Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

CLEC5A

C-type lectin domain containing 5A

translation score 0.56, read 2026-10-24; 2 sealed predictions, 0 held; 2 receipts.

Six readers

readerfoundscore
genetics
Open Targets		no genetic evidence; overall 0.01 from other evidence0.00
cell type
Human Protein Atlas		cell type enhanced, including microglia; strongest in neutrophil progenitors0.75
chemistry
Open Targets		reachable by antibody0.45
trials
ClinicalTrials.gov		no Parkinson's trials on record: an open field1.00
literature
PubMed		1 Parkinson's papers of 1530.91
pathways
Reactome		3 pathways; mostly immune signalling0.90
proposal for CLEC5A, translation score 0.56

Knock down and overexpress CLEC5A in microglia; measure IL-1β and TNF release and surface HLA-DR and uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release).

Cell type
microglia
Direction
Both arms: public data does not say which way helps.
Molecular readout
IL-1β and TNF release and surface HLA-DR
Functional readout
uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
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 CLEC5A in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release). Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.

Sealed predictions

  1. CLEC5A in dopamine neurons, braak+0.33 (p 0.386) → -0.16 (p 0.689)receipt 9001
  2. CLEC5A in microglia, braak-0.32 (p 0.406) → -0.70 (p 0.035)receipt 9000

Swarm cases

receipt 9001: CLEC5A in dopamine neurons, braak

power
full sample +0.11 (p 0.671, n 18), 95% CI -0.38 to +0.55. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: +0.12 (p 0.627, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.19 (p 0.444, n 18). could be the mix.
skeptic
leave-one-out range -0.02 to +0.19, sign flips 1; without severely affected donors +0.11 (p 0.671, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for CLEC5A in dopamine neurons.

case closed: nothing better to follow up.

receipt 9000: CLEC5A in microglia, braak

power
full sample -0.57 (p 0.013, n 18), 95% CI -0.82 to -0.14. the interval excludes zero: something may be there, smaller than a half can see.
confounder
adjusted for sex: -0.59 (p 0.011, n 18). holds up.
composition
microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.51 (p 0.031, n 18). not the mix.
skeptic
leave-one-out range -0.69 to -0.51, sign flips 0; without severely affected donors -0.57 (p 0.013, n 18). robust.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for CLEC5A in microglia.

case closed: nothing better to follow up.

Receipts

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