SMN2

Summary

SMN2 (survival of motor neuron 2, centromeric, HGNC:11118) is a protein-coding gene on chromosome 5q13.2, encoding Survival motor neuron protein (Q16637). The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs.

This gene is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. The telomeric and centromeric copies of this gene are nearly identical and encode the same protein. While mutations in the telomeric copy are associated with spinal muscular atrophy, mutations in this gene, the centromeric copy, do not lead to disease. This gene may be a modifier of disease caused by mutation in the telomeric copy. The critical sequence difference between the two genes is a single nucleotide in exon 7, which is thought to be an exon splice enhancer. Note that the nine exons of both the telomeric and centromeric copies are designated historically as exon 1, 2a, 2b, and 3-8. It is thought that gene conversion events may involve the two genes, leading to varying copy numbers of each gene. The full length protein encoded by this gene localizes to both the cytoplasm and the nucleus. Within the nucleus, the protein localizes to subnuclear bodies called gems which are found near coiled bodies containing high concentrations of small ribonucleoproteins (snRNPs). This protein forms heteromeric complexes with proteins such as SIP1 and GEMIN4, and also interacts with several proteins known to be involved in the biogenesis of snRNPs, such as hnRNP U protein and the small nucleolar RNA binding protein. Four transcript variants encoding distinct isoforms have been described.

Source: NCBI Gene 6607 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinal muscular atrophy, type III (Moderate, GenCC)
• Clinical variants (ClinVar): 10 total
• Phenotypes (HPO): 23
• Druggable target: yes — 352 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_017411

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11118
Approved symbol	SMN2
Name	survival of motor neuron 2, centromeric
Location	5q13.2
Locus type	gene with protein product
Status	Approved
Aliases	BCD541, SMNC, GEMIN1, TDRD16B
Ensembl gene	ENSG00000205571
Ensembl biotype	protein_coding
OMIM	601627
Entrez	6607

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 10 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay

ENST00000380741, ENST00000380742, ENST00000380743, ENST00000503678, ENST00000505346, ENST00000506734, ENST00000507458, ENST00000508258, ENST00000509805, ENST00000511812, ENST00000511873, ENST00000514914, ENST00000614240, ENST00000626847, ENST00000628696, ENST00000940688, ENST00000940689, ENST00000940690

RefSeq mRNA: 4 — MANE Select: NM_017411 NM_017411, NM_022875, NM_022876, NM_022877

CCDS: CCDS4007, CCDS4008, CCDS54867

Canonical transcript exons

ENST00000380743 — 9 exons

Exon	Start	End
ENSE00001725187	70063415	70063486
ENSE00001904512	70049669	70049766
ENSE00003550962	70069235	70069330
ENSE00003579743	70066934	70067134
ENSE00003620900	70070641	70070751
ENSE00003668426	70065965	70066084
ENSE00003698225	70067294	70067446
ENSE00003698693	70076521	70076574
ENSE00003898412	70077019	70077595

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 95.00.

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	95.00	gold quality
endometrium	UBERON:0001295	93.27	gold quality
smooth muscle tissue	UBERON:0001135	93.06	gold quality
right uterine tube	UBERON:0001302	92.88	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.49	gold quality
rectum	UBERON:0001052	91.78	gold quality
bone marrow	UBERON:0002371	91.77	gold quality
tonsil	UBERON:0002372	91.65	gold quality
descending thoracic aorta	UBERON:0002345	91.53	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.53	gold quality
skeletal muscle tissue	UBERON:0001134	91.48	gold quality
adenohypophysis	UBERON:0002196	91.15	gold quality
vermiform appendix	UBERON:0001154	91.12	gold quality
right coronary artery	UBERON:0001625	91.12	gold quality
left ovary	UBERON:0002119	91.04	gold quality
right ovary	UBERON:0002118	90.97	gold quality
body of uterus	UBERON:0009853	90.64	gold quality
primary visual cortex	UBERON:0002436	90.52	gold quality
ovary	UBERON:0000992	90.44	gold quality
lower esophagus mucosa	UBERON:0035834	90.33	gold quality
muscle tissue	UBERON:0002385	90.04	gold quality
prefrontal cortex	UBERON:0000451	90.03	gold quality
gall bladder	UBERON:0002110	89.91	gold quality
bone marrow cell	CL:0002092	89.75	gold quality
pituitary gland	UBERON:0000007	89.64	gold quality
monocyte	CL:0000576	89.53	gold quality
leukocyte	CL:0000738	89.39	gold quality
tibial nerve	UBERON:0001323	89.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.28	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.22	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, STAT5A

miRNA regulators (miRDB)

22 targeting SMN2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-487A-5P	98.85	69.37	993
HSA-MIR-487B-5P	98.85	69.48	987
HSA-MIR-382-3P	98.83	67.10	1074
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-4720-3P	98.50	68.88	988
HSA-MIR-4662A-3P	97.02	67.77	941
HSA-MIR-208A-3P	95.87	66.51	397
HSA-MIR-208B-3P	95.87	66.56	396

Literature-anchored findings (GeneRIF, showing 40)

• quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy (PMID:11791208)
• Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. (PMID:11839954)
• SMN2 is present in all SMA patients; it lacks SMN exon 7. A single non-polymorphic nucleotide difference is responsible for the alternative splicing patterns. (PMID:11875052)
• Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1 (PMID:11925564)
• SMN2 deletions could act as a susceptibility factor for sporadic lower motor neuron disease in adults (PMID:11993528)
• Absence of SMN2 may be a susceptibility factor for developing multifocal motor neuropathy. (PMID:12370479)
• Bifunctional antisense oligonucleotides provide a trans-acting splicing enhancer that stimulates gene expression in fibroblasts of spinal muscular atrophy patients. (PMID:12642665)
• A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy. (PMID:12833158)
• Valproic acid increases SMN2 protein level and has potential therapy for spinal muscular atrophy. (PMID:12915451)
• exon usage is regulated by the extended inhibitory context at the 5’ end of exon 7 in SMN2 protein in spinal muscular atrophy (PMID:14766219)
• The SMN2 gene copy number is more critical in determining the severity of the Spinal Muscular Atrophy Type III compared to the NAIP genotype. (PMID:15305106)
• Increasing SMN2 gene expression may be an effective strategy for the treatment of spinal muscular atrophy. (PMID:15772088)
• Aminoglycosides were found to restore detectable levels of SMN2 protein in fibroblasts of spinal muscular atrophy patients. (PMID:15790598)
• as SMN2 copy number increases, so does functional status in spinal muscular atrophy (PMID:15852397)
• identify synthetic compounds that increase the total amount of full-length SMN messenger RNA and protein arising from the SMN2 gene, thereby suppressing the deleterious effects of losing SMN1 (PMID:15944201)
• In spinal muscular atrophy (SMA), SMN2 is not able to compensate for the loss of SMN1 due to exclusion of exon 7. Here we describe a novel inhibitory element located immediately downstream of the 5’ splice site in intron 7. (PMID:16449646)
• mRNA and protein levels can be measured in the blood and used during clinical trials in spinal muscular atrophy. (PMID:16481599)
• Abnormal SMN1 gene copy numbers are a genetic risk factor in sporadic amyotrophic lateral sclerosis; There was no modulator effect of the SMN2 gene. (PMID:16931506)
• A single base change in intron 7 creates a high-affinity hnRNP A1 binding site, forming an exonic splicing silencer, leading to the exclusion of exon 7 and spinal muscular atrophy. (PMID:17307868)
• Findings suggest that the severity of SMA patients depend on the change of the SMN2 copy numbers. (PMID:17407069)
• results illustrate that an increased SMN2 gene copy number is associated with a milder SMA phenotype (PMID:17475491)
• optimized this strategy to the point that virtually all SMN2 pre-mRNA becomes correctly spliced (PMID:17505471)
• adenosine located 22 nucleotides upstream of exon 7is the major base pair used in splicing of intron 6 (PMID:17585203)
• SMN2 holds the promise for cure of SMA if skipping of exon 7 during pre-mRNA splicing of SMN2 could be prevented (PMID:17592254)
• SMN transcript instability does not play a role in the disease mechanism, suggesting that therapeutic modulation of messenger RNA degradation would not target a molecular defect in patients with spinal muscular atrophy. (PMID:17761657)
• No differences were found when comparing the SMN1 and SMN2 copy number distributions of the healthy population and HirD patients, and they do not therefore appear to be a susceptibility factor. (PMID:17850955)
• SMN2 exon 7 splicing is repressed by an hnRNPA1-dependent exonic splicing silencer. (PMID:17884807)
• Our finding that EIPA, an inhibitor of the Na+/H+ exchanger, can increase SMN protein expression in SMA cells provides a new direction for the development of drugs for SMA treatment. (PMID:17924536)
• Insufficient SMN2 protein arrests the post-natal development of the neuromuscular junction in spinal muscular atrophy patients. (PMID:18492800)
• SMN2 deficiency is associated in abnormal cardiogenesis. (PMID:18662980)
• Findings indicate close structural and functional similarities between fsmn and human SMN2 protein. (PMID:18703124)
• TDP-43 overexpression enhances exon 7 inclusion during the survival of motor neuron pre-mRNA splicing (PMID:18703504)
• Data demonstrate that hnRNP Q is a splicing modulator of SMN2, further underscoring the potential of hnRNP Q as a therapeutic target for spinal muscular atrophy. (PMID:18794368)
• Data show that SMN2 copy number predicts disease severity in spinal muscular atrophy. (PMID:18842367)
• reducing the competition between endogenous splices sites enhanced the efficiency of trans-splicing (PMID:18941511)
• CpG methylation of smn2 correlates with the severity of spinal muscular atrophy disease. (PMID:18971205)
• Study reports that C to T transition located in exon 7 in SMN2 compared to SMN1 results in increased uv light-mediated crosslinking of the splicing factor U2AF65 with the 3’ splice site of SMN1 intron 6 in HeLa nuclear extract. (PMID:19244360)
• The most frequent mutation is the biallelic deletion of exon 7 of the SMN1 gene. In SMA, SMN2 cannot compensate for the loss of SMN1, due to the exclusion of exon 7. (PMID:19271042)
• higher number of SMN2 copies makes the clinical symptoms more benign, and the NAIP gene deletion is associated with a more severe phenotype (PMID:19287802)
• SMN(A111G) mutant is capable of restoring snRNP assembly and rescue mice with spinal muscular atrophy. (PMID:19329542)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	smn1	ENSDARG00000018494
mus_musculus	Smn1	ENSMUSG00000021645
rattus_norvegicus	Smn1	ENSRNOG00000018067
drosophila_melanogaster	Smn	FBGN0036641
caenorhabditis_elegans	smn-1	WBGENE00004887

Paralogs (2): SMNDC1 (ENSG00000119953), SMN1 (ENSG00000172062)

Protein

Protein identifiers

Survival motor neuron protein — Q16637 (reviewed: Q16637)

Alternative names: Component of gems 1, Gemin-1

All UniProt accessions (5): Q16637, B4DP61, E7EQZ4, H0YBZ9, U3KPX7

UniProt curated annotations — full annotation on UniProt →

Function. The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Within the SMN complex, SMN1 acts as a structural backbone and together with GEMIN2 it gathers the Sm complex subunits. Binding of snRNA inside 5Sm ultimately triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. Ensures the correct splicing of U12 intron-containing genes that may be important for normal motor and proprioceptive neurons development. Also required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination. May also play a role in the metabolism of small nucleolar ribonucleoprotein (snoRNPs).

Subunit / interactions. Homooligomer; may form higher order homooligomers in the dimer to octamer range. Part of the core SMN complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP. Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG. Component of an import snRNP complex composed of KPNB1, RNUT1, SMN1 and ZNF259. Interacts with DDX20, FBL, NOLA1, RNUT1, SYNCRIP and with several spliceosomal snRNP core Sm proteins, including SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE and ILF3. Interacts with GEMIN2; the interaction is direct. Interacts with GEMIN3; the interaction is direct. Interacts with GEMIN8; the interaction is direct. Interacts with SNRPB; the interaction is direct. Interacts (via Tudor domain) with SNRPD1 (via C-terminus); the interaction is direct. Interacts with SNRPD2; the interaction is direct. Interacts (via Tudor domain) with SNRPD3 (via C-terminus); the interaction is direct. Interacts with SNRPE; the interaction is direct. Interacts with OSTF1, LSM10, LSM11 and RPP20/POP7. Interacts (via C-terminal region) with ZPR1 (via C-terminal region). Interacts (via Tudor domain) with COIL. Interacts with SETX; recruits SETX to POLR2A. Interacts with POLR2A (via the C-terminal domain (CTD)). Interacts with PRMT5. Interacts with XRN2. Interacts (via C-terminus) with FMR1 (via C-terminus); the interaction is direct and occurs in a RNA-independent manner. Interacts (via Tudor domain) with SF3B2 (‘Arg-508’-methylated form). Interacts with WRAP53/TCAB1. Interacts (via Tudor domain) with ELAVL4 in an RNA-independent manner; the interaction is required for localization of ELAVL4 to RNA granules. Interacts with FRG1. Does not homooligomerize. Does not interact with SNRPB.

Subcellular location. Nucleus. Gem. Cajal body. Cytoplasm. Cytoplasmic granule. Perikaryon. Cell projection. Neuron projection. Axon. Myofibril. Sarcomere. Z line.

Tissue specificity. Expressed in a wide variety of tissues. Expressed at high levels in brain, kidney and liver, moderate levels in skeletal and cardiac muscle, and low levels in fibroblasts and lymphocytes. Also seen at high levels in spinal cord. Present in osteoclasts and mononuclear cells (at protein level).

Disease relevance. Spinal muscular atrophy 1 (SMA1) [MIM:253300] A form of spinal muscular atrophy, a group of neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Autosomal recessive forms are classified according to the age of onset, the maximum muscular activity achieved, and survivorship. The severity of the disease is mainly determined by the copy number of SMN2, a copy gene which predominantly produces exon 7-skipped transcripts and only low amount of full-length transcripts that encode for a protein identical to SMN1. Only about 4% of SMA patients bear one SMN1 copy with an intragenic mutation. SMA1 is a severe form, with onset before 6 months of age. SMA1 patients never achieve the ability to sit. The disease is caused by variants affecting the gene represented in this entry. Spinal muscular atrophy 2 (SMA2) [MIM:253550] An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. It has intermediate severity, with onset between 6 and 18 months. Patients do not reach the motor milestone of standing, and survive into adulthood. The disease is caused by variants affecting the gene represented in this entry. Spinal muscular atrophy 3 (SMA3) [MIM:253400] An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Onset is after 18 months. Patients develop ability to stand and walk and survive into adulthood. The disease is caused by variants affecting the gene represented in this entry. Spinal muscular atrophy 4 (SMA4) [MIM:271150] An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Onset is in adulthood, disease progression is slow, and patients can stand and walk. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The Tudor domain mediates association with dimethylarginines, which are common in snRNP proteins.

Miscellaneous. The SMN gene is present in two highly homologous and functional copies (TelSMN/SMN1 and CenSMN/SMN2). The telomeric copy of SMN gene (TelSMN/SMN1) seems to be the SMA-determining gene while the centromeric copy seems unaffected. Primarily derived from SMN1 gene. Thought to be a non-functional protein that lacks the capacity to oligomerize and thus cannot interact with Sm proteins. Primarily derived from SMN2 gene.

Similarity. Belongs to the SMN family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q16637-1	SMN, Full-SMN	yes
Q16637-2	SMN-delta5, Iso5-SMN
Q16637-3	SMN-delta7, Iso7-SMN
Q16637-4	SMN-delta57, Iso57-SMN

RefSeq proteins (4): NP_059107, NP_075013, NP_075014, NP_075015 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002999	Tudor	Domain
IPR010304	SMN_Tudor	Domain
IPR040424	Smn1	Family
IPR047298	Tudor_SMN_eumet	Domain
IPR047313	SMN_C	Domain
IPR049481	SMN_G2-BD	Domain

Pfam: PF06003, PF20635, PF20636

UniProt features (82 total): mutagenesis site 25, sequence variant 15, modified residue 10, region of interest 8, compositionally biased region 5, helix 5, strand 4, splice variant 3, cross-link 2, turn 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
7W2P	X-RAY DIFFRACTION	1.15
4QQ6	X-RAY DIFFRACTION	1.75
1MHN	X-RAY DIFFRACTION	1.8
7W30	X-RAY DIFFRACTION	1.8
4GLI	X-RAY DIFFRACTION	1.9
5XJL	X-RAY DIFFRACTION	2.5
5XJU	X-RAY DIFFRACTION	2.58
5XJT	X-RAY DIFFRACTION	2.92
5XJR	X-RAY DIFFRACTION	3.12
5XJQ	X-RAY DIFFRACTION	3.28
5XJS	X-RAY DIFFRACTION	3.38
1G5V	SOLUTION NMR
2LEH	SOLUTION NMR
4A4E	SOLUTION NMR
4A4G	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16637-F1	67.45	0.25

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (12): 2, 4, 5, 8, 25, 28, 31, 69, 85, 187, 51, 209

Mutagenesis-validated functional residues (25):

Position	Phenotype
34	impairs gemin2 binding.
39	impairs gemin2 binding.
43	impairs gemin2 binding.
44	impairs gemin2 binding.
46	impairs gemin2 binding.
92	impairs binding to substrate containing dimethylated arginine.
102	impairs binding to substrate containing dimethylated arginine.
109	impairs binding to substrate containing dimethylated arginine.
127	impairs binding to substrate containing dimethylated arginine.
130	impairs binding to substrate containing dimethylated arginine.
132	impairs binding to substrate containing dimethylated arginine.
134–136	impairs binding to substrate containing dimethylated arginine.
134	impairs smn binding to rpp20/pop7. abolishes the interaction with elavl4. abolishes interaction with snrpd1 and snrpd3.
260	impairs homooligomerization.
263	impairs homooligomerization and gemin8 binding.
264	impairs homooligomerization.
266	impairs homooligomerization and gemin8 binding.
267	impairs homooligomerization.
268	impairs homooligomerization.
271	impairs homooligomerization.
272	impairs homooligomerization.
273	impairs gemin8 binding.
274	impairs homooligomerization.
275	impairs homooligomerization.
279	impairs homooligomerization.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-191859	snRNP Assembly
R-HSA-9754678	SARS-CoV-2 modulates host translation machinery
R-HSA-1643685	Disease
R-HSA-194441	Metabolism of non-coding RNA
R-HSA-5663205	Infectious disease
R-HSA-8953854	Metabolism of RNA
R-HSA-9679506	SARS-CoV Infections
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9705683	SARS-CoV-2-host interactions
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 116 (showing top): GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, GOBP_NEUROGENESIS, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, GOCC_NEURON_PROJECTION, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, GOBP_SPLICEOSOMAL_SNRNP_ASSEMBLY, REACTOME_METABOLISM_OF_RNA, GOCC_I_BAND, GOCC_SMN_COMPLEX, GOCC_GEMINI_OF_CAJAL_BODIES, GOCC_CAJAL_BODY, GOCC_NUCLEAR_BODY

GO Biological Process (7): spliceosomal complex assembly (GO:0000245), spliceosomal snRNP assembly (GO:0000387), DNA-templated transcription termination (GO:0006353), nervous system development (GO:0007399), RNA splicing, via transesterification reactions (GO:0000375), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (3): RNA binding (GO:0003723), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (15): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), Cajal body (GO:0015030), nuclear body (GO:0016604), Z disc (GO:0030018), axon (GO:0030424), SMN complex (GO:0032797), SMN-Sm protein complex (GO:0034719), cytoplasmic ribonucleoprotein granule (GO:0036464), neuron projection (GO:0043005), perikaryon (GO:0043204), Gemini of Cajal bodies (GO:0097504), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Metabolism of non-coding RNA	1
SARS-CoV-2-host interactions	1
Metabolism of RNA	1
Disease	1
Viral Infection Pathways	1
SARS-CoV Infections	1
SARS-CoV-2 Infection	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoplasm	3
mRNA splicing, via spliceosome	2
protein-RNA complex assembly	2
RNA processing	2
Sm-like protein family complex	2
DNA-templated transcription	1
RNA biosynthetic process	1
system development	1
RNA splicing	1
mRNA metabolic process	1
nucleic acid binding	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1
nucleoplasm	1
intracellular membraneless organelle	1
I band	1
neuron projection	1
SMN-Sm protein complex	1
SMN complex	1
ribonucleoprotein granule	1
plasma membrane bounded cell projection	1
neuronal cell body	1
nuclear body	1

Protein interactions and networks

STRING

2218 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMN2	GEMIN2	O14893	931
SMN2	HNRNPA1	P09651	889
SMN2	STRAP	Q9Y3F4	886
SMN2	NAIP	Q13075	875
SMN2	TRA2B	P62995	862
SMN2	TARDBP	Q13148	851
SMN2	FBL	P22087	850
SMN2	PLS3	P13797	846
SMN2	SERF1A	O75920	839
SMN2	COIL	P38432	836
SMN2	SYNCRIP	O60506	814
SMN2	FUS	P35637	811
SMN2	DDX20	Q9UHI6	782
SMN2	SRSF1	Q07955	767
SMN2	RBMX	P38159	763

IntAct

562 interactions, top by confidence:

A	B	Type	Score
SMN1	SMN1	psi-mi:“MI:0915”(physical association)	0.970
SMN1	SMN1	psi-mi:“MI:0407”(direct interaction)	0.970
SMN1	SMN1	psi-mi:“MI:2364”(proximity)	0.970
GEMIN2	SMN1	psi-mi:“MI:0915”(physical association)	0.960
SMN1	GEMIN2	psi-mi:“MI:0914”(association)	0.960
SNRNP70	SMN1	psi-mi:“MI:0407”(direct interaction)	0.860
SMN1	SNRPB	psi-mi:“MI:0914”(association)	0.850
SNRPD1	SMN1	psi-mi:“MI:0915”(physical association)	0.840
SMN1	SNRPD1	psi-mi:“MI:0915”(physical association)	0.840
SNRPD1	SMN1	psi-mi:“MI:0407”(direct interaction)	0.840
MED31	MED19	psi-mi:“MI:0914”(association)	0.840
FAM9B	SMN1	psi-mi:“MI:0915”(physical association)	0.780
SMN1	FAM9B	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (815): SMN2 (Two-hybrid), SMN2 (Two-hybrid), PPIG (Two-hybrid), POLR1C (Two-hybrid), HNRNPUL1 (Two-hybrid), CHTOP (Two-hybrid), BLOC1S6 (Two-hybrid), VPS28 (Two-hybrid), FAM9B (Two-hybrid), SMN1 (Affinity Capture-MS), SMN1 (Affinity Capture-MS), SMN2 (Affinity Capture-MS), GEMIN6 (Affinity Capture-MS), SMN2 (Affinity Capture-MS), LENG8 (Two-hybrid)

ESM2 similar proteins: A0M8S4, A0M8T5, B2RRE7, B9EJA2, O02771, O18870, O35876, P12757, P97801, Q00PJ1, Q01804, Q02225, Q07DV1, Q07DW4, Q07DX4, Q07DY4, Q07E15, Q07E28, Q07E41, Q09YG9, Q09YI1, Q09YJ3, Q09YK4, Q09YM8, Q108T9, Q16637, Q2IBA2, Q2IBB2, Q2IBD4, Q2IBE6, Q2IBF7, Q2IBF8, Q2QL82, Q2QLA2, Q2QLB3, Q2QLF8, Q2QLG9, Q3UWM4, Q4R4F8, Q5R431

Diamond homologs: O02771, O18870, O35876, O75940, P97801, Q16637, Q3T045, Q4QQU6, Q4R4F8, Q5R591, Q5RE18, Q66HC1, Q6DEY1, Q7ZV80, Q8BGT7, Q8HYB8, Q9W6S8, Q2HJG4, Q6NYG6, Q91W18, Q9VV74, Q5ZMS6, Q6NRP6, Q6P1U3, Q7SXW2, A4IF98, Q58EK5, Q5ZHV8, Q7ZVM9, Q9H7E2, Q9H9A7, P91399

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
MIB1	“down-regulates quantity by destabilization”	SMN1	ubiquitination
USP9X	“up-regulates quantity by stabilization”	SMN1	deubiquitination
PKA	“up-regulates quantity by stabilization”	SMN1	phosphorylation
FUS	“up-regulates activity”	SMN1	relocalization
MIB1	“down-regulates quantity by destabilization”	SMN1	polyubiquitination
SMN1	“form complex”	“SMN complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Metabolism of non-coding RNA	6	56.0×	2e-07
snRNP Assembly	8	24.9×	2e-07
mRNA Splicing - Minor Pathway	6	19.8×	3e-05
SARS-CoV-2 modulates host translation machinery	6	19.8×	3e-05
mRNA Polyadenylation	9	11.6×	8e-06
mRNA Splicing	7	11.3×	2e-04
Processing of Capped Intron-Containing Pre-mRNA	9	10.9×	1e-05
SARS-CoV-2-host interactions	6	10.5×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	9	74.7×	1e-12
U2-type prespliceosome assembly	5	44.6×	1e-05
mRNA splicing, via spliceosome	8	10.5×	1e-04
RNA splicing	8	10.1×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

10 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

968 predictions. Top by Δscore:

Variant	Effect	Δscore
5:70049764:CAG:C	donor_loss	1.0000
5:70049765:AGG:A	donor_loss	1.0000
5:70063404:A:AG	acceptor_gain	1.0000
5:70063405:C:G	acceptor_gain	1.0000
5:70063410:TCCAG:T	acceptor_gain	1.0000
5:70063411:CCAG:C	acceptor_gain	1.0000
5:70063413:A:AG	acceptor_gain	1.0000
5:70063413:AGAGC:A	acceptor_gain	1.0000
5:70063414:G:GC	acceptor_loss	1.0000
5:70063414:G:GG	acceptor_gain	1.0000
5:70063414:GA:G	acceptor_gain	1.0000
5:70063414:GAGC:G	acceptor_gain	1.0000
5:70063414:GAGCG:G	acceptor_gain	1.0000
5:70063483:TAAGG:T	donor_loss	1.0000
5:70063484:AAG:A	donor_loss	1.0000
5:70063485:AGG:A	donor_loss	1.0000
5:70063487:G:GA	donor_loss	1.0000
5:70063488:T:A	donor_loss	1.0000
5:70065955:A:AG	acceptor_gain	1.0000
5:70065956:T:G	acceptor_gain	1.0000
5:70065960:C:CA	acceptor_gain	1.0000
5:70065960:CGTAG:C	acceptor_loss	1.0000
5:70065961:GTAGC:G	acceptor_loss	1.0000
5:70065962:TAG:T	acceptor_loss	1.0000
5:70065963:A:AG	acceptor_gain	1.0000
5:70065963:AGCAT:A	acceptor_gain	1.0000
5:70065964:G:GA	acceptor_gain	1.0000
5:70065964:G:T	acceptor_loss	1.0000
5:70065964:GC:G	acceptor_gain	1.0000
5:70065964:GCA:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000307524 (5:70075579 C>G), RS1000357388 (5:70072771 T>G), RS1001817278 (5:70077276 C>T), RS1002122283 (5:70078107 T>C), RS1002874503 (5:70081993 G>C), RS1003397281 (5:70084408 T>C), RS1003900061 (5:70083278 A>G), RS1004234359 (5:70085451 T>C,G), RS1004732340 (5:70084569 T>C), RS1005396790 (5:70068212 C>T), RS1005907649 (5:70052207 A>G), RS1007650494 (5:70047695 T>C), RS1008008030 (5:70079103 A>C,G), RS1008329108 (5:70080662 G>A,C), RS1008919176 (5:70072561 A>G)

Disease associations

OMIM: gene MIM:601627 | disease phenotypes: MIM:253300, MIM:253400

GenCC curated gene-disease

Disease	Classification	Inheritance
spinal muscular atrophy, type III	Moderate	Autosomal recessive

Mondo (3): spinal muscular atrophy, type 1 (MONDO:0009669), spinal muscular atrophy, type III (MONDO:0009672), spinal muscular atrophy (MONDO:0001516)

Orphanet (3): Proximal spinal muscular atrophy type 1 (Orphanet:83330), Proximal spinal muscular atrophy (Orphanet:70), Proximal spinal muscular atrophy type 3 (Orphanet:83419)

HPO phenotypes

23 total (23 of 23 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001265	Hyporeflexia
HP:0001308	Tongue fasciculations
HP:0002378	Hand tremor
HP:0002398	Degeneration of anterior horn cells
HP:0002505	Loss of ambulation
HP:0003394	Muscle spasm
HP:0003438	Absent Achilles reflex
HP:0003444	EMG: chronic denervation signs
HP:0003547	Shoulder girdle muscle weakness
HP:0003621	Juvenile onset
HP:0003676	Progressive
HP:0003693	Distal amyotrophy
HP:0003701	Proximal muscle weakness
HP:0003724	Shoulder girdle muscle atrophy
HP:0003749	Pelvic girdle muscle weakness
HP:0006844	Absent patellar reflexes
HP:0007269	Spinal muscular atrophy
HP:0007289	Limb fasciculations
HP:0007340	Lower limb muscle weakness
HP:0008946	Pelvic girdle amyotrophy
HP:0008956	Proximal lower limb amyotrophy
HP:0025708	Early young adult onset

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009134	Muscular Atrophy, Spinal	C10.228.854.468; C10.574.562.500; C10.668.467.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293232 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

352 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 755,883 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL101	PHENYLBUTAZONE	4	59,455
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1042	CHOLECALCIFEROL	4	64,162
CHEMBL1070	NABUMETONE	4	55,063
CHEMBL1073	GLIPIZIDE	4	42,268
CHEMBL1082607	SALMETEROL XINAFOATE	4	15,201
CHEMBL1083993	AMIODARONE HYDROCHLORIDE	4	3,265
CHEMBL1086	DIBUCAINE	4	17,231
CHEMBL1089	PHENELZINE	4	18,793
CHEMBL1094	FELBAMATE	4	10,652
CHEMBL1103	FURAZOLIDONE	4	14,492
CHEMBL110691	CHLORMADINONE ACETATE	4	9,747
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1117	IDARUBICIN	4	136,065
CHEMBL1128	EDROPHONIUM CHLORIDE	4	20,117
CHEMBL1129	TRIFLURIDINE	4	24,647
CHEMBL1131	ACITRETIN	4	13,259
CHEMBL1134	DECAMETHONIUM BROMIDE	4	1,096
CHEMBL1159650	CLOBETASOL PROPIONATE	4
CHEMBL1200323	LABETALOL HYDROCHLORIDE	4
CHEMBL1200332	PROTRIPTYLINE HYDROCHLORIDE	4
CHEMBL1200334	MORICIZINE HYDROCHLORIDE	4
CHEMBL1200348	SULCONAZOLE NITRATE	4
CHEMBL1200425	PARGYLINE HYDROCHLORIDE	4
CHEMBL1200430	ESTRADIOL ACETATE	4
CHEMBL1200446	TRIPELENNAMINE HYDROCHLORIDE	4
CHEMBL1200469	PROMAZINE HYDROCHLORIDE	4
CHEMBL1200471	PYRITHIONE ZINC	4

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.85	Potency	1.4	nM	ESTRADIOL
8.80	Potency	1.6	nM	CHEMBL1483828
8.80	Potency	1.6	nM	CHEMBL1451171
8.74	Potency	1.8	nM	CHEMBL1452758
8.74	Potency	1.8	nM	CHEMBL1540153
8.70	Potency	2	nM	CHEMBL1456417
8.66	Potency	2.2	nM	CHEMBL1607331
8.66	Potency	2.2	nM	CHEMBL1514920
8.66	Potency	2.2	nM	CHEMBL1527163
8.66	Potency	2.2	nM	CHEMBL1466254
8.66	Potency	2.2	nM	CHEMBL1550144
8.66	Potency	2.2	nM	CHEMBL1407433
8.66	Potency	2.2	nM	CHEMBL1510564
8.60	Potency	2.5	nM	CHEMBL1372035
8.60	Potency	2.5	nM	CHEMBL1518885
8.60	Potency	2.5	nM	CHEMBL1444794
8.60	Potency	2.5	nM	CHEMBL1585974
8.60	Potency	2.5	nM	CHEMBL1481138
8.60	Potency	2.5	nM	CHEMBL1511055
8.55	Potency	2.8	nM	CHEMBL1528069
8.55	Potency	2.8	nM	CHEMBL3210258
8.55	Potency	2.8	nM	CHEMBL1301654
8.55	Potency	2.8	nM	CHEMBL1577858
8.55	Potency	2.8	nM	CHEMBL1539031
8.55	Potency	2.8	nM	CHEMBL80031
8.55	Potency	2.8	nM	CHEMBL1303998
8.55	Potency	2.8	nM	CHEMBL1319894
8.55	Potency	2.8	nM	CHEMBL1299989
8.55	Potency	2.8	nM	CHEMBL1437886
8.55	Potency	2.8	nM	CHEMBL1565769
8.55	Potency	2.8	nM	IMAZAQUIN
8.55	Potency	2.8	nM	CHEMBL1495008
8.55	Potency	2.8	nM	CHEMBL1338442
8.55	Potency	2.8	nM	CHEMBL1451563
8.55	Potency	2.8	nM	CHEMBL531401
8.55	Potency	2.8	nM	CHEMBL1311362
8.55	Potency	2.8	nM	CHEMBL1572506
8.55	Potency	2.8	nM	CHEMBL1482322
8.55	Potency	2.8	nM	CHEMBL475244
8.55	Potency	2.8	nM	CHEMBL1600218
8.55	Potency	2.8	nM	CHEMBL1375544
8.55	Potency	2.8	nM	CHEMBL110037
8.55	Potency	2.8	nM	CHEMBL1489768
8.55	Potency	2.8	nM	METHIOTHEPIN MESYLATE
8.55	Potency	2.8	nM	CHEMBL1531365
8.49	Potency	3.2	nM	CHEMBL1487880
8.49	Potency	3.2	nM	CHEMBL1607020
8.49	Potency	3.2	nM	CHEMBL1301914
8.49	Potency	3.2	nM	CHEMBL1568601
8.49	Potency	3.2	nM	CHEMBL1568896

PubChem BioAssay actives

74 with measured affinity, of 736 total; 36 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[6-[methyl-(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol	1934525: Modulation of human SMN2 level in NSC34 cells by ELISA	ec50	0.0040	uM
5-(1H-pyrazol-4-yl)-2-[6-(2,2,6,6-tetramethylpiperidin-4-yl)oxypyridazin-3-yl]phenol	1934525: Modulation of human SMN2 level in NSC34 cells by ELISA	ec50	0.0200	uM
2-[6-[methyl-(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl]-5-pyrazol-1-ylphenol	1934525: Modulation of human SMN2 level in NSC34 cells by ELISA	ec50	0.0200	uM
5-pyrazol-1-yl-2-[6-(2,2,6,6-tetramethylpiperidin-4-yl)oxypyridazin-3-yl]phenol	1934525: Modulation of human SMN2 level in NSC34 cells by ELISA	ec50	0.0300	uM
N-(1,3-benzothiazol-2-yl)-5-propan-2-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	0.1700	uM
N-(2-fluorophenyl)-5-propan-2-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	0.2600	uM
N-(1H-benzimidazol-2-yl)-5-propan-2-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	0.2600	uM
N-phenyl-5-propan-2-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	0.2800	uM
3-chloro-4-fluoro-N-[5-(1-hydroxycyclobutyl)-1,3-thiazol-2-yl]benzamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	0.2900	uM
N-(3-fluorophenyl)-5-propan-2-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	0.3400	uM
2-(6-piperidin-4-yloxypyridazin-3-yl)-5-pyrazol-1-ylphenol	1934525: Modulation of human SMN2 level in NSC34 cells by ELISA	ec50	0.3400	uM
5-propan-2-yl-N-pyridin-2-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	0.3600	uM
3-chloro-N-(5-cyclobutyl-1,3-thiazol-2-yl)-4-fluorobenzamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	0.5000	uM
N-(3-chloro-4-fluorophenyl)-4-methyl-5-propan-2-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	0.5000	uM
2,3-dihydroindol-1-yl-(5-propan-2-yl-1,2-oxazol-3-yl)methanone	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	0.7200	uM
5-propan-2-yl-N-(1,3-thiazol-2-yl)-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	0.7800	uM
N-(3-chlorophenyl)-5-propan-2-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	0.8600	uM
N-(4-methylphenyl)-5-propan-2-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	1.4000	uM
N-(3-chloro-4-fluorophenyl)-5-(2-methylpropyl)-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	1.5000	uM
3-chloro-4-fluoro-N-(2-propan-2-yl-1,3-thiazol-4-yl)benzamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	1.6000	uM
N-(3-methylphenyl)-5-propan-2-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	1.8000	uM
N-(4-fluorophenyl)-5-propan-2-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	1.8000	uM
N-(3-chloro-4-fluorophenyl)-5-propan-2-yl-1,2-oxazole-3-carboxamide	1372002: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	1.8000	uM
5-tert-butyl-N-(3-chloro-4-fluorophenyl)-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	1.9300	uM
N-(1-methylbenzimidazol-2-yl)-5-propan-2-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	2.6000	uM
N-(4-chlorophenyl)-5-propan-2-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	2.8000	uM
2-[6-(3,3-difluoropiperidin-4-yl)oxypyridazin-3-yl]-5-pyrazol-1-ylphenol	1934525: Modulation of human SMN2 level in NSC34 cells by ELISA	ec50	3.3000	uM
5-benzyl-N-(3-chloro-4-fluorophenyl)-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	3.5600	uM
N-(3-methoxyphenyl)-5-propan-2-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	3.6000	uM
N-(2-methylphenyl)-5-propan-2-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	5.4000	uM
3-chloro-4-fluoro-N-(3-propan-2-yl-1,2-oxazol-5-yl)benzamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	5.5000	uM
N-(2-chlorophenyl)-5-propan-2-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	6.2000	uM
N-(2-methoxyphenyl)-5-propan-2-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	7.3000	uM
N-(3-chloro-4-fluorophenyl)-5-ethyl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	8.8000	uM
3-chloro-4-fluoro-N-(5-propan-2-yl-1,2-oxazol-3-yl)benzamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	9.9000	uM
5-propan-2-yl-N-pyridin-3-yl-1,2-oxazole-3-carboxamide	1466983: Stabilization of human SMN protein expressed in HEK293 cells expressing SMN2 promoter after 24 hrs by luciferase reporter gene assay	ec50	9.9000	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
RG7800	increases splicing	1
antibiotic G 418	increases expression	1
beta-lapachone	decreases expression	1
ethylisopropylamiloride	affects expression, affects splicing	1
epigallocatechin gallate	increases expression, affects splicing	1
MDL 201053	decreases expression, decreases reaction, increases degradation, decreases degradation, increases expression	1
di-n-butylphosphoric acid	affects expression	1
aloxistatin	decreases expression, decreases reaction, increases degradation	1
Resveratrol	affects splicing, increases expression	1
Acetaminophen	increases expression	1
Amikacin	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	decreases expression	1
Curcumin	affects splicing, increases expression	1
Fluorouracil	decreases expression	1
Colforsin	increases expression	1
Paraquat	affects splicing, increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases methylation	1
Tobramycin	increases expression	1
Valproic Acid	increases expression	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

29 unique, capped per target: 23 binding, 6 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1613842	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Enhancers of SMN2 Splice Variant Expression. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL1826378	Binding	Activation of SMN in human fibroblast cells obtained from type 1 SMA patients assessed as protein punctuate bodies per 100 nuclei at 37 to 3000 nM	Discovery, synthesis, and biological evaluation of novel SMN protein modulators. — J Med Chem

Cellosaurus cell lines

69 cell lines: 39 finite cell line, 18 induced pluripotent stem cell, 12 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0X41	GM19123	Transformed cell line	Male
CVCL_5S83	GM23255	Transformed cell line	Male
CVCL_9X25	GM12552	Transformed cell line	Male
CVCL_B3NY	DMBi002-A	Induced pluripotent stem cell	Male
CVCL_BU77	GM22592	Transformed cell line	Male
CVCL_C1YG	AIDHC-13010	Finite cell line	Female
CVCL_C1YH	AIDHC-15224	Finite cell line	Female
CVCL_C1YU	AIDHC-00138	Finite cell line	Male
CVCL_C1YV	AIDHC-13148	Finite cell line	Male
CVCL_C1YW	AIDHC-13219	Finite cell line	Female

Clinical trials (associated diseases)

216 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01422200	PHASE4	COMPLETED	Flu Vaccine Study in Neuromuscular Patients 2011
NCT05232929	PHASE4	ACTIVE_NOT_RECRUITING	Long-term Follow-up Study of Risdiplam in Participants With Spinal Muscular Atrophy (SMA)
NCT05522361	PHASE4	ACTIVE_NOT_RECRUITING	Risdiplam in Patients With Spinal Muscular Atrophy Previously Treated With Nusinersen
NCT07448610	PHASE4	NOT_YET_RECRUITING	ASsessing The REAl-world Safety & Effectiveness of Spinal Muscular Atrophy Participants Treated With Intrathecal Onasemnogene Abeparvovec-brve (OAV101B) (ITVISMA®): A U.S. Pragmatic Multicenter Study (STREAM)
NCT05156320	PHASE3	COMPLETED	Efficacy and Safety of Apitegromab in Patients With Later-Onset Spinal Muscular Atrophy Treated With Nusinersen or Risdiplam
NCT05626855	PHASE3	ACTIVE_NOT_RECRUITING	Long-Term Safety & Efficacy of Apitegromab in Patients With SMA Who Completed Previous Trials of Apitegromab
NCT01671384	PHASE3	UNKNOWN	Valproate and Levocarnitine in Children With Spinal Muscular Atrophy
NCT02193074	PHASE3	TERMINATED	A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy
NCT02292537	PHASE3	COMPLETED	A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Participants With Later-onset Spinal Muscular Atrophy (SMA)
NCT02594124	PHASE3	COMPLETED	A Study for Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in Nusinersen (ISIS 396443) Investigational Studies
NCT03505099	PHASE3	COMPLETED	Pre-Symptomatic Study of Intravenous Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy (SMA) for Patients With Multiple Copies of SMN2
NCT03837184	PHASE3	COMPLETED	Single-Dose Gene Replacement Therapy Using for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies
NCT04042025	PHASE3	ACTIVE_NOT_RECRUITING	Long-term Follow-up Study of Patients Receiving Onasemnogene Abeparvovec-xioi
NCT04851873	PHASE3	COMPLETED	Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)
NCT05067790	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Learn About the Effect of Higher Doses of Nusinersen (BIIB058) Given as Injections to Participants With Spinal Muscular Atrophy (SMA) Who Were Previously Treated With Risdiplam (ASCEND)
NCT05335876	PHASE3	RECRUITING	Long-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 in Clinical Trials
NCT05337553	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy
NCT05386680	PHASE3	COMPLETED	Phase IIIb, Open-label, Multi-center Study to Evaluate Safety, Tolerability and Efficacy of OAV101 Administered Intrathecally to Participants With SMA Who Discontinued Treatment With Nusinersen or Risdiplam
NCT07265232	PHASE3	RECRUITING	Real World Clinical Effectiveness & Safety of Vesemnogene Lantuparvovec for Spinal Muscular Atrophy (SMA) in Low-middle Income Countries (LMIC).
NCT07444476	PHASE3	RECRUITING	A Study to Learn About Salanersen’s (BIIB115) Effects on Movement and Its Safety in Participants Aged 15 to 60 Years With Spinal Muscular Atrophy (SMA) Who Are Either New to SMA Treatment or Were Previously Treated With Risdiplam
NCT02227823	PHASE2	COMPLETED	Safety and Efficacy Study of Pyridostigmine on Patients With Spinal Muscular Atrophy Type 3
NCT02941328	PHASE2	COMPLETED	SPACE Trial: Pyridostigmine vs Placebo in SMA Types 2, 3 and 4
NCT03819660	PHASE2	TERMINATED	Long Term Safety of Amifampridine Phosphate in Spinal Muscular Atrophy 3
NCT03921528	PHASE2	COMPLETED	An Active Treatment Study of SRK-015 in Patients With Type 2 or Type 3 Spinal Muscular Atrophy
NCT07047144	PHASE2	RECRUITING	A Study to Evaluate How Apitegromab Works in Subjects Who Are Less Than 2 Years Old and Have Spinal Muscular Atrophy
NCT00004771	PHASE2	COMPLETED	Phase II Study of Leuprolide and Testosterone for Men With Kennedy’s Disease or Other Motor Neuron Disease
NCT00227266	PHASE2	COMPLETED	Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy
NCT00481013	PHASE2	COMPLETED	Valproic Acid in Ambulant Adults With Spinal Muscular Atrophy
NCT01028833	PHASE2	COMPLETED	Effects of Power Mobility on Young Children With Severe Motor Impairments
NCT01302600	PHASE2	COMPLETED	Safety and Efficacy of Olesoxime (TRO19622) in 3-25 Years SMA Patients.
NCT01839656	PHASE2	COMPLETED	A Study to Assess the Efficacy, Safety and Pharmacokinetics of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy (SMA)
NCT02386553	PHASE2	COMPLETED	A Study of Multiple Doses of Nusinersen (ISIS 396443) Delivered to Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy
NCT02462759	PHASE2	TERMINATED	A Study to Assess the Safety and Tolerability of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA).
NCT02644668	PHASE2	COMPLETED	A Study of CK-2127107 in Patients With Spinal Muscular Atrophy
NCT02876094	PHASE2	TERMINATED	Effect of Low-Dose Celecoxib on SMN2 in Patients With Spinal Muscular Atrophy
NCT03032172	PHASE2	COMPLETED	A Study of Risdiplam (RO7034067) in Adult and Pediatric Participants With Spinal Muscular Atrophy
NCT05794139	PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy of NMD670 in Ambulatory Adult Patients With Type 3 Spinal Muscular Atrophy
NCT07287982	PHASE2	RECRUITING	A Study to Assess the Safety, Tolerability, Efficacy, Pharmacokinetics, and Immunogenicity of Intravenous Administration of ARGX-119 in Pediatric Participants Aged 5 to Less Than 18 Years With Spinal Muscular Atrophy
NCT02122952	PHASE1	COMPLETED	Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1
NCT00374075	PHASE1	COMPLETED	Study of Safety and Dosing Effect on SMN Levels of Valproic Acid (VPA) in Patients With Spinal Muscular Atrophy