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%
• SMN1 loss-of-function depletes functional SMN protein below a critical threshold, impairing snRNP biogenesis and splicing homeostasis in motor neurons, driving selective neurodegeneration in SMA
  targetconf 98%
• AAV9-mediated SMN1 gene replacement restores functional SMN protein complex assembly in motor neurons, rescuing snRNP biogenesis and splicing fidelity to prevent neurodegeneration in SMA
  targetconf 97%
• Correcting SMN2 exon 7 splicing via ISS-N1 blockade or small-molecule RNAP modulation restores functional SMN protein and rescues motor neuron survival in SMA
  targetconf 97%
• Restoration of SMN protein complex function rescues snRNP biogenesis and pre-mRNA splicing fidelity in motor neurons, reversing the core molecular pathology of SMA
  targetconf 97%
• SMN1 loss-of-function depletes functional SMN protein, disrupting snRNP biogenesis and axonal mRNA trafficking to drive anterior horn cell degeneration in SMA
  targetconf 97%
• SMN2 exon 7 splicing correction via small molecules or antisense oligonucleotides restores functional SMN protein above the pathological threshold, rescuing motor neuron survival in SMA
  targetconf 97%
• Y27632 × SMN1_YGbox affinity via computational screening (Boltz-2)
  mechanismconf 96%
• Y27632 binds SMN1_YGbox (Boltz-2 iPTM=0.964)
  targetconf 96%
• DEPTOR × SMN1 interaction (auto-validated BOLTZ2_PPI iPTM=0.96)
  mechanismconf 96%
• HIF1A × SMN1 interaction (auto-validated BOLTZ2_PPI iPTM=0.96)
  mechanismconf 96%
• SMN1 loss-of-function depletes functional SMN protein below the threshold required for spliceosomal snRNP assembly, causing selective motor neuron degeneration that can be rescued by restoring SMN levels via gene replacement, splice-switching, or combinatorial approaches
  targetconf 95%
• [Gene Expression] SMN1 is implicated in SMA pathogenesis based on 224 converging claims
  targetconf 95%
• SMN1 loss depletes functional SMN protein at motor neuron axons and neuromuscular junctions, causing SMA through impaired snRNP biogenesis and local mRNA translation, rescuable by SMN restoration via AAV9-mediated gene replacement or splice-switching ASOs
  targetconf 95%
• 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 exon 7 splicing correction via antisense oligonucleotide-mediated ISS-N1 blockade restores sufficient full-length SMN protein to prevent motor neuron degeneration in a copy-number-dependent manner
  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%
• SMN protein complex restoration via splicing modulation, ASO-mediated exon inclusion, or AAV9-mediated gene replacement rescues snRNP biogenesis and pre-mRNA splicing fidelity to halt SMA motor neuron degeneration
  targetconf 95%
• SMN complex insufficiency impairs Sm ring assembly onto pre-snRNAs, causing spliceosomal snRNP deficiency that selectively disrupts motor neuron transcriptome integrity and drives SMA neurodegeneration
  targetconf 95%
• SMN1 × TP53 interaction (auto-validated BOLTZ2_PPI iPTM=0.95)
  mechanismconf 95%

Top compound hits (10)

Linked claims (23)