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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TIA1
TIA1 cytotoxic granule associated RNA binding protein
Chromosome 2 · 2p13.3
NCBI Gene: 7072Ensembl: ENSG00000116001.17HGNC: HGNC:11802UniProt: E5RGV5
160PubMed Papers
22Diseases
0Drugs
1Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolcytoplasmic stress granulenuclear stress granuleprotein bindingamyotrophic lateral sclerosis 26 with or without frontotemporal dementiadistal myopathy, Welander typeAbnormality of the skeletal systemgenetic disorder
✦AI Summary

TIA1 is a cytotoxic granule-associated RNA binding protein that functions primarily as a regulator of stress granule (SG) assembly and RNA metabolism 1. As a core SG component, TIA1 binds RNA through its low-complexity domain and regulates alternative mRNA splicing and translational control, particularly of transcripts containing U-rich elements 2. Under stress conditions, TIA1 promotes phase separation and SG formation, which can stabilize or sequester specific mRNAs from degradation 2. Pathogenic TIA1 mutations in the low-complexity domain are associated with amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia 1. These mutations enhance phase separation propensity, delay stress granule disassembly, and promote TDP-43 accumulation in SGs, contributing to neurodegeneration 1. In ALS models, elevated TIA1 mediates SG formation that sequesters heat shock protein 70 (HSP70) mRNA, impairing protein quality control and exacerbating disease 3. Additionally, TIA1 variants cause Welander distal myopathy, either alone or through digenic inheritance with SQSTM1 polymorphisms 4. Beyond neurodegeneration, TIA1 regulates cellular stress responses including mitochondrial dynamics and senescence through miR-30-5p-mediated expression changes 5. TIA1 also interacts with SARS-CoV-2 RNA elements, suggesting roles in viral regulation 6.

Sources cited
1
TIA1 mutations in ALS/FTD increase phase separation propensity, delay stress granule disassembly, and promote TDP-43 accumulation
PMID: 28817800
2
TIA1 is associated with autosomal dominant distal myopathy and digenic Welander-like distal myopathy with SQSTM1
PMID: 33458580
3
TIA1 forms complexes to recruit and stabilize U-rich mRNAs within stress granules
PMID: 40774970
4
TIA1-mediated stress granules sequester HSP70 mRNA, impairing protein quality control in ALS
PMID: 40622676
5
miR-30-5p regulates TIA1 expression to control mitochondrial dynamics and cellular senescence
PMID: 38858355
6
TIA1 protein binds SARS-CoV-2 RNA stem-loop elements with structural specificity
PMID: 37349329
Disease Associationsⓘ22
amyotrophic lateral sclerosis 26 with or without frontotemporal dementiaOpen Targets
0.66Moderate
distal myopathy, Welander typeOpen Targets
0.65Moderate
Abnormality of the skeletal systemOpen Targets
0.49Moderate
genetic disorderOpen Targets
0.19Weak
neoplasmOpen Targets
0.11Weak
osteoarthritisOpen Targets
0.09Suggestive
tauopathyOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
amyotrophic lateral sclerosisOpen Targets
0.08Suggestive
esophageal squamous cell carcinomaOpen Targets
0.07Suggestive
chondrocalcinosis 2Open Targets
0.07Suggestive
HypercholesterolemiaOpen Targets
0.05Suggestive
liver cancerOpen Targets
0.05Suggestive
glycoprotein storage diseaseOpen Targets
0.05Suggestive
neuromuscular diseaseOpen Targets
0.05Suggestive
Ehlers-Danlos syndrome, musculocontractural typeOpen Targets
0.05Suggestive
liver neoplasmOpen Targets
0.05Suggestive
Angel-shaped phalango-epiphyseal dysplasiaOpen Targets
0.04Suggestive
muscular dystrophyOpen Targets
0.04Suggestive
Amyotrophic lateral sclerosis 26, with or without frontotemporal dementiaUniProt
Welander distal myopathyUniProt
Pathogenic Variants1
NM_022173.4(TIA1):c.1150G>A (p.Glu384Lys)Pathogenic
not provided|Welander distal myopathy
★★☆☆2025→ Residue 384
View on ClinVar ↗
Related Genes
EIF3BProtein interaction100%HNRNPA2B1Protein interaction100%HNRNPA1Protein interaction100%MATR3Protein interaction100%LSM4Protein interaction99%G3BP1Protein interaction98%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
46%
Heart
44%
Liver
43%
Lung
41%
Brain
24%
Gene Interaction Network
Click a node to explore
TIA1EIF3BHNRNPA2B1HNRNPA1MATR3LSM4G3BP1
PROTEIN STRUCTURE
Preparing viewer…
PDB7VI4 · 0.95 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.52Moderately Constrained
pLIⓘ
0.95Intolerant
Observed/Expected LoF0.35 [0.24–0.52]
RankingsWhere TIA1 stands among ~20K protein-coding genes
  • #2,819of 20,598
    Most Researched160 · top quartile
  • #4,766of 5,498
    Most Pathogenic Variants1
  • #3,177of 17,882
    Most Constrained (LOEUF)0.52 · top quartile
Genes detectedTIA1
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
Panorama of the distal myopathies.
PMID: 33458580
Acta Myol · 2020
1.00
2
TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.
PMID: 28817800
Neuron · 2017
0.90
3
Membrane Atg8ylation, stress granule formation, and MTOR regulation during lysosomal damage.
PMID: 36394332
Autophagy · 2023
0.80
4
Functional amyloid protein FXR1 is recruited into neuronal stress granules.
PMID: 40411539
Prion · 2025
0.72
5
TIA1-mediated stress granules promote neurodegeneration by sequestering HSP70 mRNA in C9orf72 mice.
PMID: 40622676
Brain · 2025
0.70