TPSAB1

Chr 16

tryptase alpha/beta 1

Also known as: TPS1, TPS2, TPSB1, TPSB2, Tryptase-2

NCBI Gene: 7177 ENSG00000172236 UniProt: Q15661 OMIM: 191080

Tryptase is the major neutral serine protease present in mast cells that is secreted upon mast cell activation and degranulation, playing a role in innate immunity and allergic responses. Mutations in TPSAB1 cause hereditary alpha-tryptasemia, an autosomal dominant disorder characterized by elevated baseline serum tryptase levels and symptoms including flushing, pruritus, gastrointestinal dysfunction, and connective tissue abnormalities. The gene shows very low constraint against loss-of-function variants, suggesting that complete loss of function may be tolerated.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.95

Clinical Summary— TPSAB1

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

54 VUS of 98 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — TPSAB1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.95LOEUF

pLI 0.000

Z-score -1.90

OE 1.66 (1.08–1.95)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-3.13Z-score

OE missense 1.74 (1.57–1.92)

247 obs / 142.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.66 (1.08–1.95)

0≤0.351.4

Missense OE?1.74 (1.57–1.92)

0≤0.61.4

Synonymous OE?1.69

0≤1.21.6

LoF obs/exp: 16 / 9.6Missense obs/exp: 247 / 142.1Syn Z: -4.38

This gene — mechanism propensity

0.6358th %ile

GOF

0.6149th %ile

LOF

0.3842th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

98 submitted variants in ClinVar

ClinVar

Classification Summary

VUS54

Likely Benign9

Benign34

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	54	0	0	54
Likely Benign	5	0	4	9
Benign	11	18	5	34
Total	70	18	9	97

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

48 pathogenic / likely-pathogenic (of 66) ClinVar copy-number / structural variants overlap TPSAB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →