AIMP1

Chr 4

aminoacyl tRNA synthetase complex interacting multifunctional protein 1

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

NCBI Gene: 9255 ENSG00000164022 UniProt: Q12904

The protein functions as the p43 subunit of the multi-tRNA synthetase complex, modulating aminoacylation activity of tRNA synthetase, and also acts as a cytokine involved in controlling angiogenesis, inflammation, and wound healing when released from cells. Mutations cause autosomal recessive hypomyelinating leukodystrophy type 3. The pathogenic mechanism likely involves disruption of protein synthesis through impaired tRNA aminoacylation.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 1.22

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

22 unique Pathogenic / Likely Pathogenic· 81 VUS of 168 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.21Z-score

OE missense 1.04 (0.93–1.18)

182 obs / 174.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.75 (0.48–1.22)

0≤0.351.4

Missense OE?1.04 (0.93–1.18)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 12 / 16.0Missense obs/exp: 182 / 174.3Syn Z: 0.50

ClinVar Variant Classifications

168 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15

Likely Pathogenic7

VUS81

Likely Benign29

Benign16

Conflicting3

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	13	1	1	0	15
Likely Pathogenic	7	0	0	0	7
VUS	1	77	3	0	81
Likely Benign	0	5	10	14	29
Benign	0	2	12	2	16
Conflicting	—				3
Total	21	85	26	16	151

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap AIMP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →