Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.87 (overall 0.54) | 0.87 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 23 Parkinson's papers of 141 | 0.58 |
| pathways Reactome | in no curated pathway | 0.00 |
Knock down and overexpress STK39 in a dopamine neuron, astrocyte and microglia tri-culture; measure a transcriptome-wide state shift (bulk RNA-seq) 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
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- dopamine neuron survival after α-synuclein fibril challenge
- Rule-out
- If neither arm moves a transcriptome-wide state shift (bulk RNA-seq) 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 STK39 in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Earlier readings: 2026-10-26 0.61; 2026-10-25 0.61; 2026-10-24 0.61; 2026-10-23 0.61.
Sealed predictions
- STK39 in dopamine neurons, braak+0.21 (p 0.586) → -0.32 (p 0.407)receipt 0600
- STK39 in dopamine neurons, braak+0.52 (p 3.6e-4) → +0.17 (p 0.286)receipt 0151
- STK39 in dopamine neurons, resilience+0.02 (p 0.938) → -0.43 (p 0.089)receipt 0152
Swarm cases
receipt 0600: STK39 in dopamine neurons, braak
- power
- full sample -0.03 (p 0.922, n 18), 95% CI -0.49 to +0.45. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.01 (p 0.956, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.03 (p 0.922, n 18). could be the mix.
- skeptic
- leave-one-out range -0.15 to +0.09, sign flips 5; without severely affected donors -0.03 (p 0.922, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for STK39 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0152: STK39 in dopamine neurons, resilience
- power
- full sample -0.25 (p 0.207, n 55), 95% CI -0.48 to +0.02. the interval is wide: not enough donors to tell.
- confounder
- adjusted for age, sex and PMI: -0.25 (p 0.199, n 55). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.12 (p 0.542); controlling for it: -0.21 (p 0.283, n 55). could be the mix.
- skeptic
- leave-one-out range -0.35 to -0.19, sign flips 0; without severely affected donors -0.18 (p 0.374, n 46). fragile.
- cell type
- no other cell group does better.
- axis
- braak beats resilience for STK39 in dopamine neurons: +0.38 (p 3.5e-4, n 84). proposing braak.
case closed: every proposal failed a challenge.
receipt 0151: STK39 in dopamine neurons, braak
- power
- full sample +0.38 (p 3.5e-4, n 84), 95% CI +0.18 to +0.55. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for age, sex and PMI: +0.36 (p 8.6e-4, n 84). holds up.
- composition
- dopamine neurons share of nuclei vs axis -0.72 (p 1.8e-14); controlling for it: +0.05 (p 0.649, n 84). could be the mix.
- skeptic
- leave-one-out range +0.36 to +0.42, sign flips 0; without severely affected donors +0.32 (p 0.0047, n 75). robust.
- cell type
- strongest in GABA neurons: -0.55 (p 5.0e-8, n 84) vs +0.38 in dopamine neurons. proposing GABA neurons.
- axis
- no measure beats "tracks Braak Lewy-body stage" for STK39 in dopamine neurons.
follow-up confirmed in ventral tegmental area.
follow-up STK39 · GABA neurons · braak: ventral tegmental area -0.50 p 2.8e-6 (needs p < 0.0021)
Receipts
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