TIAL1

Summary

TIAL1 (TIA1 cytotoxic granule associated RNA binding protein like 1, HGNC:11804) is a protein-coding gene on chromosome 10q26.11, encoding Nucleolysin TIAR (Q01085). RNA-binding protein involved in alternative pre-RNA splicing and in cytoplasmic stress granules formation.

The protein encoded by this gene is a member of a family of RNA-binding proteins, has three RNA recognition motifs (RRMs), and binds adenine and uridine-rich elements in mRNA and pre-mRNAs of a wide range of genes. It regulates various activities including translational control, splicing and apoptosis. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. The different isoforms have been show to function differently with respect to post-transcriptional silencing.

Source: NCBI Gene 7073 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 41 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_003252

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11804
Approved symbol	TIAL1
Name	TIA1 cytotoxic granule associated RNA binding protein like 1
Location	10q26.11
Locus type	gene with protein product
Status	Approved
Aliases	TIAR
Ensembl gene	ENSG00000151923
Ensembl biotype	protein_coding
OMIM	603413
Entrez	7073

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 10 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000369086, ENST00000369087, ENST00000369093, ENST00000412524, ENST00000436547, ENST00000462373, ENST00000463089, ENST00000470635, ENST00000470781, ENST00000479729, ENST00000489822, ENST00000495821, ENST00000497671, ENST00000899115, ENST00000899116, ENST00000899117, ENST00000937094, ENST00000937095, ENST00000937096

RefSeq mRNA: 8 — MANE Select: NM_003252 NM_001033925, NM_001323964, NM_001323965, NM_001323967, NM_001323968, NM_001323969, NM_001323970, NM_003252

CCDS: CCDS31295, CCDS7613

Canonical transcript exons

ENST00000436547 — 12 exons

Exon	Start	End
ENSE00001816601	119596434	119596964
ENSE00001903678	119573465	119575791
ENSE00003500462	119581922	119582009
ENSE00003519570	119577080	119577203
ENSE00003579709	119582169	119582223
ENSE00003583639	119576611	119576750
ENSE00003587021	119588152	119588248
ENSE00003603603	119578726	119578834
ENSE00003651234	119582459	119582557
ENSE00003669373	119577641	119577736
ENSE00003680411	119577451	119577535
ENSE00003689522	119579935	119580010

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 97.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 93.6789 / max 501.9633, expressed in 1827 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111697	45.9248	1823
111701	22.9632	1812
111702	10.8774	1773
111703	8.5904	1778
111698	2.5852	1361
111696	1.2463	903
111700	0.8768	550
111699	0.3294	130
111694	0.2775	106
111704	0.0078	3

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.88	gold quality
body of uterus	UBERON:0009853	97.88	gold quality
left ovary	UBERON:0002119	97.67	gold quality
left lobe of thyroid gland	UBERON:0001120	97.62	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.55	gold quality
endocervix	UBERON:0000458	97.54	gold quality
tibia	UBERON:0000979	97.53	gold quality
skin of abdomen	UBERON:0001416	97.51	gold quality
minor salivary gland	UBERON:0001830	97.51	gold quality
right ovary	UBERON:0002118	97.51	gold quality
lymph node	UBERON:0000029	97.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.48	gold quality
right lung	UBERON:0002167	97.44	gold quality
granulocyte	CL:0000094	97.40	gold quality
right lobe of thyroid gland	UBERON:0001119	97.36	gold quality
thyroid gland	UBERON:0002046	97.35	gold quality
gall bladder	UBERON:0002110	97.29	gold quality
mouth mucosa	UBERON:0003729	97.27	gold quality
ectocervix	UBERON:0012249	97.25	gold quality
saliva-secreting gland	UBERON:0001044	97.23	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.22	gold quality
gingival epithelium	UBERON:0001949	97.20	gold quality
skin of leg	UBERON:0001511	97.19	gold quality
rectum	UBERON:0001052	97.18	gold quality
esophagus mucosa	UBERON:0002469	97.18	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.13	gold quality
ganglionic eminence	UBERON:0004023	97.11	gold quality
body of pancreas	UBERON:0001150	97.10	gold quality
esophagus	UBERON:0001043	97.08	gold quality
left uterine tube	UBERON:0001303	97.07	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.39
E-CURD-97	no	704.58
E-GEOD-106540	no	432.94
E-GEOD-124858	no	343.65
E-MTAB-9689	no	218.82
E-MTAB-8060	no	125.56

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
PF4	Unknown

Upstream regulators (CollecTRI, top): PARP1, RUNX3

miRNA regulators (miRDB)

106 targeting TIAL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-9-3P	99.96	70.88	2068
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6835-3P	99.93	70.49	2904

Literature-anchored findings (GeneRIF, showing 32)

• results report the identification of TIAR as a novel player in the regulation of calcitonin/CGRP alternative RNA processing (PMID:12917321)
• activated during HSV-1 infection and accumulated in cytoplasm of cells 6 hr after infection (PMID:15280467)
• HuR, KSRP and TIAR are bound to one or more loci in the 3’UTR of IL-8 in breast cancer cells. (PMID:15514971)
• TIAR seems to be involved in the post-transcriptional regulation of human iNOS expression (PMID:16191398)
• Furthermore, we found that overexpression of DISC1 in SH-SY5Y cells induces the assembly of eIF3- and TIA-1-positive stress granules (SGs), discrete cytoplasmic granules formed in response to environmental stresses. (PMID:16243297)
• TIAR-mediated inhibition of translation factor expression elicits a sustained repression of protein biosynthesis in cells responding to stress. (PMID:16537914)
• TIAL1 maintains cytochrome c biosynthesis. (PMID:16581801)
• adenosine/uridine (AU)-rich element-binding proteins TIA-1 (T-cell intracellular antigen-1), TIAR (TIA-1-related protein), and HuR (Hu antigen R) interact with the beta-F1-ATPase mRNA through an AU-rich sequence located to the 3’-UTR. (PMID:16890199)
• Competitive binding of AUF1 and TIAR to MYC mRNA controls its translation. (PMID:17486099)
• TIAR regulates the relative expression of TIA-1 isoforms. (PMID:17488725)
• Our in vivo data, taken together with previous in vitro results, show that K-SAM splicing activation involves cooperative binding of TIA-1 and U1 snRNP to the exon’s 5’ splice site region. (PMID:17512901)
• Results report the identification of a C-rich signature motif present in TIAR target mRNAs whose association with TIAR decreases following exposure to a stress-causing agent. (PMID:17682065)
• Show increased TIA-1 positive cytotoxic T-lymphocytes in inflamed mucosa of patients with inflammatory bowel disease. (PMID:17869012)
• In contrast with previous assumptions, the mutated residues are buried within the hydrophobic interior of the domain, where they would be likely to destabilize the RRM fold rather than directly inhibit RNA binding. (PMID:18201561)
• Simultaneous knockdown of TIA1 and TIAL1 resulted in increased skipping of alternatively spliced exons associated with U-rich motifs, but did not affect alternatively spliced exons that are not associated with U-rich motifs. (PMID:18456862)
• TIA1 and TIAL1 regulate the alternate splicing of lysyl hydroxylase 2 (PMID:19110540)
• SOD1 sequesters Hu antigen R (HuR) and TIA-1-related protein (TIAR) and has a role in impaired post-transcriptional regulation of vascular endothelial growth factor (PMID:19805546)
• Data show that apoptotic (TIAR and TIA-1) marker expression in thyroid tissues from adolescents with immune thyroid diseases is higher than in non-immune thyroid diseases. (PMID:20675271)
• Severe hypoxia caused co-aggregation of TIAR/TIA-1 and these proteins suppressed HIF-1alpha expression. (PMID:20980400)
• Data show that TIA1 and TIAL1 bind at the same positions on human RNAs, and are consistent with a model where TIA proteins shorten the time available for definition of an alternative exon by enhancing recognition of the preceding 5’ splice site. (PMID:21048981)
• TIA1 and TIAR proteins are intron-associated positive regulators of SMN2 exon 7 splicing. (PMID:21189287)
• findings demonstrate that TIAR recognition motif 2 (RRM2), together with its C-terminal extension, is the major contributor for the high-affinity (nM) interactions of TIAR with target RNA sequences (PMID:23603827)
• TIAL1 inhibition of the exon 8 exclusion led to a decrease in SIRT1-Exon8 mRNA levels. (PMID:24566137)
• TIA proteins can function as long-term regulators of the ACTB mRNA metabolism in mouse and human cells. (PMID:24766723)
• A role for TIAR is identified in T-cells for control of translational specificity. (PMID:24927121)
• results suggest that TIA-1 and TIAR are two new host factors that interact with 5-UTR of EV71 genome and positively regulate viral replication (PMID:26363455)
• we identified MT1JP as a critical factor in restraining cell transformation by modulating p53 translation through interactions with TIAR (PMID:26909858)
• Data suggest that TPD52 (tumor protein D52) and a TPD52 fragment (residues 78-280) along with TIA-1 (T-cell intracellular antigen-1) and TIAR (TIA-1-related protein) contribute to mRNA stability as cis-acting and trans-acting factors; 3prime-untranslated regions of TPD52, TPD53, and TPD54 regulate expression of their respective genes in a post-transcriptional manner by altering mRNA stability. (PMID:28298474)
• Data indicate that both ELAVL1 and TIAR positively regulate endogenous SNCA in vivo. (PMID:29149290)
• Depletion of TIAR accelerates mitotic entry and leads to chromosomal instability in response to replication stress, in a manner that can be alleviated by the concomitant depletion of Cdc25B or inhibition of CDK1. Since TIAR retains CDK1 in GMGs and attenuates CDK1 activity, we propose that the assembly of GMGs may represent a so far unrecognized mechanism that contributes to the activation of the G2/M checkpoint (PMID:30538118)
• The manipulation of miR2233p/TIAL1 interaction may be involved in the neuroprotective effects of DEX. (PMID:30569136)
• RNA binding protein TIAR modulates HBV replication by tipping the balance of pgRNA translation. (PMID:37699883)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tial1	ENSMUSG00000030846
rattus_norvegicus	Tial1	ENSRNOG00000020271

Paralogs (36): DAZAP1 (ENSG00000071626), CIRBP (ENSG00000099622), RBM23 (ENSG00000100461), RBM3 (ENSG00000102317), NCL (ENSG00000115053), TIA1 (ENSG00000116001), HNRNPA2B1 (ENSG00000122566), RBM19 (ENSG00000122965), RBM39 (ENSG00000131051), MSI1 (ENSG00000135097), HNRNPA1 (ENSG00000135486), HNRNPD (ENSG00000138668), HNRNPA1L2 (ENSG00000139675), RBMX (ENSG00000147274), A1CF (ENSG00000148584), RBM46 (ENSG00000151962), HNRNPDL (ENSG00000152795), MSI2 (ENSG00000153944), RBM47 (ENSG00000163694), RBMY1F (ENSG00000169800), HNRNPA3 (ENSG00000170144), RBMXL2 (ENSG00000170748), RBM4B (ENSG00000173914), RBM4 (ENSG00000173933), RBMXL3 (ENSG00000175718), HNRNPA0 (ENSG00000177733), TRNAU1AP (ENSG00000180098), HNRNPAB (ENSG00000197451), RBMXL1 (ENSG00000213516), HNRNPA1L3 (ENSG00000224578), RBMY1J (ENSG00000226941), RBMY1A1 (ENSG00000234414), RBMY1E (ENSG00000242389), RBMY1B (ENSG00000242875), RBMY1D (ENSG00000244395), DND1 (ENSG00000256453)

Protein

Protein identifiers

Nucleolysin TIAR — Q01085 (reviewed: Q01085)

Alternative names: TIA-1-related protein

All UniProt accessions (5): Q01085, A0A087WX93, A6NKZ9, E7ETC0, E7ETJ9

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein involved in alternative pre-RNA splicing and in cytoplasmic stress granules formation. Shows a preference for uridine-rich RNAs. Activates splicing of alternative exons with weak 5’ splice sites followed by a U-rich stretch on its own pre-mRNA and on TIA1 mRNA. Promotes the inclusion of TIA1 exon 5 to give rise to the long isoform (isoform a) of TIA1. Acts downstream of the stress-induced phosphorylation of EIF2S1/EIF2A to promote the recruitment of untranslated mRNAs to cytoplasmic stress granules (SG). Possesses nucleolytic activity against cytotoxic lymphocyte target cells. May be involved in apoptosis.

Subunit / interactions. Interacts with FASTK.

Subcellular location. Nucleus. Cytoplasm. Cytolytic granule. Stress granule.

Tissue specificity. Expressed in brain, heart, kidney, lung and skeletal muscle.

Post-translational modifications. Phosphorylated by MAPK14 following DNA damage, releasing TIAR from GADD45A mRNA.

Domain organisation. The RRM 2 domain is required for the binding to target RNA, and the RRM 1 and RRM 3 domains seem to contribute to the affinity of the interaction with RNA. The RRM2 domain and the C-terminal residues 290-339 contribute to nuclear localization. The RRM3 domain mediates nuclear export and cytoplasmic localization in a manner dependent on RNA- binding.

Isoforms (2)

UniProt ID	Names	Canonical?
Q01085-1	1	yes
Q01085-2	2

RefSeq proteins (8): NP_001029097, NP_001310893, NP_001310894, NP_001310896, NP_001310897, NP_001310898, NP_001310899, NP_003243* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR003954	RRM_euk-type	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034492	TIAR_RRM1	Domain
IPR034494	TIAR_RRM2	Domain
IPR034496	TIAR_RRM3	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076

UniProt features (33 total): strand 14, helix 7, domain 3, turn 3, modified residue 2, chain 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1X4G	SOLUTION NMR
2CQI	SOLUTION NMR
2DH7	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01085-F1	75.49	0.52

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 122, 201

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-6803529	FGFR2 alternative splicing
R-HSA-162582	Signal Transduction
R-HSA-190236	Signaling by FGFR
R-HSA-5654738	Signaling by FGFR2
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 290 (showing top): MORF_MTA1, CREL_01, AP1_01, YAGI_AML_WITH_INV_16_TRANSLOCATION, GCM_NPM1, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, REACTOME_SIGNALING_BY_FGFR, MORF_UBE2I, MAZ_Q6, MORF_HDAC1, MORF_RAD21, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, MORF_HDAC2, GOBP_HIPPO_SIGNALING, GGAMTNNNNNTCCY_UNKNOWN

GO Biological Process (7): regulation of transcription by RNA polymerase II (GO:0006357), apoptotic process (GO:0006915), defense response (GO:0006952), negative regulation of cell population proliferation (GO:0008285), positive regulation of hippo signaling (GO:0035332), positive regulation of miRNA-mediated gene silencing (GO:2000637), regulation of cell population proliferation (GO:0042127)

GO Molecular Function (7): DNA binding (GO:0003677), RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), protein-RNA adaptor activity (GO:0140517), nucleic acid binding (GO:0003676), mRNA binding (GO:0003729), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), lysosome (GO:0005764), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), cytolytic granule (GO:0044194)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Signaling by FGFR2	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by FGFR	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell population proliferation	2
nucleic acid binding	2
binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
response to stress	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
hippo signaling	1
regulation of hippo signaling	1
positive regulation of intracellular signal transduction	1
miRNA-mediated post-transcriptional gene silencing	1
regulation of miRNA-mediated gene silencing	1
positive regulation of post-transcriptional gene silencing by RNA	1
regulation of cellular process	1
mRNA binding	1
protein-macromolecule adaptor activity	1
RNA binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
lytic vacuole	1
cytoplasm	1
cytoplasmic ribonucleoprotein granule	1
lysosome	1

Protein interactions and networks

STRING

2792 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TIAL1	G3BP1	Q13283	995
TIAL1	TIA1	P31483	982
TIAL1	ELAVL1	Q15717	945
TIAL1	EIF4G1	Q04637	895
TIAL1	FMR1	Q06787	886
TIAL1	EIF3B	P55884	860
TIAL1	CAPRIN1	Q14444	842
TIAL1	EIF4E	P06730	839
TIAL1	SAMD4A	Q9UPU9	809
TIAL1	DCP1A	Q9NPI6	797
TIAL1	STAU1	O95793	785
TIAL1	DDX6	P26196	764
TIAL1	EIF4A1	P04765	762
TIAL1	FUS	P35637	739
TIAL1	FASTK	Q14296	726

IntAct

79 interactions, top by confidence:

A	B	Type	Score
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
TARDBP	PPP1R15A	psi-mi:“MI:0914”(association)	0.600
DZIP3	TIAL1	psi-mi:“MI:0915”(physical association)	0.590
TIAL1	TARDBP	psi-mi:“MI:0403”(colocalization)	0.580
SAV1	SEMG1	psi-mi:“MI:0914”(association)	0.530
TIAL1	TRO	psi-mi:“MI:0914”(association)	0.530
MOV10	TIAL1	psi-mi:“MI:0915”(physical association)	0.500
TIAL1	SMN1	psi-mi:“MI:0403”(colocalization)	0.460
TIAL1	SMN1	psi-mi:“MI:0915”(physical association)	0.460
BNLF1	TIAL1	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
CUL4A	HAX1	psi-mi:“MI:0914”(association)	0.350
DCUN1D1	RGSL1	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
CUL2	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
CUL4B	APBB1	psi-mi:“MI:0914”(association)	0.350
NEDD8	DDX3X	psi-mi:“MI:0914”(association)	0.350
COPS6	DDX3X	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
CUL5	DDX3X	psi-mi:“MI:0914”(association)	0.350
SOX2	CBX4	psi-mi:“MI:0914”(association)	0.350

BioGRID (191): TIAL1 (Affinity Capture-MS), TIAL1 (Affinity Capture-MS), TIAL1 (Affinity Capture-MS), CCDC58 (Co-fractionation), PCBP1 (Co-fractionation), PCBP2 (Co-fractionation), PTRHD1 (Co-fractionation), TIAL1 (Co-fractionation), TIAL1 (Co-fractionation), TIAL1 (Co-fractionation), TIAL1 (Co-fractionation), TIAL1 (Co-fractionation), TIAL1 (Co-fractionation), TIAL1 (Co-fractionation), TIAL1 (Co-fractionation)

ESM2 similar proteins: A2Q848, F4I3B3, O01671, O22173, O60176, P16914, P17225, P23241, P26599, P31483, P32588, P42731, P52912, P70318, Q00438, Q00539, Q01085, Q09702, Q0J9Y2, Q0V9L3, Q0WW84, Q1RMJ7, Q28F51, Q29099, Q2R0Q1, Q4KM14, Q5R462, Q6YZW2, Q7TSY6, Q80VC6, Q8CIN6, Q8GZ26, Q8LFS6, Q8VXZ9, Q8WN55, Q93W34, Q95QV8, Q9BJZ5, Q9FPJ8, Q9FXA2

Diamond homologs: A0A0A0LLY1, A0A0D1C8Z4, A0A2R8Y4L2, A5A6H4, A5A6M3, A7VJC2, D4AE41, O22703, O75526, O88569, O89086, O93235, P04256, P09651, P09867, P10979, P17130, P19682, P19683, P19684, P22626, P28644, P38159, P39697, P41891, P49310, P49311, P49312, P49313, P49314, P51968, P51989, P51990, P51991, P51992, P60824, P60825, P60826, P84586, P98179

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RUNX3	“down-regulates quantity by repression”	TIAL1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Macroautophagy	5	10.7×	9e-03
Neddylation	11	9.7×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
intrinsic apoptotic signaling pathway	6	33.1×	6e-06
autophagosome maturation	5	27.0×	1e-04
mitophagy	5	24.5×	2e-04
G1/S transition of mitotic cell cycle	6	18.5×	1e-04
autophagosome assembly	5	17.3×	8e-04
protein ubiquitination	9	5.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

41 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	17
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
441987	GRCh37/hg19 10p15.3-q26.3(chr10:100027-135427143)	Pathogenic

SpliceAI

2181 predictions. Top by Δscore:

Variant	Effect	Δscore
10:119575793:T:C	acceptor_gain	1.0000
10:119576603:CAACT:C	donor_loss	1.0000
10:119576604:AACTT:A	donor_loss	1.0000
10:119576605:ACTT:A	donor_loss	1.0000
10:119576606:CT:C	donor_loss	1.0000
10:119576607:TTAC:T	donor_loss	1.0000
10:119576608:TA:T	donor_loss	1.0000
10:119576609:A:AC	donor_gain	1.0000
10:119576609:A:C	donor_loss	1.0000
10:119576610:C:CC	donor_gain	1.0000
10:119576610:C:T	donor_loss	1.0000
10:119576610:CT:C	donor_gain	1.0000
10:119576610:CTCT:C	donor_gain	1.0000
10:119576610:CTCTA:C	donor_gain	1.0000
10:119576746:TCAAC:T	acceptor_gain	1.0000
10:119576747:CAAC:C	acceptor_gain	1.0000
10:119576747:CAACC:C	acceptor_gain	1.0000
10:119576751:C:CA	acceptor_loss	1.0000
10:119576751:C:CC	acceptor_gain	1.0000
10:119577076:TTA:T	donor_loss	1.0000
10:119577077:TAC:T	donor_loss	1.0000
10:119577078:A:T	donor_loss	1.0000
10:119577199:AAAAT:A	acceptor_gain	1.0000
10:119577200:AAAT:A	acceptor_gain	1.0000
10:119577201:AAT:A	acceptor_gain	1.0000
10:119577202:AT:A	acceptor_gain	1.0000
10:119577204:C:CC	acceptor_gain	1.0000
10:119577205:T:C	acceptor_loss	1.0000
10:119577445:TGTTA:T	donor_loss	1.0000
10:119577446:GTTAC:G	donor_loss	1.0000

AlphaMissense

2482 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:119577117:C:A	G275V	1.000
10:119577117:C:T	G275D	1.000
10:119577118:C:A	G275C	1.000
10:119577118:C:G	G275R	1.000
10:119577119:C:A	W274C	1.000
10:119577119:C:G	W274C	1.000
10:119577120:C:G	W274S	1.000
10:119577121:A:G	W274R	1.000
10:119577121:A:T	W274R	1.000
10:119577125:G:C	C272W	1.000
10:119577126:C:T	C272Y	1.000
10:119577127:A:G	C272R	1.000
10:119577130:T:C	K271E	1.000
10:119577132:A:T	V270D	1.000
10:119577171:A:T	I257N	1.000
10:119577174:G:T	A256D	1.000
10:119577175:C:G	A256P	1.000
10:119577180:G:T	A254D	1.000
10:119577181:C:G	A254P	1.000
10:119577183:G:T	A253E	1.000
10:119577454:A:T	V245D	1.000
10:119577456:A:C	F244L	1.000
10:119577456:A:T	F244L	1.000
10:119577457:A:C	F244C	1.000
10:119577457:A:G	F244S	1.000
10:119577458:A:C	F244V	1.000
10:119577458:A:G	F244L	1.000
10:119577458:A:T	F244I	1.000
10:119577461:A:G	S243P	1.000
10:119577464:A:C	Y242D	1.000

dbSNP variants (sampled 300 via entrez): RS1000047430 (10:119583780 C>G), RS1000166312 (10:119575261 G>A), RS1000431168 (10:119590798 A>G), RS1000500974 (10:119573585 G>C), RS1000651334 (10:119582083 G>A), RS1000660400 (10:119589622 GT>G,GTT), RS1000781000 (10:119590989 T>A), RS1000815374 (10:119594895 T>C), RS1000910895 (10:119595674 C>G,T), RS1001291542 (10:119574899 T>C,G), RS1001321880 (10:119595401 C>G,T), RS1001340438 (10:119575943 A>C,G), RS1001362182 (10:119584784 G>A), RS1001655211 (10:119596753 A>G), RS1001756848 (10:119596396 C>T)

Disease associations

OMIM: gene MIM:603413 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003444_2	Response to carboplatin and paclitaxel in ovarian cancer (MTT IC50)	7.000000e-07
GCST003835_1	Depressive symptoms (stressful life events interaction)	4.000000e-08
GCST003984_9	Parkinson’s disease	3.000000e-11
GCST90002394_458	Monocyte percentage of white cells	2.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006952	cytotoxicity measurement
EFO:0007006	depressive symptom measurement
EFO:0007781	stressful life event measurement
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066512 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.96	Kd	1.1	nM	CHEMBL5653589
8.89	ED50	1.286	nM	CHEMBL5653589
6.10	Kd	799.2	nM	CHEMBL3752910
6.03	ED50	934	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149587: Binding affinity to human TIAL1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0011	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149587: Binding affinity to human TIAL1 incubated for 45 mins by Kinobead based pull down assay	kd	0.7993	uM

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, increases methylation, affects cotreatment, affects expression (+1 more)	4
sodium arsenite	affects expression, affects cotreatment, decreases expression, increases abundance, affects splicing	3
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance, affects splicing	3
Valproic Acid	affects expression, increases expression	2
GSK-J4	increases expression	1
ginger extract	affects cotreatment, affects expression, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
trichostatin A	affects expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression, increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Decitabine	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Catechin	affects cotreatment, decreases expression	1
Dactinomycin	affects cotreatment, increases secretion	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652629	Binding	Binding affinity to human TIAL1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2IK	Abcam HeLa TIAL1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.