TPSB2

Chr 16

tryptase beta 2

Also known as: TPS2, tryptaseB, tryptaseC

Tryptase beta-2 is a serine protease that serves as the major neutral protease in mast cells and is secreted during mast cell degranulation, potentially playing a role in innate immunity. This gene is extremely tolerant to loss-of-function variants (LOEUF 1.898), and mutations in TPSB2 are associated with hereditary alpha tryptasemia, an autosomal dominant condition characterized by elevated baseline serum tryptase levels and symptoms including flushing, pruritus, gastrointestinal issues, and allergic-type reactions. The condition typically manifests with systemic symptoms affecting multiple organ systems including skin, gastrointestinal tract, and cardiovascular system.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.90
Clinical SummaryTPSB2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.90LOEUF
pLI 0.000
Z-score -0.96
OE 1.36 (0.841.90)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.04Z-score
OE missense 1.59 (1.391.82)
149 obs / 93.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.36 (0.841.90)
00.351.4
Missense OE1.59 (1.391.82)
00.61.4
Synonymous OE1.60
01.21.6
LoF obs/exp: 11 / 8.1Missense obs/exp: 149 / 93.5Syn Z: -3.10
DN
0.6841th %ile
GOF
0.72top 25%
LOF
0.3162th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TPSB2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC