TPSAB1

Chr 16

tryptase alpha/beta 1

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

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.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.95
Clinical SummaryTPSAB1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — TPSAB1
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.95LOEUF
pLI 0.000
Z-score -1.90
OE 1.66 (1.081.95)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-3.13Z-score
OE missense 1.74 (1.571.92)
247 obs / 142.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.66 (1.081.95)
00.351.4
Missense OE1.74 (1.571.92)
00.61.4
Synonymous OE1.69
01.21.6
LoF obs/exp: 16 / 9.6Missense obs/exp: 247 / 142.1Syn Z: -4.38
DN
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TPSAB1 · 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