Familial TAAD (ACTA2) OMIM 611788

In Familial TAAD (ACTA2, OMIM 611788), the master switch sits on the ↑ UP branch ([F] forced below); the healthy state is the OFF well. The forced corrective direction is to lower s toward OFF branch (polarity: clear). Classification: ✓ Recovers an existing standard. Direction only — no dose, no efficacy magnitude.

The disease maps to an R19 double-well whose corrective lever is read straight off the cusp (barrier 0.4612, γ 1.3583, spinodal 0.6093). The corrective direction is forced [F]; the agent names below are direction-concordant labels at grade [O] (no dose, no efficacy or safety magnitude). This is a research hypothesis offered to experts, not medical advice.

The emergence switch

The switch for Familial TAAD is an R19 double-well emerged from the real proximal-promoter DNA of ACTA2. Its geometry is fixed by measured stiffness γ (never fitted); the numbers below are read directly off that cusp.

emergent axis: ↑ UP [F]
healthy branch: OFF
lesion: GOF
γ (stiffness): 1.3583
barrier: 0.4612
spinodal: 0.6093
s_on / s_off: 1.1655 / -1.1655
fragility: 0.64
corrective polarity: clear
forced direction: lower s toward OFF branch

Chemistry feasibility (DIRECTION only [O]). small-molecule recrossing of the fold is geometrically plausible (barrier 0.4612 at neutral drive; lower barrier = smaller drive to supply). [O] -- no affinity/potency/dose/efficacy asserted.

The derived corrective lever

The cusp forces a corrective direction: lower s toward OFF branch. This is the load-bearing output of the framework — it is [F] forced, and it is falsifiable. 2 lever families are derived; the lead is h-restore (drive modulator).

h-restore (drive modulator)sign: decreasegeometric rank 0.64

Mechanism. remove / oppose the drive (clear the accumulating load that pins the disease branch)

Applies to. allele-agnostic (downstream/environmental tilt)

favoured when the switch is fragile -- a small drive shift recrosses the fold

Falsifier. If clearing/opposing the accumulating aortic-wall haemodynamic shear stress and TGF-beta-driven medial degeneration on the ACTA2 smooth-muscle actin defect does NOT relieve the disease branch in a ACTA2 model, the h-restore(clear) lever is refuted for this axis.

gamma-restore (stabiliser / chaperone)sign: Nonegeometric rank 0.00

Mechanism. N/A

Applies to. none (honest exclusion)

EXCLUDED: gain-of-function -- the lesion is not a destabilised healthy product to stiffen; the corrective move is to clear/oppose the toxic drive (h-restore)

Falsifier. If a folding-stabiliser/chaperone does NOT re-deepen the healthy well for a residual ACTA2 allele (no rescue that a null allele lacks), the gamma-restore lever is refuted; null alleles are excluded by construction.

Agents mapped onto the lever

✓ Agreement with established practice. The corrective direction derived here (lower s toward OFF branch) independently matches an agent already in clinical use for this disease: aortic-wall-stress reduction (beta-adrenergic antagonism with angiotensin-receptor blockade) lowering haemodynamic and TGF-beta drive. The geometry recovered known medicine — this is a validation signal for the logic, not a new treatment claim by this kit.

Existing agents whose known action is direction-concordant with the derived lever (status as pinned in the corpus; no dose, no efficacy magnitude).
agent (class)	dir.	status	phase	map
aortic-wall-stress reduction (beta-adrenergic antagonism with angiotensin-receptor blockade) lowering haemodynamic and TGF-beta drive Guo 2007 Nat Genet 39:1488; Milewicz 2008 Annu Rev Genomics Hum Genet 9:283	decrease	established standard of care	0	✓ in use

⚠ Mechanism-direction only — do not self-administer; no dose (unvalidated; set by a physician / national authority); not an approved use.

Evidence & provenance

What is reproduced vs. cited for this page.
element	grade	basis
R19 switch & cusp geometry (this page)	[V] verified	emerged from measured promoter γ of `ACTA2`; deterministic, 2×sha256 identical
corrective direction	[F] forced	forced by the cusp sign; falsifiable (see lever falsifiers)
mapped agents / leads	[O] open	direction-concordance only; corpus-pinned (2026-06-21); no dose, no efficacy/safety magnitude

Reading the agent column. VALIDATION SIGNAL -- the agent is already approved / established standard for this disease, so the direction logic recovered known clinical practice. Not a new claim by this kit. GENUINE HYPOTHESIS -- no approved indication for this disease; the direction match is a direction-only, untested [O] lead. Basis field grades the evidence (investigational here / in a related condition / off-label / speculative).