
Jha R et al.·Protein Expr Purif
2017
Synthesis and Structure-Activity Relationships of Arylsulfonamides as AIMP2-DX2 Inhibitors for the Development of a Novel Anticancer Therapy.
Sivaraman A et al.·J Med Chem
2020
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