IARS1 Gene: Isoleucyl-tRNA Synthetase 1
Essential enzyme for protein synthesis, linked to neurodevelopmental disorders and cancer
Gene Information Card
| Symbol | IARS1 |
|---|---|
| Full Name | Isoleucyl-tRNA Synthetase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q22.31 |
| NCBI Gene ID | 3376 ncbi.nlm.nih.gov/gene/3376 |
| Ensembl ID | ENSG00000107175 |
| UniProt ID | P41252 |
| OMIM ID | 600709 |
| HGNC ID | 5330 |
| Aliases | ILRS, IARS, isoleucine--tRNA ligase |
Description
The IARS1 gene encodes isoleucyl-tRNA synthetase 1, a cytoplasmic enzyme that catalyzes the attachment of isoleucine to its cognate tRNA during protein synthesis. This aminoacyl-tRNA synthetase is essential for accurate translation and cellular viability. Mutations in IARS1 are associated with autosomal recessive intellectual disability and growth retardation, and somatic alterations are observed in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, autosomal recessive 60 (MRT60) | Loss-of-function mutations impair isoleucyl-tRNA charging, reducing translation fidelity and neuronal function. | ClinVar, OMIM |
| Growth retardation, impaired intellectual development, hypotonia (GRIDH) | Biallelic missense variants disrupt enzyme activity, leading to multisystem developmental delay. | ClinVar, OMIM |
| Colorectal cancer | Somatic missense mutations and copy number gains may alter translation efficiency, promoting tumorigenesis. | COSMIC |
| Lung adenocarcinoma | Recurrent somatic mutations in IARS1 are reported, potentially affecting protein synthesis in cancer cells. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 18.5 | High |
| Kidney | 14.2 | High |
| Heart | 11.8 | Medium |
| Brain | 8.3 | Medium |
| Lung | 7.1 | Medium |
| Pancreas | 5.6 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 20.1 | Highest expression among tested lines |
| A549 (lung) | 12.4 | Moderate expression |
| HEK293 (embryonic kidney) | 15.0 | High expression |
| K562 (leukemia) | 9.8 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.235G>A (p.Gly79Arg) | Missense | Rare | Loss of function; associated with MRT60 |
| c.986A>G (p.Tyr329Cys) | Missense | Rare | Impaired enzyme activity; GRIDH phenotype |
| c.1574T>C (p.Leu525Pro) | Missense | Rare | Dominant negative effect suspected |
| c.2002C>T (p.Arg668Trp) | Missense | Somatic (0.2% in COSMIC) | Unknown functional impact; observed in colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Biallelic missense or nonsense variants reduce or abolish tRNA charging activity, leading to neurodevelopmental disorders.
Gain of Function (GOF)
Not clearly established; some somatic mutations may increase translation efficiency in cancer.
Dominant Negative (DN)
Rare missense variants (e.g., p.Leu525Pro) may interfere with dimerization or substrate binding, exerting a dominant negative effect.
View complete mutation data：
Gene Ontology (GO)
| • aminoacyl-tRNA synthetase activity | • isoleucine-tRNA ligase activity |
| • ATP binding | • tRNA binding |
| • cytoplasm | • protein biosynthesis |
Pathways
• Aminoacyl-tRNA biosynthesis (KEGG: hsa00970)
• Cytoplasmic translation (Reactome: R-HSA-72766)
Protein Summary
IARS1 is a 1,262-amino-acid cytoplasmic enzyme that belongs to the class I aminoacyl-tRNA synthetase family. It catalyzes the two-step reaction: ATP-dependent activation of isoleucine and its transfer to the 3' end of tRNA(Ile). The protein contains a catalytic domain, an anticodon-binding domain, and a C-terminal domain involved in dimerization. Defects in IARS1 disrupt proteostasis and are linked to neurological and growth disorders.
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