TIRAP
protein-codingTIR domain containing adaptor protein, the group of TIR domain containing
Gene summary
The innate immune system recognizes microbial pathogens through Toll-like receptors (TLRs), which identify pathogen-associated molecular patterns. Different TLRs recognize different pathogen-associated molecular patterns and all TLRs have a Toll-interleukin 1 receptor (TIR) domain, which is responsible for signal transduction. The protein encoded by this gene is a TIR adaptor protein involved in the TLR4 signaling pathway of the immune system. It activates NF-kappa-B, MAPK1, MAPK3 and JNK, which then results in cytokine secretion and the inflammatory response. Alternative splicing of this gene results in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TIRAP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001318777.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | 6 | ||||
| missense | 17 | 2 | 19 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 18 | 8 | 0 | 26 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001305706.1 | 3 | MANE Select | |
| Ensembl | ENSP00000376446.1 | 3 | MANE Select | |
| RefSeq | NP_001034750.1 | 3 | Standard | |
| RefSeq | NP_001305705.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
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
Molecular Function
- protein kinase C binding
- protein binding
- phosphatidylinositol-4,5-bisphosphate binding
- protein binding, bridging
- Toll-like receptor 4 binding
Cellular Component
- cytoplasm
- cytosol
- plasma membrane
- endocytic vesicle
- ruffle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000392678
- Coding exons
- 2
- Length
- 15781
- Individuals with no LoFs
- 125584
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 129
- Defined
- 125713
- p
- 0.000513
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.274 | 149 | 140 | 1.07 | 0.00000861 | 1498 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00067 | 0.00062 | rare |
| Latino/Admixed American | 0.00067 | 0.00067 | rare |
| Ashkenazi Jewish | 0.00050 | 0.00050 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00036 | 0.00033 | rare |
| South Asian | 0.0016 | 0.0015 | notable |
| Other | 0.00050 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.411
Intolerance Scores
- LoFtool
- 0.816
- RVIS EVS
- 1.06
- RVIS percentile EVS
- 91.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |