Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.88 (overall 0.54) | 0.88 |
| cell type Human Protein Atlas | cell type enhanced in brain excitatory neurons (550 nCPM) | 1.00 |
| chemistry Open Targets | reachable by antibody | 0.45 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 19 Parkinson's papers of 94 | 0.61 |
| pathways Reactome | 10 pathways; mostly vesicle traffic | 1.00 |
Knock down and overexpress SH3GL2 in dopamine neurons; measure LRRK2 kinase activity (pT73-Rab10) and lysosome position and survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils.
- Cell type
- dopamine neurons
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- LRRK2 kinase activity (pT73-Rab10) and lysosome position
- Functional readout
- survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils
- Rule-out
- If neither arm moves LRRK2 kinase activity (pT73-Rab10) 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 SH3GL2 in iPSC-derived midbrain dopamine neurons (FOXA2+, LMX1A+, TH+); n = 3 differentiations; readouts: LRRK2 kinase activity (pT73-Rab10) and lysosome position; survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Earlier readings: 2026-10-26 0.82; 2026-10-25 0.82; 2026-10-24 0.82; 2026-10-23 0.82.
Sealed predictions
- SH3GL2 in dopamine neurons, braak+0.29 (p 0.442) → -0.22 (p 0.565)receipt 0601
- SH3GL2 in dopamine neurons, resiliencen/a → n/afailed
- SH3GL2 in dopamine neurons, braakn/a → n/afailed
In the sealed studies
- The synaptic vesicle cycle in resilient donors: did not hold
Swarm cases
receipt 0601: SH3GL2 in dopamine neurons, braak
- power
- full sample +0.04 (p 0.874, n 18), 95% CI -0.43 to +0.50. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.02 (p 0.942, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.00 (p 0.990, n 18). could be the mix.
- skeptic
- leave-one-out range -0.07 to +0.19, sign flips 4; without severely affected donors +0.04 (p 0.874, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SH3GL2 in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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