Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

MT-ATP6

mitochondrially encoded ATP synthase membrane subunit 6

translation score 0.68, read 2026-10-17; 1 sealed predictions, 0 held; 1 receipts.

Six readers

readerfoundscore
genetics
Open Targets		genetic association 0.55 (overall 0.34)0.55
cell type
Human Protein Atlas		expressed broadly, no clear home in brain cells0.40
chemistry
Open Targets		a small-molecule pocket0.60
trials
ClinicalTrials.gov		no Parkinson's trials on record: an open field1.00
literature
PubMed		5 Parkinson's papers of 2690.76
pathways
Reactome		4 pathways; mostly mitochondrial quality control1.00
proposal for MT-ATP6, translation score 0.68

Knock down and overexpress MT-ATP6 in a dopamine neuron, astrocyte and microglia tri-culture; measure PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub) 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.
Molecular readout
PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub)
Functional readout
dopamine neuron survival after α-synuclein fibril challenge
Rule-out
If neither arm moves PINK1–parkin mitophagy flux (mt-Keima) 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 MT-ATP6 in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub); 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. MT-ATP6 in dopamine neurons, braak+0.04 (p 0.912) → +0.08 (p 0.838)receipt 0966

Swarm cases

receipt 0966: MT-ATP6 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: +0.07 (p 0.774, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.11 (p 0.677, n 18). could be the mix.
skeptic
leave-one-out range -0.07 to +0.15, sign flips 4; 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 MT-ATP6 in dopamine neurons.

case closed: nothing better to follow up.

Receipts

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