TIA1 Cytotoxic Granule Associated RNA Binding Protein
A key regulator of RNA metabolism and stress granule assembly, implicated in neurodegeneration and myopathy.
Gene Information Card
| Symbol | TIA1 |
|---|---|
| Full Name | TIA1 cytotoxic granule associated RNA binding protein |
| Gene Type | protein-coding |
| Chromosomal Location | 2p13.3 |
| NCBI Gene ID | 7072 ncbi.nlm.nih.gov/gene/7072 |
| Ensembl ID | ENSG00000116001 |
| UniProt ID | P31483 |
| OMIM ID | 603518 |
| HGNC ID | 11802 |
| Aliases | TIA-1, WDM, TIAL1 (formerly) |
Description
TIA1 encodes a member of the RRM (RNA recognition motif) family of RNA-binding proteins. It is involved in alternative pre-mRNA splicing and is a key component of cytoplasmic stress granules, which form in response to cellular stress. TIA1 regulates translation by binding to AU-rich elements in the 3' UTR of target mRNAs. Mutations in TIA1 are associated with amyotrophic lateral sclerosis (ALS) and Welander distal myopathy (WDM).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Amyotrophic Lateral Sclerosis (ALS) | Gain-of-function mutations in TIA1 promote aberrant stress granule assembly and aggregation, leading to motor neuron toxicity. | ClinVar, OMIM |
| Welander Distal Myopathy (WDM) | Missense mutations in TIA1 impair RNA binding and stress granule dynamics, causing muscle fiber degeneration. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Muscle | 8.2 | Low |
| Heart | 10.1 | Medium |
| Liver | 6.4 | Low |
| Lung | 9.8 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.3 | High expression |
| SH-SY5Y | 13.7 | Neuronal cell line |
| HEK293 | 11.2 | Moderate expression |
| A549 | 9.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Asp15Gly | Missense | Rare (ALS) | Alters RNA binding and promotes stress granule aggregation |
| p.Glu384Lys | Missense | Rare (WDM) | Impairs stress granule disassembly |
| p.Asn357Ser | Missense | Rare (ALS) | Enhances phase separation propensity |
Mutation functional classification
Loss of Function (LOF)
Not clearly established; most pathogenic mutations are gain-of-function or dominant-negative.
Gain of Function (GOF)
ALS-associated mutations (e.g., p.Asp15Gly) increase stress granule formation and aggregation.
Dominant Negative (DN)
WDM-associated mutations (e.g., p.Glu384Lys) disrupt normal stress granule dynamics.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding (GO:0003723) | • mRNA binding (GO:0003729) |
| • stress granule assembly (GO:0034063) | • regulation of alternative mRNA splicing (GO:0000381) |
| • cytoplasmic stress granule (GO:0010494) |
Pathways
• Stress granule formation (Reactome: R-HSA-9711123)
• Regulation of mRNA stability by AU-rich elements (Reactome: R-HSA-450531)
Protein Summary
The TIA1 protein (40 kDa) contains three N-terminal RNA recognition motifs (RRMs) and a C-terminal prion-like domain (PLD). It shuttles between nucleus and cytoplasm, binding to AU-rich elements to regulate splicing and translation. Under stress, TIA1 nucleates stress granules via its PLD, a process dysregulated in ALS and myopathy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TIA1 Knockout HEK293 Cell Line | EDJ-KQ50686 | Human | 7072 | Details Get a Quote |
| TIA1 Knockout HeLa Cell Line | EDJ-KQ54659 | Human | 7072 | Details Get a Quote |
| TIA1 Knockout A-549 Cell Line | EDJ-KQ63139 | Human | 7072 | Details Get a Quote |
| TIA1 Knockout HCT 116 Cell Line | EDJ-KQ71613 | Human | 7072 | Details Get a Quote |
