Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

PARL

presenilin associated rhomboid like

translation score 0.43, read 2026-10-22; 2 sealed predictions, 0 held; 3 receipts.

Six readers

readerfoundscore
genetics
Open Targets
no genetic evidence; overall 0.04 from other evidence0.00
cell type
Human Protein Atlas
cell type enhanced, including microglia; strongest in oocytes0.75
chemistry
Open Targets
a small-molecule pocket0.60
trials
ClinicalTrials.gov
no Parkinson's trials on record: an open field1.00
literature
PubMed
30 Parkinson's papers of 2800.55
pathways
Reactome
1 pathway; mostly other0.30

No case: the score is under the bar. Receipt 6262

Sealed predictions

  1. PARL in dopamine neurons, braak-0.07 (p 0.849) → +0.28 (p 0.467)receipt 6271
  2. PARL in microglia, braak+0.61 (p 0.078) → +0.27 (p 0.474)receipt 6270

Swarm cases

receipt 6271: PARL in dopamine neurons, braak

power
full sample +0.05 (p 0.854, n 18), 95% CI -0.43 to +0.50. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: +0.11 (p 0.677, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.24 (p 0.337, n 18). could be the mix.
skeptic
leave-one-out range -0.08 to +0.21, sign flips 4; without severely affected donors +0.05 (p 0.854, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for PARL in dopamine neurons.

case closed: nothing better to follow up.

receipt 6270: PARL in microglia, braak

power
full sample +0.48 (p 0.046, n 18), 95% CI +0.01 to +0.77. the interval excludes zero: something may be there, smaller than a half can see.
confounder
adjusted for sex: +0.45 (p 0.063, n 18). does not hold up.
composition
microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: +0.37 (p 0.132, n 18). could be the mix.
skeptic
leave-one-out range +0.41 to +0.65, sign flips 0; without severely affected donors +0.48 (p 0.046, n 18). robust.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for PARL in microglia.

case closed: nothing better to follow up.

Receipts

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