Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

B3GALT4

beta-1,3-galactosyltransferase 4

translation score 0.56, read 2026-10-21; 2 sealed predictions, 0 held; 2 receipts.

Six readers

readerfoundscore
genetics
Open Targets
no genetic evidence; overall 0.05 from other evidence0.00
cell type
Human Protein Atlas
cell type enhanced, including microglia; strongest in papillary tip epithelial cells0.75
chemistry
Open Targets
reachable by antibody0.36
trials
ClinicalTrials.gov
no Parkinson's trials on record: an open field1.00
literature
PubMed
2 Parkinson's papers of 270.85
pathways
Reactome
2 pathways; mostly lysosome and autophagy1.00
proposal for B3GALT4, translation score 0.56

Knock down and overexpress B3GALT4 in microglia; measure glucocerebrosidase (GCase) activity and LC3-II and p62 flux 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
glucocerebrosidase (GCase) activity and LC3-II and p62 flux
Functional readout
uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
Rule-out
If neither arm moves glucocerebrosidase (GCase) activity 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 B3GALT4 in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: glucocerebrosidase (GCase) activity and LC3-II and p62 flux; 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. B3GALT4 in dopamine neurons, braak-0.31 (p 0.416) → -0.53 (p 0.146)receipt 5511
  2. B3GALT4 in microglia, braak-0.33 (p 0.390) → +0.30 (p 0.435)receipt 5510

Swarm cases

receipt 5511: B3GALT4 in dopamine neurons, braak

power
full sample -0.46 (p 0.054, n 18), 95% CI -0.76 to +0.01. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: -0.45 (p 0.062, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.46 (p 0.052, n 18). could be the mix.
skeptic
leave-one-out range -0.57 to -0.38, sign flips 0; without severely affected donors -0.46 (p 0.054, n 18). robust.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for B3GALT4 in dopamine neurons.

case closed: nothing better to follow up.

receipt 5510: B3GALT4 in microglia, braak

power
full sample -0.07 (p 0.787, n 18), 95% CI -0.52 to +0.41. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: -0.03 (p 0.901, n 18). does not hold up.
composition
microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.06 (p 0.814, n 18). could be the mix.
skeptic
leave-one-out range -0.20 to +0.05, sign flips 3; 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 B3GALT4 in microglia.

case closed: nothing better to follow up.

Receipts

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