Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

DNAJC6

DnaJ heat shock protein family (Hsp40) member C6

translation score 0.74, read 2026-10-27; 4 sealed predictions, 0 held; 4 receipts.

Six readers

readerfoundscore
genetics
Open Targets		genetic association 0.83 (overall 0.82)0.83
cell type
Human Protein Atlas		cell type enhanced in oligodendrocytes (1220 nCPM)1.00
chemistry
Open Targets		hard to drug0.27
trials
ClinicalTrials.gov		no Parkinson's trials on record: an open field1.00
literature
PubMed		83 Parkinson's papers of 1330.42
pathways
Reactome		3 pathways; mostly vesicle traffic1.00
proposal for DNAJC6, translation score 0.74

Knock down and overexpress DNAJC6 in oligodendrocytes; measure LRRK2 kinase activity (pT73-Rab10) and lysosome position and α-synuclein uptake and myelin basic protein output under oxidative stress.

Cell type
oligodendrocytes
Direction
Both arms: public data does not say which way helps.
Molecular readout
LRRK2 kinase activity (pT73-Rab10) and lysosome position
Functional readout
α-synuclein uptake and myelin basic protein output under oxidative stress
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 DNAJC6 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: LRRK2 kinase activity (pT73-Rab10) and lysosome position; α-synuclein uptake and myelin basic protein output under oxidative stress. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.

Earlier readings: 2026-10-26 0.74; 2026-10-25 0.74; 2026-10-24 0.74; 2026-10-23 0.74.

Sealed predictions

  1. DNAJC6 in oligodendrocytes, braak+0.16 (p 0.680) → +0.25 (p 0.514)receipt 0516
  2. DNAJC6 in dopamine neurons, braak-0.40 (p 0.292) → +0.26 (p 0.498)receipt 0517
  3. DNAJC6 in oligodendrocytes, resilience+0.67 (p 0.038) → +0.18 (p 0.477)receipt 0018
  4. DNAJC6 in oligodendrocytes, braak+0.22 (p 0.155) → +0.63 (p 9.2e-6)receipt 0017

In the sealed studies

Swarm cases

receipt 0517: DNAJC6 in dopamine neurons, braak

power
full sample +0.03 (p 0.894, n 18), 95% CI -0.44 to +0.49. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: +0.03 (p 0.894, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.12 (p 0.627, n 18). could be the mix.
skeptic
leave-one-out range -0.09 to +0.12, sign flips 4; without severely affected donors +0.03 (p 0.894, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for DNAJC6 in dopamine neurons.

case closed: nothing better to follow up.

receipt 0516: DNAJC6 in oligodendrocytes, braak

power
full sample +0.18 (p 0.471, n 18), 95% CI -0.31 to +0.60. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: +0.23 (p 0.351, n 18). does not hold up.
composition
oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.23 (p 0.351, n 18). could be the mix.
skeptic
leave-one-out range +0.07 to +0.30, sign flips 0; without severely affected donors +0.18 (p 0.471, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for DNAJC6 in oligodendrocytes.

case closed: nothing better to follow up.

receipt 0018: DNAJC6 in oligodendrocytes, resilience

power
full sample +0.29 (p 0.147, n 55), 95% CI +0.02 to +0.51. the interval excludes zero: something may be there, smaller than a half can see.
confounder
adjusted for age, sex and PMI: +0.31 (p 0.119, n 55). does not hold up.
composition
oligodendrocytes share of nuclei vs axis -0.52 (p 0.0075); controlling for it: +0.27 (p 0.165, n 55). could be the mix.
skeptic
leave-one-out range +0.21 to +0.38, sign flips 0; without severely affected donors +0.37 (p 0.066, n 46). robust.
cell type
no other cell group does better.
axis
braak beats resilience for DNAJC6 in oligodendrocytes: +0.46 (p 1.1e-5, n 84). proposing braak.

follow-up confirmed in ventral tegmental area.
follow-up DNAJC6 · oligodendrocytes · braak: ventral tegmental area +0.37 p 8.1e-4 (needs p < 0.017)

receipt 0017: DNAJC6 in oligodendrocytes, braak

power
full sample +0.46 (p 1.1e-5, n 84), 95% CI +0.27 to +0.61. the interval excludes zero: something may be there, smaller than a half can see.
confounder
adjusted for age, sex and PMI: +0.40 (p 1.4e-4, n 84). holds up.
composition
oligodendrocytes share of nuclei vs axis +0.09 (p 0.422); controlling for it: +0.41 (p 1.2e-4, n 84). not the mix.
skeptic
leave-one-out range +0.44 to +0.49, sign flips 0; without severely affected donors +0.41 (p 2.9e-4, n 75). robust.
cell type
no other cell group does better.
axis
nigra beats braak for DNAJC6 in oligodendrocytes: +0.45 (p 2.0e-5, n 84). proposing nigra.

follow-up confirmed in ventral tegmental area.
follow-up DNAJC6 · oligodendrocytes · nigra: ventral tegmental area +0.34 p 0.0019 (needs p < 0.025)

Receipts

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