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Analysismoderate confidence 3 of 5: One strong study, or several smaller consistent ones.

CSPG4/NG2 is 0.0 nTPM in normal bone marrow, so the ratio metric is undefined for it - and that zero is the favourable half of its profile, which a ratio-ranked table hides entirely

also called CSPG4 marrow 0.0 · NG2 normal tissue profile · an undefined ratio is a result, not a gap

NG2 is the surface marker this project calls its clearest example of the leukaemia switching on a gene the body uses elsewhere. It is undetectable in normal bone marrow, which is good news the usual scoring method cannot express.

The same thing, for a scientist

`hyp-no-surface-antigen-is-both-fusion-driven-and-normal-tissue-clean-in-kmt2a-aff1` calls **NG2/CSPG4** its **clearest case** - a direct MLL-AF4 target gene that is also a pericyte and oligodendrocyte-precursor antigen. On the standard metric it returns **no number at all**. **CSPG4: bone marrow 0.0 nTPM. The highest-tissue/marrow ratio is therefore UNDEFINED**, the same failure the `ALB` control produces (marrow 0.0, liver 198,523.8) [E1]. This was pre-registered as condition **S3(a)** - *a near-zero denominator is not a safety number* - and it fired. 🔵 **But the raw values are the result, and they point the opposite way to a bad ratio.** Zero expression in normal marrow is **the favourable half of a surface target's profile**: the antigen is absent from the compartment being treated, so on-target marrow toxicity should be minimal. The liability is elsewhere - **lung 18.1, heart muscle 13.9, cerebral cortex 8.6, ovary 7.8**. 🟠 **The methodological point is the transferable one.** A table ranked by ratio shows CSPG4 as a blank and ranks it nowhere, when it has the most informative profile in the run: **absent where you are dosing, present in four organs you are not.** A ratio collapses two numbers into one and loses exactly the distinction a clinician needs.

Facts and figures
scriptanalyses/hpa-normal-tissue-surface-antigens/run.py
statusrun
run date2026-09-24
geneCSPG4
ensemblENSG00000173546
ensembl ID sourceHPA-sourced (not independently verified)
bone marrow ntpm0
ratio undefined reasonbone marrow 0.0 nTPM; pre-registered condition S3(a) fired
top tissues
kidney5.700kidney: 5.7ovary7.800ovary: 7.8cerebral cortex8.600cerebral cortex: 8.6heart muscle13.9heart muscle: 13.9lung18.1lung: 18.1
top tissues — the numbers behind the chart
{
  "lung": 18.1,
  "heart muscle": 13.9,
  "cerebral cortex": 8.6,
  "ovary": 7.8,
  "kidney": 5.7
}
measurements
[
  {
    "quantity": "bone marrow expression, HPA consensus RNA",
    "value": 0,
    "unit": "nTPM",
    "subject": "CSPG4/NG2 (ENSG00000173546) in normal bone marrow",
    "universe": "a 16-tissue HPA consensus panel; the highest-tissue/marrow ratio is undefined for this gene and the raw values are reported instead"
  }
]
How this could bite us back
  • Off-marrow parenchymal exposure - CSPG4 is undetectable in normal marrow, which is favourable, but reaches lung 18.1, heart muscle 13.9 and cerebral cortex 8.6 nTPM. An NG2-directed agent's risk is cardiopulmonary and neural rather than haematological - the opposite profile to a marrow antigen, needing different monitoring. mRNA is not protein.
Still open
  1. Is CSPG4 truly absent from normal marrow, or below the resolution of a whole-tissue consensus value? A single-cell marrow reference would settle it.
  2. Rank the surface antigens by the raw pair (marrow value, worst parenchymal value) rather than by their ratio. CSPG4 shows the ratio loses the distinction that matters.
Every source behind this entry (1)
  1. E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.

    In Human Protein Atlas consensus tissue RNA, CSPG4 is 0.0 nTPM in bone marrow, making the highest-tissue-over-marrow ratio undefined, while it reaches lung 18.1, heart muscle 13.9, cerebral cortex 8.6 and ovary 7.8 nTPM.

    What this evidence cannot show

    Run 2026-09-24 (cycle 136) on the same 16-tissue panel, metric and identifier guard as analyses/hpa-normal-tissue-target-filter, whose two controls reproduced (ACTB 1.21 vs 1.2; ALB undefined in both). The Ensembl id was taken from HPA's own exact-symbol row and is HPA-sourced rather than independently verified. HPA consensus values are ADULT tissue and this is an infant disease. mRNA is not protein and expression is not dependence.

    Evidence that argues against this (1)
    • A consensus value of 0.0 nTPM is a rounded aggregate, not a proof of absence. Low-level expression below the reporting threshold, or expression in a marrow subpopulation too rare to move the whole-tissue mean, would both read as 0.0. So 'absent from normal marrow' is a statement about this metric's resolution, and a single-cell marrow reference would test it properly.
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