Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

TAP2

transporter 2, ATP binding cassette subfamily B member

translation score 0.57, read 2026-10-23; 2 sealed predictions, 0 held; 2 receipts.

Six readers

readerfoundscore
genetics
Open Targets		no genetic evidence; overall 0.02 from other evidence0.00
cell type
Human Protein Atlas		cell type enhanced in microglia (19 nCPM)1.00
chemistry
Open Targets		reachable by antibody0.36
trials
ClinicalTrials.gov		1 Parkinson's trial, 0 stopped1.00
literature
PubMed		3 Parkinson's papers of 8510.82
pathways
Reactome		2 pathways; mostly immune signalling0.90
proposal for TAP2, translation score 0.57

Knock down and overexpress TAP2 in microglia; measure IL-1β and TNF release and surface HLA-DR 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.
Molecular readout
IL-1β and TNF release and surface HLA-DR
Functional readout
uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
Rule-out
If neither arm moves IL-1β 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 TAP2 in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; 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. TAP2 in dopamine neurons, braak+0.16 (p 0.685) → +0.11 (p 0.775)receipt 7873
  2. TAP2 in microglia, braak-0.29 (p 0.445) → -0.32 (p 0.400)receipt 7872

Swarm cases

receipt 7873: TAP2 in dopamine neurons, braak

power
full sample +0.07 (p 0.787, n 18), 95% CI -0.41 to +0.52. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: +0.09 (p 0.735, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.06 (p 0.807, n 18). could be the mix.
skeptic
leave-one-out range -0.04 to +0.20, sign flips 2; without severely affected donors +0.07 (p 0.787, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for TAP2 in dopamine neurons.

case closed: nothing better to follow up.

receipt 7872: TAP2 in microglia, braak

power
full sample -0.38 (p 0.123, n 18), 95% CI -0.72 to +0.11. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: -0.43 (p 0.074, n 18). does not hold up.
composition
microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.33 (p 0.182, n 18). could be the mix.
skeptic
leave-one-out range -0.53 to -0.27, sign flips 0; without severely affected donors -0.38 (p 0.123, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for TAP2 in microglia.

case closed: nothing better to follow up.

Receipts

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