TARGETproteinHomo sapiens
SMN_PROTEIN — SMN Protein Complex
Description
Essential for snRNP biogenesis and pre-mRNA splicing. Loss of full-length SMN protein causes SMA.
Linked hypotheses (20)
- SMN1 loss abolishes Sm ring ribonucleoprotein assembly, causing spliceosome dysfunction and motor neuron-selective mRNA processing failure that drives SMA pathologytargetconf 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 SMAtargetconf 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 SMAtargetconf 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 SMAtargetconf 97%
- Restoration of SMN protein complex function rescues snRNP biogenesis and pre-mRNA splicing fidelity in motor neurons, reversing the core molecular pathology of SMAtargetconf 97%
- SMN1 loss-of-function depletes functional SMN protein, disrupting snRNP biogenesis and axonal mRNA trafficking to drive anterior horn cell degeneration in SMAtargetconf 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 SMAtargetconf 97%
- 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 approachestargetconf 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 ASOstargetconf 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 SMAtargetconf 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 mannertargetconf 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 severitytargetconf 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 degenerationtargetconf 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 neurodegenerationtargetconf 95%
- [Motor Function] SMN_PROTEIN is implicated in SMA pathogenesis based on 91 converging claimstargetconf 93%
- [Gene Expression] SMN_PROTEIN is implicated in SMA pathogenesis based on 75 converging claimstargetconf 93%
- [Survival] SMN_PROTEIN is implicated in SMA pathogenesis based on 19 converging claimstargetconf 93%
- [Biomarker] SMN_PROTEIN is implicated in SMA pathogenesis based on 83 converging claimstargetconf 92%
- [Protein Interaction] SMN_PROTEIN is implicated in SMA pathogenesis based on 86 converging claimstargetconf 92%
- SMN1 loss drives progressive spinal motor neuron degeneration through convergent failure of spliceosomal snRNP assembly, axonal mRNA transport, and mitochondrial homeostasis, all rescuable by SMN protein restoration or downstream neuroprotective pathway augmentationtargetconf 92%
Top compound hits (10)
| Compound ID | SMILES | Score | Tier |
|---|---|---|---|
| CHEMBL1450813 | COc1cc(/C=C2\N=C3CCCCCN3C2=O)ccc1O | 0.958 | promising |
| CHEMBL1528143 | COc1ccccc1CNC(=O)COc1ccc2c(c1)CCC2 | 0.871 | promising |
| CHEMBL1537645 | COc1cc(NC(=O)Cc2ccc(F)cc2)cc(OC)c1OC | 0.869 | promising |
| CHEMBL1411446 | O=C(CCC1COc2ccccc2O1)NCc1ccccc1 | 0.862 | promising |
| CHEMBL1538688 | CC(=O)c1ccc(Oc2cc(C(F)(F)F)cnc2C(N)=O)cc1 | 0.857 | promising |
| CHEMBL1595318 | CC(C)(C)NC(=O)C(c1ccccc1)N(C(=O)c1ccco1)C1CC1 | 0.853 | promising |
| CHEMBL1328308 | CCOC(=O)Nc1ccc(S(=O)(=O)NC(C)=O)cc1 | 0.850 | promising |
| CHEMBL1490089 | CC(SCc1ccccc1)C(=O)NC1CCCC1 | 0.849 | promising |
| CHEMBL1420277 | COc1ccc(N2C(=O)C(O)C2c2ccc(C)cc2)cc1 | 0.837 | promising |
| CHEMBL3191620 | COc1cc(/C=N/S(=O)(=O)CCc2ccccc2)ccc1O | 0.834 | promising |
Linked claims (50)
| Type | Predicate | Conf | Source |
|---|---|---|---|
| motor function | Myomixer combined with antisense oligonucleotide SMN therapy enhances motor function with 82% decrease in righting time in SMA mice. | 69% | 34115448 |
| neuroprotection | Exercise-induced neuroprotection in SMA-like mice is independent of SMN protein expression levels. | 65% | 26915343 |
| motor function | Olesoxime treatment was associated with changes from baseline in Motor Function Measure (MFM) Dimension 1 (D1) + Dimension 2 (D2) Score in patients with SMA (clinical trial result) | 65% | NCT02628743_results |
| gene expression | SMN expression increases Bcl-xL protein levels by approximately 2.5-fold in brains of transgenic mice over-expressing SMN. | 65% | 22732506 |
| neuroprotection | SMN-induced apoptosis can be partially reversed by expression of an SMN rescue construct. | 65% | 17976539 |
| protein interaction | The SMN complex can interact with the zinc finger protein ZPR1. | 65% | 15767679 |
| protein interaction | WRAP53 protein directs the SMN complex to Cajal bodies through direct protein-protein interactions. | 65% | 21072240 |
| pathway membership | SMN-deficiency does not prevent activation of stress-induced JNK-c-Jun signaling pathway, as demonstrated by anisomycin treatment and sciatic nerve ligation. | 65% | 31272106 |
| protein interaction | ZPR1 is a zinc finger protein that interacts with complexes formed by SMN. | 65% | 16648254 |
| gene expression | Loganin upregulates SMN expression in gastrocnemius muscle of SMAΔ7 mice. | 65% | 27241020 |
| biomarker | SMN protein and SMN mRNA were measured as biomarkers in SMA Type II and III patients treated with Hydroxyurea (clinical trial result) | 65% | NCT00568802_results |
| biomarker | SMN protein is a biomarker for Spinal Muscular Atrophy (clinical trial result) | 65% | NCT00568698_results |
| drug efficacy | Increasing SMN with therapeutic antisense oligonucleotide improves cardiac pathology in severe SMA mice. | 65% | 29220503 |
| gene expression | Smn restoration normalizes expression of P53-associated transcripts in SMA motor units. | 65% | 35551393 |
| neuroprotection | The transcription factor NRF2 is implicated in ceftriaxone-mediated neuroprotection in SMA. | 65% | 21295027 |
| gene expression | Restoring SMN levels only partially restores myomaker and myomixer expression. | 65% | 34115448 |
| biomarker | SMN protein is an appropriate biomarker for monitoring and evaluating the efficacy of risdiplam treatment in SMA. | 65% | 40795449 |
| protein interaction | FGF-2(23) forms a complex with small nuclear RNAs U2 and U4 as a functional consequence of binding to SMN. | 65% | 15222879 |
| gene expression | SMN deficiency reduces GAP43 mRNA and protein levels in axons and growth cones of motor neurons. | 65% | 27030765 |
| motor function | SMN-targeted therapies increase the production of SMN protein in motor neurons and improve motor function and survival. | 65% | 32392694 |
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