Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

MICB

MHC class I polypeptide-related sequence B

translation score 0.58, read 2026-10-23; 2 sealed predictions, 0 held; 2 receipts.

Six readers

readerfoundscore
genetics
Open Targets		no genetic evidence; overall 0.02 from other evidence0.00
cell type
Human Protein Atlas		cell type enhanced in microglia (7 nCPM)1.00
chemistry
Open Targets		reachable by antibody0.45
trials
ClinicalTrials.gov		no Parkinson's trials on record: an open field1.00
literature
PubMed		3 Parkinson's papers of 7470.82
pathways
Reactome		1 pathway; mostly immune signalling0.90
proposal for MICB, translation score 0.58

Knock down and overexpress MICB 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 MICB 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. MICB in microglia, braak-0.09 (p 0.815) → -0.01 (p 0.982)receipt 7386
  2. MICB in dopamine neurons, braak-0.02 (p 0.962) → -0.65 (p 0.058)receipt 7387

Swarm cases

receipt 7387: MICB in dopamine neurons, braak

power
full sample -0.30 (p 0.225, n 18), 95% CI -0.67 to +0.19. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: -0.24 (p 0.346, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.37 (p 0.135, n 18). could be the mix.
skeptic
leave-one-out range -0.43 to -0.20, sign flips 0; without severely affected donors -0.30 (p 0.225, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for MICB in dopamine neurons.

case closed: nothing better to follow up.

receipt 7386: MICB in microglia, braak

power
full sample -0.07 (p 0.794, n 18), 95% CI -0.52 to +0.41. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: -0.08 (p 0.767, n 18). does not hold up.
composition
microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.06 (p 0.814, n 18). could be the mix.
skeptic
leave-one-out range -0.22 to +0.06, sign flips 4; without severely affected donors -0.07 (p 0.794, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for MICB in microglia.

case closed: nothing better to follow up.

Receipts

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