AIMP2

Chr 7AR

aminoacyl tRNA synthetase complex interacting multifunctional protein 2

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

NCBI Gene: 7965 ENSG00000106305 UniProt: Q13155 OMIM: 600859

The encoded protein is a non-enzymatic factor required for assembly and stability of the aminoacyl-tRNA synthetase complex, which is essential for protein synthesis. Mutations cause hypomyelinating leukodystrophy 17, inherited in an autosomal recessive pattern. This gene shows low constraint to loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.971 OMIM phenotype

Clinical Summary— AIMP2

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Gene-Disease Validity (ClinGen)

leukodystrophy, hypomyelinating, 17 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.97LOEUF

pLI 0.008

Z-score 1.65

OE 0.46 (0.24–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.85Z-score

OE missense 1.17 (1.05–1.31)

227 obs / 193.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.46 (0.24–0.97)

0≤0.351.4

Missense OE?1.17 (1.05–1.31)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 5 / 10.9Missense obs/exp: 227 / 193.7Syn Z: -1.57

This gene — mechanism propensity

0.6259th %ile

GOF

0.4677th %ile

LOF

0.3261th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.