Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

P4HB

prolyl 4-hydroxylase subunit beta

translation score 0.57, read 2026-10-22; 1 sealed predictions, 0 held; 1 receipts.

Six readers

readerfoundscore
genetics
Open Targets		no genetic evidence; overall 0.03 from other evidence0.00
cell type
Human Protein Atlas		expressed broadly, no clear home in brain cells0.40
chemistry
Open Targets		compounds already reach it: lomitapide mesylate, slx-4090, implitapide +10.90
trials
ClinicalTrials.gov		no Parkinson's trials on record: an open field1.00
literature
PubMed		1 Parkinson's papers of 4520.91
pathways
Reactome		12 pathways; mostly immune signalling0.90
proposal for P4HB, translation score 0.57

Knock down and overexpress P4HB in a dopamine neuron, astrocyte and microglia tri-culture; measure IL-1β and TNF release and surface HLA-DR and dopamine neuron survival after α-synuclein fibril challenge.

Cell type
a dopamine neuron, astrocyte and microglia tri-culture
Direction
Both arms: public data does not say which way helps; existing compounds already reach the inhibition arm.
Molecular readout
IL-1β and TNF release and surface HLA-DR
Functional readout
dopamine neuron survival after α-synuclein fibril challenge
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 P4HB in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.

Sealed predictions

  1. P4HB in dopamine neurons, braak-0.02 (p 0.964) → -0.06 (p 0.886)receipt 6693

Swarm cases

receipt 6693: P4HB in dopamine neurons, braak

power
full sample -0.03 (p 0.894, n 18), 95% CI -0.49 to +0.44. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: -0.09 (p 0.709, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.09 (p 0.709, n 18). could be the mix.
skeptic
leave-one-out range -0.15 to +0.07, sign flips 6; without severely affected donors -0.03 (p 0.894, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for P4HB in dopamine neurons.

case closed: nothing better to follow up.

Receipts

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