TPSAB1
protein-codingtryptase alpha/beta 1
Gene summary
Tryptases comprise a family of trypsin-like serine proteases, the peptidase family S1. Tryptases are enzymatically active only as heparin-stabilized tetramers, and they are resistant to all known endogenous proteinase inhibitors. Several tryptase genes are clustered on chromosome 16p13.3. These genes are characterized by several distinct features. They have a highly conserved 3' UTR and contain tandem repeat sequences at the 5' flank and 3' UTR which are thought to play a role in regulation of the mRNA stability. These genes have an intron immediately upstream of the initiator Met codon, which separates the site of transcription initiation from protein coding sequence. This feature is characteristic of tryptases but is unusual in other genes. The alleles of this gene exhibit an unusual amount of sequence variation, such that the alleles were once thought to represent two separate genes, alpha and beta 1. Beta tryptases appear to be the main isoenzymes expressed in mast cells; whereas in basophils, alpha tryptases predominate. Tryptases have been implicated as mediators in the pathogenesis of asthma and other allergic and inflammatory disorders. [provided by RefSeq, Jul 2008]
- TPSB1
- TPS1
- TPS2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Gastrointestinal; Musculoskeletal; Neurologic
Intervention: General
Rationale: 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
Comments: Reported pathogenic variants have involved gene duplications or triplications
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TPSAB1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003294.4. 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 | 17 | 1 | 18 | |||
| missense | 52 | 12 | 64 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 52 | 29 | 1 | 82 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003285.2 | 5 | MANE Select | |
| Ensembl | ENSP00000343577.3 | 5 | MANE Select | |
| Ensembl | ENSP00000418247.2 | 5 | Standard | |
| Ensembl | ENSP00000418247.2 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Extracellular matrix organization
- Activation of Matrix Metalloproteinases
- Degradation of the extracellular matrix
Biological Process
- proteolysis
- defense response
- extracellular matrix disassembly
Molecular Function
- serine-type endopeptidase activity
- protein binding
- serine-type peptidase activity
Cellular Component
- extracellular region
- extracellular space
- collagen-containing extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000338844
- Coding exons
- 5
- Length
- 1859
- Individuals with no LoFs
- 125578
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 79
- Defined
- 125657
- p
- 0.000314
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -3.13 | 247 | 142 | 1.74 | 0.00000920 | 1694 |
| Missense (PolyPhen) | 85 | 50.925 | 1.6691 | 701 | ||
| Synonymous | -4.38 | 110 | 65.1 | 1.69 | 0.00000483 | 531 |
| Loss of Function | -1.90 | 16 | 9.63 | 1.66 | 5.56e-7 | 104 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00070 | 0.00069 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00039 | 0.00038 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00017 | 0.00014 | rare |
| South Asian | 0.00086 | 0.00085 | rare |
| Other | 0.00036 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type. May play a role in innate immunity. Isoform 2 cleaves large substrates, such as fibronectin, more efficiently than isoform 1, but seems less efficient toward small substrates (PubMed:18854315). {ECO:0000250, ECO:0000250|UniProtKB:P21845, ECO:0000269|PubMed:18854315}.;
Recessive Scores
- pRec
- 0.483
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.233
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |