TPSD1
protein-codingtryptase delta 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. Although this gene may be an exception, most of the tryptase 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. Tryptases have been implicated as mediators in the pathogenesis of asthma and other allergic and inflammatory disorders. This gene was once considered to be a pseudogene, although it is now believed to be a functional gene that encodes a protein. [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 ~2.9 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 TPSD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012217.3. 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 | 2 | 1 | 3 | |||
| missense | 66 | 5 | 1 | 72 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 68 | 5 | 2 | 75 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036349.1 | 5 | MANE Select | |
| Ensembl | ENSP00000211076.3 | 5 | MANE Select | |
| Ensembl | ENSP00000380668.2 | 5 | Standard | |
| Ensembl | ENSP00000380668.2 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- proteolysis
Molecular Function
- serine-type endopeptidase activity
- serine-type peptidase activity
Cellular Component
- extracellular space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000211076
- Coding exons
- 5
- Length
- 2473
- Individuals with no LoFs
- 74442
- Homozygous LoFs
- 8009
- Heterozygous LoFs
- 43240
- Defined
- 125691
- p
- 0.230
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.62 | 208 | 152 | 1.37 | 0.00000971 | 1502 |
| Missense (PolyPhen) | 69 | 54.576 | 1.2643 | 598 | ||
| Synonymous | -2.47 | 98 | 71.4 | 1.37 | 0.00000529 | 466 |
| Loss of Function | -0.946 | 15 | 11.5 | 1.30 | 5.97e-7 | 104 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.37 | 0.37 | notable |
| Latino/Admixed American | 0.39 | 0.39 | notable |
| Ashkenazi Jewish | 0.34 | 0.33 | notable |
| East Asian | 0.16 | 0.16 | notable |
| Finnish | 0.16 | 0.16 | notable |
| European (Non-Finnish) | 0.20 | 0.20 | notable |
| South Asian | 0.19 | 0.18 | notable |
| Other | 0.26 | 0.25 | notable |
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. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.168
Intolerance Scores
- LoFtool
- 0.208
- RVIS EVS
- 1.71
- RVIS percentile EVS
- 96.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.203
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |