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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia; Welander distal myopathy	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Neurologic	23348830; 28817800; 29216908

ClinVar

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

• not provided (1 variants)
• Welander distal myopathy (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	40	6	48
missense	1		93	3		97
nonsense			2			2
start loss			2			2
frameshift			4			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)			4			4
splice region			9	14	2	25
non coding			6	52	26	84
Total	1	0	114	95	32

Highest pathogenic variant AF is 0.0000197

Variants in TIA1

This is a list of pathogenic ClinVar variants found in the TIA1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-70212723-T-G		Welander distal myopathy	Uncertain significance (May 10, 2022)
2-70212723-TG-T		Welander distal myopathy	Uncertain significance (Sep 04, 2016)
2-70212730-C-T		Welander distal myopathy	Pathogenic (Jan 29, 2024)
2-70212734-C-A		Welander distal myopathy	Likely benign (Aug 31, 2022)
2-70212739-C-T		Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia • Welander distal myopathy	Uncertain significance (Jan 22, 2024)
2-70212756-G-A			Uncertain significance (Jul 01, 2024)
2-70212758-C-T		Welander distal myopathy	Benign/Likely benign (Jan 28, 2024)
2-70212762-T-C		Welander distal myopathy	Uncertain significance (Jul 05, 2022)
2-70212763-T-C		Welander distal myopathy	Uncertain significance (Oct 13, 2023)
2-70212772-T-C		Welander distal myopathy	Uncertain significance (Apr 28, 2023)
2-70212779-A-G		Welander distal myopathy	Benign (Nov 27, 2023)
2-70212779-A-AT		Welander distal myopathy	Uncertain significance (Jul 25, 2022)
2-70212784-G-A		Welander distal myopathy	Uncertain significance (Sep 13, 2019)
2-70212794-C-T		not specified • Welander distal myopathy	Benign/Likely benign (Jan 26, 2024)
2-70212795-G-A		AMYOTROPHIC LATERAL SCLEROSIS 26 WITH FRONTOTEMPORAL DEMENTIA • Welander distal myopathy	Conflicting classifications of pathogenicity (Dec 06, 2023)
2-70212798-T-G		Welander distal myopathy	Uncertain significance (Nov 30, 2022)
2-70212802-C-T		Welander distal myopathy	Conflicting classifications of pathogenicity (Jul 01, 2024)
2-70212808-A-C		Welander distal myopathy	Uncertain significance (Jul 15, 2022)
2-70212810-T-C		Welander distal myopathy • not specified • TIA1-related disorder • Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia	Conflicting classifications of pathogenicity (Jul 01, 2024)
2-70212821-C-A		Welander distal myopathy	Uncertain significance (Sep 15, 2021)
2-70212840-G-A			Uncertain significance (Jul 07, 2021)
2-70212842-C-G		Welander distal myopathy	Uncertain significance (Jul 25, 2022)
2-70212851-G-T		Welander distal myopathy	Likely benign (Nov 14, 2020)
2-70212852-G-A		Welander distal myopathy	Likely benign (Dec 18, 2023)
2-70212853-A-G		Welander distal myopathy	Likely benign (Aug 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TIA1	protein_coding	protein_coding	ENST00000433529	13	39217

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.275	0.725	125737	0	10	125747	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.07	129	214	0.602	0.0000108	2537
Missense in Polyphen		20	50.431	0.39658		608
Synonymous	-0.141	70	68.5	1.02	0.00000347	694
Loss of Function	3.87	7	29.8	0.235	0.00000161	306

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000932	0.0000462
European (Non-Finnish)	0.0000704	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.0000328	0.0000327
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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