Linked hypotheses (20)

• SMN1 loss abolishes Sm ring ribonucleoprotein assembly, causing spliceosome dysfunction and motor neuron-selective mRNA processing failure that drives SMA pathology
  targetconf 98%
• SMN2 exon-7 splicing correction via ASO, small molecule, or base editing restores full-length SMN protein above therapeutic threshold, reversing motor neuron degeneration in SMA
  targetconf 95%
• SMN2 copy number determines residual full-length SMN protein output via exon 7 inclusion frequency, creating a quantitative threshold that dictates motor neuron survival and SMA disease severity
  targetconf 95%
• [Neuroprotection] NCALD is implicated in SMA pathogenesis based on 8 converging claims
  targetconf 92%
• [Gene Expression] NCALD is implicated in SMA pathogenesis based on 3 converging claims
  targetconf 92%
• [Protein Interaction] NCALD is implicated in SMA pathogenesis based on 2 converging claims
  targetconf 92%
• NCALD reduction rescues SMA phenotype by restoring endocytic flux and neuronal maturation in motor neurons
  targetconf 92%
• [Biomarker] NCALD is implicated in SMA pathogenesis based on 3 converging claims
  targetconf 91%
• NCALD is a convergent node in SMA pathogenesis based on 6 claims from 3 independent sources (drug_target, gene_expression, neuroprotection, other).
  mechanismconf 91%
• [Drug Target] NCALD is implicated in SMA pathogenesis based on 2 converging claims
  targetconf 90%
• [Drug Efficacy] NCALD is implicated in SMA pathogenesis based on 9 converging claims
  targetconf 89%
• NCALD reduction represents an SMN-independent therapeutic target that ameliorates SMA phenotypes through calcium signaling modulation.
  targetconf 89%
• MuSK_chembl_1 × NCALD affinity via computational screening (Boltz-2)
  mechanismconf 89%
• MuSK_chembl_1 binds NCALD (Boltz-2 iPTM=0.894)
  targetconf 89%
• fasudil binds NCALD (Boltz-2 iPTM=0.893)
  targetconf 89%
• LIMK_chembl_1 binds NCALD (Boltz-2 iPTM=0.888)
  targetconf 89%
• NCALD × PAK1 interaction (auto-validated BOLTZ2_PPI iPTM=0.89)
  mechanismconf 89%
• [Safety] NCALD is implicated in SMA pathogenesis based on 2 converging claims
  targetconf 88%
• NCALD reduction rescues SMA pathology through modulation of calcium signaling in motor neurons
  targetconf 88%
• NCALD reduction synergizes with SMN restoration to provide superior therapeutic benefit in SMA through dual modulation of calcium signaling and neuromuscular junction function.
  targetconf 88%

Top compound hits (10)

Linked claims (50)