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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TIAL1
TIA1 cytotoxic granule associated RNA binding protein like 1
Chromosome 10 · 10q26.11
NCBI Gene: 7073Ensembl: ENSG00000151923.19HGNC: HGNC:11804UniProt: Q01085
129PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of miRNA-mediated gene silencingmRNA 3'-UTR bindingnegative regulation of cell population proliferationpositive regulation of hippo signalingneurodegenerative diseaseAbnormality of the gastrointestinal tractliver diseaseneoplasm
✦AI Summary

TIAL1 is an RNA-binding protein primarily functioning in alternative pre-mRNA splicing and cytoplasmic stress granule (SG) formation 1. It preferentially binds uridine-rich RNA sequences and regulates alternative splicing of genes including SIRT1, where it promotes exon 8 exclusion 2. TIAL1 acts downstream of stress-induced EIF2S1 phosphorylation to recruit untranslated mRNAs to cytoplasmic SGs 1, a mechanism relevant to chemoresistance in esophageal cancer where TIAL1 enhances stress granule nucleation under cisplatin stress 3. In hepatitis B infection, TIAL1 binds the viral pregenomic RNA at the 5' stem-loop structure to selectively increase polymerase translation while decreasing core protein translation, thereby regulating viral replication balance 4. Disease relevance extends across multiple pathologies: TIAL1 is co-sequestered with TDP-43 in neurodegenerative diseases (ALS, FTLD, Alzheimer's), contributing to aberrant APP splicing and amyloid-beta pathology 5. In skin squamous cell carcinoma, TIAL1 functions downstream of MBNL1 in apoptotic pathways suppressing metastasis 6, while in hepatocellular carcinoma, TIAL1 knockdown restores 5-fluorouracil sensitivity in drug-resistant cells 7. These findings establish TIAL1 as a multifunctional regulator linking RNA processing to stress responses, viral replication, and cancer pathogenesis.

Sources cited
1
TIAL1 functions in nuclear transcription/splicing regulation and cytoplasmic mRNA stability/translation control
PMID: 26036275
2
TIAL1 regulates SIRT1 alternative splicing by promoting exon 8 exclusion
PMID: 24566137
3
TIAL1 participates in stress granule nucleation and cisplatin resistance in esophageal cancer
PMID: 41037404
4
TIAL1 binds hepatitis B pregenomic RNA at the 5' stem-loop to regulate polymerase vs. core protein translation
PMID: 37699883
5
TIAL1 is co-sequestered with TDP-43 in neurodegenerative diseases, contributing to APP splicing dysregulation and amyloid pathology
PMID: 40654715
6
TIAL1 functions downstream of MBNL1 in the TIAL1/MYOD1/Caspase-3 pathway suppressing skin squamous cell carcinoma metastasis
PMID: 33896245
7
TIAL1 knockdown restores 5-fluorouracil sensitivity in drug-resistant hepatoma cells
PMID: 40087331
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.37Weak
Abnormality of the gastrointestinal tractOpen Targets
0.30Weak
liver diseaseOpen Targets
0.10Weak
neoplasmOpen Targets
0.08Suggestive
gliomaOpen Targets
0.08Suggestive
azoospermiaOpen Targets
0.06Suggestive
primary ovarian insufficiencyOpen Targets
0.06Suggestive
Parkinson diseaseOpen Targets
0.05Suggestive
46,XX gonadal dysgenesisOpen Targets
0.05Suggestive
partial chromosome Y deletionOpen Targets
0.05Suggestive
ring chromosome YOpen Targets
0.04Suggestive
46,XY complete gonadal dysgenesisOpen Targets
0.04Suggestive
Testicular regression syndromeOpen Targets
0.04Suggestive
spinocerebellar ataxia type 32Open Targets
0.04Suggestive
isochromosomy YpOpen Targets
0.04Suggestive
spermatogenic failure 25Open Targets
0.04Suggestive
spermatogenic failure 57Open Targets
0.04Suggestive
spermatogenic failure 50Open Targets
0.04Suggestive
46,XX testicular disorder of sex developmentOpen Targets
0.04Suggestive
spermatogenic failure, X-linked, 2Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
FUSProtein interaction100%EIF4EProtein interaction100%EIF4G1Protein interaction100%EIF3BProtein interaction100%HNRNPA1Protein interaction100%EIF4A2Protein interaction99%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
81%
Lung
72%
Liver
61%
Brain
58%
Heart
52%
Gene Interaction Network
Click a node to explore
TIAL1FUSEIF4EEIF4G1EIF3BHNRNPA1EIF4A2
PROTEIN STRUCTURE
Preparing viewer…
PDB1X4G · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.21Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.11 [0.06–0.21]
RankingsWhere TIAL1 stands among ~20K protein-coding genes
  • #3,638of 20,598
    Most Researched129 · top quartile
  • #525of 17,882
    Most Constrained (LOEUF)0.21 · top 5%
Genes detectedTIAL1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
RNA binding protein TIAR modulates HBV replication by tipping the balance of pgRNA translation.
PMID: 37699883
Signal Transduct Target Ther · 2023
1.00
2
USP39/SMC4 promotes hepatoma cell proliferation and 5-FU resistance.
PMID: 40087331
Sci Rep · 2025
0.90
3
TDP-43 toxic gain of function links ALS, FTD and Alzheimer's Disease through splicing dysregulation.
PMID: 40654715
bioRxiv · 2025
0.80
4
T-cell intracellular antigens in health and disease.
PMID: 26036275
Cell Cycle · 2015
0.70
5
HuR and TIA1/TIAL1 are involved in regulation of alternative splicing of SIRT1 pre-mRNA.
PMID: 24566137
Int J Mol Sci · 2014
0.60