GeneBe

TIA1

TIA1 cytotoxic granule associated RNA binding protein, the group of RNA binding motif containing

Basic information

Region (hg38): 2:70209444-70248660

Links

ENSG00000116001 ∙ NCBI:7072 ∙ OMIM:603518 ∙ HGNC:11802 ∙ Uniprot:P31483 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • distal myopathy, Welander type (Supportive), mode of inheritance: AD
  • amyotrophic lateral sclerosis 26 with or without frontotemporal dementia (Limited), mode of inheritance: Unknown
  • distal myopathy, Welander type (Strong), mode of inheritance: AD
  • amyotrophic lateral sclerosis 26 with or without frontotemporal dementia (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia; Welander distal myopathyADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingMusculoskeletal; Neurologic23348830; 28817800; 29216908

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TIA1 gene.

  • Welander_distal_myopathy (239 variants)
  • not_provided (67 variants)
  • Inborn_genetic_diseases (14 variants)
  • not_specified (10 variants)
  • Amyotrophic_lateral_sclerosis_26_with_or_without_frontotemporal_dementia (5 variants)
  • TIA1-related_disorder (2 variants)
  • AMYOTROPHIC_LATERAL_SCLEROSIS_26_WITH_FRONTOTEMPORAL_DEMENTIA (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TIA1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000022173.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
48
clinvar
6
clinvar
 55
missense
2
clinvar
107
clinvar
7
clinvar
 116
nonsense
2
clinvar
 2
start loss
2
 2
frameshift
4
clinvar
 4
splice donor/acceptor (+/-2bp)
7
clinvar
 7
Total 0 2 123 55 6

Highest pathogenic variant AF is 0.000021712023

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
TIA1protein_codingprotein_codingENST00000433529 1339217
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.2750.7251257370101257470.0000398
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.071292140.6020.00001082537
Missense in Polyphen2050.4310.39658608
Synonymous-0.1417068.51.020.00000347694
Loss of Function3.87729.80.2350.00000161306

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.00009320.0000462
European (Non-Finnish)0.00007040.0000703
Middle Eastern0.000.00
South Asian0.00003280.0000327
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Involved in alternative pre-RNA splicing and regulation of mRNA translation by binding to AU-rich elements (AREs) located in mRNA 3' untranslated regions (3' UTRs). Possesses nucleolytic activity against cytotoxic lymphocyte target cells. May be involved in apoptosis.;
Disease
DISEASE: Welander distal myopathy (WDM) [MIM:604454]: An autosomal dominant disorder characterized by adult onset of distal muscle weakness predominantly affecting the distal long extensors of the hands, with slow progression to involve all small hand muscles and the lower legs. Skeletal muscle biopsy shows myopathic changes and prominent rimmed vacuoles. Rare homozygous patients showed earlier onset, faster progression, and proximal muscle involvement. {ECO:0000269|PubMed:23348830, ECO:0000269|PubMed:23401021}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
FGFR2 alternative splicing;Signaling by FGFR2;Signal Transduction;Signaling by FGFR;Signaling by Receptor Tyrosine Kinases (Consensus)

Recessive Scores

pRec
0.263

Intolerance Scores

loftool
0.354
rvis_EVS
0.24
rvis_percentile_EVS
69.21

Haploinsufficiency Scores

pHI
0.908
hipred
Y
hipred_score
0.627
ghis
0.585

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.996

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Tia1
Phenotype
immune system phenotype; skeleton phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype;

Gene ontology

Biological process
apoptotic process;fibroblast growth factor receptor signaling pathway;negative regulation of translation;negative regulation of cytokine biosynthetic process;regulation of mRNA splicing, via spliceosome;protein localization to cytoplasmic stress granule;positive regulation of epithelial cell apoptotic process
Cellular component
nucleoplasm;cytoplasm;cytosol;cytoplasmic stress granule;nuclear stress granule
Molecular function
RNA binding;protein binding;poly(A) binding;AU-rich element binding