On this page
AIMP1
aminoacyl tRNA synthetase complex interacting multifunctional protein 1
AIMP1 is located on the long (q) arm of chromosome 4, at band 4q24. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 4 in the library →Available at Jeen Health
Clinical tests that include this
Overview
AIMP1 encodes aminoacyl tRNA synthetase complex interacting multifunctional protein 1, a scaffold protein that binds to and stabilises the multi-aminoacyl-tRNA synthetase complex. This complex ensures the accurate charging of transfer RNA molecules with their corresponding amino acids during protein synthesis. Beyond supporting translation, AIMP1 has independent functions in cell signalling, participating in processes ranging from endothelial cell migration to fibroblast proliferation. Pathogenic variants in AIMP1 have been linked to neurological presentations including childhood-onset spastic paraplegia, epilepsy, and intellectual disability, reflecting the protein's importance in nervous system development and function.
What the gene does
The AIMP1 protein serves as a non-catalytic component of the aminoacyl-tRNA synthetase complex, where it acts primarily as a scaffold to organise and stabilise the catalytic enzymes responsible for attaching amino acids to their cognate tRNA molecules. This process is fundamental to ensuring the fidelity of protein synthesis in all cells. Beyond its structural role in translation, AIMP1 functions independently in several signalling pathways. The protein regulates fibroblast proliferation through mechanisms that involve its N-terminal region, and it influences endothelial cell behaviour by coordinating migration and programmed cell death in response to cellular signals. AIMP1 also interacts with heat shock proteins, including HSP90B1, suggesting involvement in the cellular stress response and protein quality control. These diverse functions indicate that AIMP1 participates in both housekeeping cellular activities and specialised regulatory pathways that are particularly important in tissues with high metabolic demands.
Video: Genetics 101
Chromosome location
AIMP1 is located on the long arm of chromosome 4 at position 4q24. This chromosomal region contains numerous genes, and the precise genomic context may influence AIMP1 expression patterns across different tissues. The gene encodes a protein of 312 amino acids, with the coding sequence distributed across multiple exons that are transcribed and spliced to produce the mature messenger RNA template for translation.
Protein structure
The AIMP1 protein spans 312 amino acids and contains several functionally distinct regions that mediate its diverse cellular roles. The N-terminal region from amino acids 6 to 46 is required for fibroblast proliferation, establishing an early functional domain in the protein sequence. A central region encompassing amino acids 54 to 194 mediates interaction with HSP90B1, the heat shock protein involved in cellular stress responses and protein folding. Within this broader region, a shorter segment from amino acids 101 to 114 is specifically required for endothelial cell death, whilst the adjacent region from amino acids 114 to 192 is necessary for endothelial cell migration, highlighting how overlapping domains coordinate related cellular processes. The protein contains a disordered region spanning amino acids 107 to 147, which may provide structural flexibility for dynamic protein-protein interactions. Towards the C-terminus, a tRNA-binding domain extends from amino acids 151 to 252, enabling AIMP1 to interact directly with transfer RNA molecules and participate in the aminoacyl-tRNA synthetase complex assembly and function.
Key variants
Pathogenic variants in AIMP1 disrupt either the protein's structural role in the aminoacyl-tRNA synthetase complex or its independent signalling functions, leading to impaired protein synthesis or dysregulated cellular processes. The neurological manifestations associated with AIMP1 variants suggest that nervous system tissues are particularly vulnerable to these disruptions, possibly due to their high demand for accurate protein production and sensitivity to cellular stress.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.115C>T | p.Gln39Ter | Pathogenic/Likely pathogenic | ★★☆☆ | AIMP1-related disorder |
c.162del | p.Lys54fs | Pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 3 |
c.191_192del | p.Gln64fs | Pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 3 |
c.267_282del | p.Asn89fs | Pathogenic/Likely pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 3 |
c.334C>T | p.Gln112Ter | Pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 3 |
c.362_366del | p.Lys121fs | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.692_695dup | p.Pro233fs | Pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 3 |
g.(?_107268663)_(107268849_?)del | - | Pathogenic | ★☆☆☆ | not provided |
c.250_252delinsGG | p.Thr84fs | Pathogenic | ★☆☆☆ | Leukodystrophy, hypomyelinating, 3 |
c.670C>T | p.Gln224Ter | Pathogenic | ★☆☆☆ | not provided |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in AIMP1 have been associated with a spectrum of neurological conditions characterised by motor impairment, seizures, and developmental delay. These presentations include childhood-onset hereditary spastic paraplegia, which involves progressive stiffness and weakness of the lower limbs, and early-onset epilepsy syndromes. Affected individuals may also present with intellectual disability and white matter abnormalities visible on brain imaging, reflecting widespread effects on nervous system structure and function.
No disease links recorded for this gene in our reference set.
UK clinical status
Within the NHS Genomic Medicine Service, AIMP1 appears on several clinical gene panels with green classification, indicating strong evidence for its role in neurological conditions. The gene is included on panels for childhood onset hereditary spastic paraplegia, early onset or syndromic epilepsy, and intellectual disability, reflecting the range of presentations associated with AIMP1 variants. It also features on the hereditary spastic paraplegia panel and panels for inherited white matter disorders, supporting its clinical relevance for investigating unexplained neurological symptoms in both paediatric and adult populations.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the AIMP1 protein do in cells?
AIMP1 helps organise the aminoacyl-tRNA synthetase complex, which is essential for accurate protein synthesis, and also participates in cell signalling pathways that regulate proliferation, migration, and responses to cellular stress.
Why do AIMP1 variants affect the nervous system?
The nervous system has particularly high demands for accurate protein production and is sensitive to disruptions in cellular processes that AIMP1 supports. This vulnerability may explain why variants in this gene predominantly cause neurological symptoms.
Is AIMP1 tested in the NHS?
Yes, AIMP1 is included on multiple NHS gene panels for investigating conditions such as hereditary spastic paraplegia, epilepsy, intellectual disability, and white matter disorders when clinical features suggest a genetic cause.