TIRAP

TIR domain containing adaptor protein, the group of TIR domain containing

Basic information

Region (hg38): 11:126282497-126298845

Links

ENSG00000150455 ∙ NCBI:114609 ∙ OMIM:606252 ∙ HGNC:17192 ∙ Uniprot:P58753 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TIRAP 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	2
missense			10	1	2	13
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					5	5
Total	0	0	10	1	9

Variants in TIRAP

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

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

Position	Type	Phenotype	Significance	ClinVar
11-126290792-A-G		not specified	Benign (Jan 24, 2024)
11-126290892-G-A		TIRAP-related disorder	Likely benign (Dec 01, 2023)
11-126290942-G-A		TIRAP-related disorder	Likely benign (Sep 08, 2023)
11-126290942-G-T		not specified	Uncertain significance (Feb 05, 2024)
11-126291595-T-C		not specified	Benign (Jan 24, 2024)
11-126292477-A-G		not specified	Uncertain significance (Jun 28, 2024)
11-126292573-G-A		not specified • TIRAP-related disorder	Benign (Jan 24, 2024)
11-126292624-C-A		not specified	Uncertain significance (Dec 20, 2023)
11-126292639-G-A		not specified	Uncertain significance (Oct 27, 2023)
11-126292695-G-A			Likely benign (-)
11-126292712-G-A		not specified	Benign (Jan 24, 2024)
11-126292785-G-C		not specified	Uncertain significance (Dec 01, 2022)
11-126292802-C-T		TIRAP-related disorder	Benign (Jan 23, 2024)
11-126292811-C-G		not specified	Uncertain significance (Dec 15, 2023)
11-126292919-G-A		TIRAP-related disorder	Likely benign (Aug 26, 2019)
11-126292948-C-T		Invasive pneumococcal disease, protection against • Malaria, resistance to • Mycobacterium tuberculosis, protection against • Bacteremia, susceptibility • Malaria, susceptibility to;Mycobacterium tuberculosis, susceptibility to;Bacteremia, susceptibility to, 1 • not specified	Benign (Jan 24, 2024)
11-126292967-C-T		not specified	Benign (Jan 24, 2024)
11-126293010-G-C		not specified	Uncertain significance (Oct 05, 2023)
11-126293080-G-A		not specified	Uncertain significance (May 31, 2023)
11-126293085-C-T		not specified	Uncertain significance (Feb 28, 2024)
11-126293091-T-G			Likely benign (-)
11-126293110-T-A		not specified	Uncertain significance (Jul 27, 2024)
11-126293229-C-T		not specified	Benign (Jan 24, 2024)
11-126293717-T-G		not specified	Benign (Jan 24, 2024)
11-126293796-A-G		not specified	Benign (Jan 24, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TIRAP	protein_coding	protein_coding	ENST00000392678	2	15781

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000761	0.549	125584	0	129	125713	0.000513

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.274	149	140	1.07	0.00000861	1498
Missense in Polyphen		65	57.444	1.1315		601
Synonymous	-0.306	65	61.9	1.05	0.00000409	504
Loss of Function	0.379	5	6.00	0.833	2.60e-7	66

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00134	0.00129
Ashkenazi Jewish	0.000497	0.000496
East Asian	0.000109	0.000109
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000362	0.000334
Middle Eastern	0.000109	0.000109
South Asian	0.00161	0.00154
Other	0.000498	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adapter involved in TLR2 and TLR4 signaling pathways in the innate immune response. Acts via IRAK2 and TRAF-6, leading to the activation of NF-kappa-B, MAPK1, MAPK3 and JNK, and resulting in cytokine secretion and the inflammatory response. Positively regulates the production of TNF-alpha and interleukin-6. {ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:19509286}.
• Pathway: Pertussis - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Hepatitis B - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;AGE-RAGE pathway;TLR4 Signaling and Tolerance;Toll-like Receptor Signaling;Fibrin Complement Receptor 3 Signaling Pathway;Toll-like Receptor Signaling Pathway;RAGE;toll-like receptor pathway;Toll-Like Receptors Cascades;Innate Immune System;Immune System;Adaptive Immune System;inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages;Antigen processing-Cross presentation;Class I MHC mediated antigen processing & presentation;ER-Phagosome pathway;Toll Like Receptor 4 (TLR4) Cascade;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;Endogenous TLR signaling (Consensus)

Recessive Scores

• pRec: 0.411

Intolerance Scores

• loftool: 0.816
• rvis_EVS: 1.06
• rvis_percentile_EVS: 91.51

Haploinsufficiency Scores

• pHI: 0.122
• hipred: Y
• hipred_score: 0.541
• ghis: 0.425

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tirap
• Phenotype: homeostasis/metabolism phenotype; immune 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype

Gene ontology

• Biological process: MyD88-dependent toll-like receptor signaling pathway;inflammatory response;cell surface receptor signaling pathway;activation of NF-kappaB-inducing kinase activity;myeloid cell differentiation;positive regulation of B cell proliferation;response to lipopolysaccharide;regulation of interferon-beta production;positive regulation of interleukin-12 production;positive regulation of interleukin-15 production;positive regulation of interleukin-8 production;positive regulation of tumor necrosis factor production;positive regulation of toll-like receptor 2 signaling pathway;positive regulation of toll-like receptor 3 signaling pathway;positive regulation of toll-like receptor 4 signaling pathway;TIRAP-dependent toll-like receptor 4 signaling pathway;positive regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of growth of symbiont in host;innate immune response;regulation of innate immune response;positive regulation of interleukin-6 biosynthetic process;positive regulation of JNK cascade;defense response to Gram-positive bacterium;positive regulation of NF-kappaB transcription factor activity;positive regulation of ERK1 and ERK2 cascade;3'-UTR-mediated mRNA stabilization;cellular response to bacterial lipopeptide;cellular response to lipoteichoic acid;positive regulation of neutrophil chemotaxis;positive regulation of protein homodimerization activity;positive regulation of chemokine (C-X-C motif) ligand 1 production;positive regulation of chemokine (C-X-C motif) ligand 2 production
• Cellular component: cytoplasm;cytosol;plasma membrane;endocytic vesicle;ruffle membrane
• Molecular function: protein kinase C binding;protein binding;phosphatidylinositol-4,5-bisphosphate binding;protein binding, bridging;Toll-like receptor 4 binding;Toll-like receptor 2 binding;identical protein binding;protein homodimerization activity;protein heterodimerization activity