Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

TBXAS1

thromboxane A synthase 1

translation score 0.66, read 2026-10-18; 2 sealed predictions, 0 held; 2 receipts.

Six readers

readerfoundscore
genetics
Open Targets		genetic association 0.39 (overall 0.24)0.39
cell type
Human Protein Atlas		cell type enhanced, including microglia; strongest in neutrophils0.75
chemistry
Open Targets		compounds already reach it: ozagrel, picotamide, terbogrel1.00
trials
ClinicalTrials.gov		no Parkinson's trials on record: an open field1.00
literature
PubMed		2 Parkinson's papers of 1170.85
pathways
Reactome		3 pathways; mostly other0.30
proposal for TBXAS1, translation score 0.66

Knock down and overexpress TBXAS1 in microglia; measure a transcriptome-wide state shift (bulk RNA-seq) and uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release).

Cell type
microglia
Direction
Both arms: public data does not say which way helps; existing compounds already reach the inhibition arm.
Molecular readout
a transcriptome-wide state shift (bulk RNA-seq)
Functional readout
uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
Rule-out
If neither arm moves a transcriptome-wide state shift (bulk RNA-seq) by 20% or more against non-targeting and empty-vector controls, across three independent differentiations, the hypothesis is wrong.
Lab request
CRISPRi knockdown and lentiviral overexpression of TBXAS1 in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release). Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.

Sealed predictions

  1. TBXAS1 in dopamine neurons, braak-0.35 (p 0.349) → +0.27 (p 0.484)receipt 1787
  2. TBXAS1 in microglia, braak-0.38 (p 0.311) → +0.83 (p 0.006)receipt 1786

Swarm cases

receipt 1787: TBXAS1 in dopamine neurons, braak

power
full sample +0.04 (p 0.888, n 18), 95% CI -0.44 to +0.49. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: +0.01 (p 0.983, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.08 (p 0.754, n 18). could be the mix.
skeptic
leave-one-out range -0.08 to +0.16, sign flips 5; without severely affected donors +0.04 (p 0.888, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for TBXAS1 in dopamine neurons.

case closed: nothing better to follow up.

receipt 1786: TBXAS1 in microglia, braak

power
full sample +0.23 (p 0.351, n 18), 95% CI -0.26 to +0.63. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: +0.22 (p 0.374, n 18). does not hold up.
composition
microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: +0.20 (p 0.429, n 18). could be the mix.
skeptic
leave-one-out range +0.15 to +0.39, sign flips 0; without severely affected donors +0.23 (p 0.351, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for TBXAS1 in microglia.

case closed: nothing better to follow up.

Receipts

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