SMN1

Summary

SMN1 (survival of motor neuron 1, telomeric, HGNC:11117) 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. However, mutations in this gene, the telomeric copy, are associated with spinal muscular atrophy; mutations in the centromeric copy do not lead to disease. The centromeric copy 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 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. Multiple transcript variants encoding distinct isoforms have been described.

Source: NCBI Gene 6606 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinal muscular atrophy, type 1 (Definitive, GenCC) — +4 more curated relationships
• Clinical variants (ClinVar): 183 total — 58 pathogenic, 24 likely-pathogenic
• Phenotypes (HPO): 53
• Druggable target: yes — 352 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000344

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11117
Approved symbol	SMN1
Name	survival of motor neuron 1, telomeric
Location	5q13.2
Locus type	gene with protein product
Status	Approved
Aliases	BCD541, SMNT, SMA1, SMA2, SMA3, GEMIN1, TDRD16A
Ensembl gene	ENSG00000172062
Ensembl biotype	protein_coding
OMIM	600354
Entrez	6606

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 15 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000351205, ENST00000380707, ENST00000503079, ENST00000506163, ENST00000506239, ENST00000507905, ENST00000510679, ENST00000513228, ENST00000514951, ENST00000518504, ENST00000625245, ENST00000870900, ENST00000932548, ENST00000932549, ENST00000932550, ENST00000932551, ENST00000932552, ENST00000932553, ENST00000932554, ENST00000932555

RefSeq mRNA: 3 — MANE Select: NM_000344 NM_000344, NM_001297715, NM_022874

CCDS: CCDS34181, CCDS34182, CCDS75256

Canonical transcript exons

ENST00000380707 — 9 exons

Exon	Start	End
ENSE00001593733	70946066	70946176
ENSE00001638255	70941389	70941508
ENSE00001688516	70938839	70938910
ENSE00001766361	70942358	70942558
ENSE00001885073	70952439	70953015
ENSE00003576392	70942718	70942870
ENSE00003611930	70944658	70944753
ENSE00003693452	70951941	70951994
ENSE00003899118	70925087	70925184

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 95.03.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	95.03	gold quality
ganglionic eminence	UBERON:0004023	94.56	gold quality
endocervix	UBERON:0000458	94.14	gold quality
cortical plate	UBERON:0005343	93.73	gold quality
left ovary	UBERON:0002119	93.60	gold quality
right ovary	UBERON:0002118	93.55	gold quality
calcaneal tendon	UBERON:0003701	93.26	gold quality
ovary	UBERON:0000992	93.25	gold quality
endometrium	UBERON:0001295	93.12	gold quality
uterine cervix	UBERON:0000002	92.69	gold quality
left uterine tube	UBERON:0001303	92.63	gold quality
ectocervix	UBERON:0012249	92.51	gold quality
tibial nerve	UBERON:0001323	92.03	gold quality
vagina	UBERON:0000996	91.95	gold quality
myometrium	UBERON:0001296	91.88	gold quality
adenohypophysis	UBERON:0002196	91.83	gold quality
body of uterus	UBERON:0009853	91.81	gold quality
placenta	UBERON:0001987	91.58	gold quality
right lobe of liver	UBERON:0001114	91.53	gold quality
thoracic mammary gland	UBERON:0005200	91.50	gold quality
body of pancreas	UBERON:0001150	91.45	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.41	gold quality
lymph node	UBERON:0000029	91.35	gold quality
right uterine tube	UBERON:0001302	91.31	gold quality
omental fat pad	UBERON:0010414	91.26	gold quality
mucosa of stomach	UBERON:0001199	91.25	gold quality
popliteal artery	UBERON:0002250	91.25	gold quality
tibial artery	UBERON:0007610	91.25	gold quality
islet of Langerhans	UBERON:0000006	91.21	gold quality
fallopian tube	UBERON:0003889	91.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.18

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BARX2, CEBPB, CREB1, ELK1, IRF6, JUN, MYC, RBPJ, SCX, SMAD3, SRF

miRNA regulators (miRDB)

22 targeting SMN1, 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)
• Analysis of stable HeLa cell lines has established that newly imported snRNPs selectively localize in a subset of Cajal bodies that contain the survival of motor neurons protein (SMN). (PMID:11792806)
• SMA is caused by the homozygous loss of SMN1. The aberrant splicing of exon 7 can’t provide protection from disease. A single non-polymorphic nucleotide difference is responsible for the alternative splicing pattern. (PMID:11875052)
• interacts with minute virus of mice NS1 and colocalizes in Cajal bodies induced by Parvovirus infection (PMID:11907229)
• Genetic study of SMA patients without homozygous SMN1 deletions: identification of compound heterozygotes and characterisation of novel intragenic SMN1 mutations. (PMID:11935338)
• SMN dosage analysis and risk assessment for spinal muscular atrophy (PMID:11992267)
• interacts with NS2 and colocalizes in infected nuclei at late times following MVM infection (PMID:12021369)
• Directly interacts with importin beta. The SMN complex persists until the final stages of cytoplasmic snRNP maturation. (PMID:12095920)
• SMN complex is associated with snRNPs throughout their cytoplasmic assembly pathway. (PMID:12192051)
• SMN is a novel telomerase-associated protein that is likely to function in human telomerase biogenesis (PMID:12221125)
• Infantile spinal muscular atrophy (SMA) is caused by mutations in the survival motor neuron (SMN)1 gene. We investigated the role of human (h) SMN protein on cell death in PC12 and Rat-1 cells. (PMID:12374765)
• SMN complex functions as a specificity factor essential for the efficient assembly of Sm proteins on U snRNAs and likely protects cells from illicit, and potentially deleterious, nonspecific binding of Sm proteins to RNAs (PMID:12459587)
• Homozygous deletion of the SMN1 gene in a Vietnamese spinal muscular dystrophy patient was found. (PMID:12657835)
• findings present SMN as a novel binding partner of Epstein-Barr virus nuclear antigen 2 (EBNA2) by showing that EBNA2 colocalizes with SMN in nuclear gems and that both proteins can be coimmunoprecipitated from cellular extract (PMID:12663808)
• Protein phosphatase 4 interacts with the Survival of Motor Neurons complex and enhances the temporal localisation of snRNP (PMID:12668731)
• SMN and coilin interact differentially with Cajal bodies and have roles in the pathway for reassembly of nucleoli and Cajal bodies following mitosis (PMID:12679382)
• Exon-7 was necessary for localization of SMN into the cytoplasm but was not sufficient for granule formation and transport. A cytoplasmic targeting signal within exon-7 was identified (PMID:12878704)
• Reduced SMN protein levels cause a reduction in the amount of its interacting proteins and of Htra2-beta1 in both discordant and non-discordant spinal muscular atrophy phenotypes. (PMID:14520560)
• Our data reveal a novel SMN/Gemin2 containing nuclear domain and support the idea that it represents the structural counterpart of gems seen in the light microscope. (PMID:14697339)
• Survival motor neuron (SMN) protein interacts with transcription corepressor mSin3A (PMID:14749338)
• expression of Epstein-Barr virus nuclear antigen-6 (EBNA-6) caused a redistribution of SMN protein to the EBNA-6 containing nuclear structures resulting in co-localization of SMN with EBNA-6 in B-lymphocytes (PMID:14972554)
• A homozygous deletion of exons 7 and 8 of the survival of motor neuron 1, telomeric (SMN1) gene was found, without neuronal apoptosis inhibitory protein (NAIP) gene deletion, leading to the diagnosis of spinal muscular atrophy (PMID:15119481)
• SMN binds to the arginine-rich N-terminus of FGF-2 (PMID:15222879)
• Two intragenic point mutations were identified in exon 3 (I116F, Q136E), affecting a very conserved region with the Tudor domain of SMN1. (PMID:15249625)
• identification of 10 mutations, including five mutations never reported previously and five recurrent mutations in spinal muscular atrophy patients; some of them are probably population-specific (PMID:15459957)
• SMN1 exon 6 and exon 7 synergistically regulate SMN distribution that may require specific exon 6 motifs but is independent of specific sequences in exon 7 (PMID:15526170)
• spinal muscular atrophy causing missense mutations identified in this study interfere with the reported interactions of SMN (PMID:15580564)
• A homozygous deletion of exons 7 and 8 of the survival of motor neuron 1, telomeric (SMN1) gene was found, without neuronal apoptosis inhibitory protein (NAIP) gene deletion, leading to the diagnosis of spinal muscular atrophy. (PMID:15726222)
• Gene activation was an early adaptive response to the lack of full-length SMN in mouse. In human Spinal Muscle Atrophy tissues, activation of this program was not observed, which could be ascribed to the reduction of full-length SMN. (PMID:16118268)
• Data show that SMN1 copy number could be detected precisely by real-time fluorescence quantitative PCR and the screening of gene carriers of spinal muscular atrophy could provide essential data for genetic counseling. (PMID:16331551)
• 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)
• We present the results of carrier studies in 33 relatives of the paternal branch of a spinal muscular atrophy patient with homozygous absence of the SMN1 gene. (PMID:16617248)
• Results show early survival motor neuron protein (SMN) expression in all neurons, and a progressive shift in SMN subcellular localization from mainly nuclear to cytoplasmic and then to axons during CNS maturation. (PMID:16651888)
• In SC anterior horn motoneurons at 13 weeks gestation, the soma, proximal neurites, and nucleus were immunostained. SMN was detected as early as 14 weeks of gestation in the forebrain. From 14-24 weeks, SMN was observed in the basal nucleus of Meynert. (PMID:16786553)
• Abnormal SMN1 gene copy numbers are a genetic risk factor in sporadic amyotrophic lateral sclerosis. (PMID:16931506)
• The findings of homozygous deletions of exons 7 and/or 8 of SMN1 gene confirms the diagnosis of SMA, even in patients with atypical clinical features. (PMID:16936383)
• Deletion of the SMN1 exon 7 is a major cause of spinal muscular atrophy in Malaysia (PMID:17250498)
• This study reported here that a novel mutation, W92S, in the Tudor domain affects the interaction of SMN with the target proteins. (PMID:17415510)
• screened patients with 1 SMN1 copy number for point mutations and identified 6 mutations (p.Y272C, pT274I, pI33IfsX6) (PMID:17475491)

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), SMN2 (ENSG00000205571)

Protein

Protein identifiers

Survival motor neuron protein — Q16637 (reviewed: Q16637)

Alternative names: Component of gems 1, Gemin-1

All UniProt accessions (4): Q16637, B4DP61, E7EQZ4, H0YBZ9

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 (3): NP_000335, NP_001284644, NP_075012 (=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: 211 (showing top): GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, GOBP_NEUROGENESIS, PUJANA_CHEK2_PCC_NETWORK, MUELLER_PLURINET, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, GOCC_NEURON_PROJECTION, GOBP_CELL_PROJECTION_ORGANIZATION, DANG_BOUND_BY_MYC, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOBP_SPLICEOSOMAL_SNRNP_ASSEMBLY, REACTOME_METABOLISM_OF_RNA, GOCC_I_BAND, GOCC_SMN_COMPLEX, GOCC_GEMINI_OF_CAJAL_BODIES

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
SMN1	GEMIN2	O14893	931
SMN1	HNRNPA1	P09651	889
SMN1	STRAP	Q9Y3F4	886
SMN1	NAIP	Q13075	875
SMN1	TRA2B	P62995	862
SMN1	TARDBP	Q13148	851
SMN1	FBL	P22087	850
SMN1	PLS3	P13797	846
SMN1	SERF1A	O75920	839
SMN1	COIL	P38432	836
SMN1	SYNCRIP	O60506	814
SMN1	FUS	P35637	811
SMN1	DDX20	Q9UHI6	782
SMN1	SRSF1	Q07955	767
SMN1	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 82 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	5	47.4×	7e-06
snRNP Assembly	7	22.1×	7e-06
mRNA Splicing - Minor Pathway	6	20.1×	4e-05
SARS-CoV-2 modulates host translation machinery	5	16.7×	7e-04
mRNA Polyadenylation	9	11.8×	7e-06
mRNA Splicing	7	11.5×	2e-04
Processing of Capped Intron-Containing Pre-mRNA	9	11.0×	1e-05
mRNA Splicing - Major Pathway	11	9.0×	7e-06

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	8	67.4×	1e-10
U2-type prespliceosome assembly	5	45.2×	1e-05
mRNA splicing, via spliceosome	8	10.6×	1e-04
RNA splicing	8	10.2×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	58
Likely pathogenic	24
Uncertain significance	54
Likely benign	13
Benign	12

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1335613	GRCh37/hg19 5q13.2(chr5:70247768-70247818)x0	Pathogenic
1679110	NM_000344.3:c.*3+32_*3+33insSVA	Pathogenic
1699219	NM_000344.4(SMN1):c.549del (p.Lys184fs)	Pathogenic
1699436	NM_000344.4(SMN1):c.291del (p.Lys97fs)	Pathogenic
2443947	NG_008691.1:g.32086_32087ins[N[1090];32074_32086]	Pathogenic
2506919	NM_000344.4(SMN1):c.801G>A (p.Trp267Ter)	Pathogenic
2571610	NM_000344.4(SMN1):c.835-8_835-5delinsG	Pathogenic
2684388	NM_000344.4(SMN1):c.43C>T (p.Gln15Ter)	Pathogenic
2690494	NM_000344.4(SMN1):c.22dup (p.Ser8fs)	Pathogenic
3239629	NM_000344.4(SMN1):c.245_267del (p.Lys82fs)	Pathogenic
3239630	NM_000344.4(SMN1):c.13del (p.Ser5fs)	Pathogenic
3239633	NM_000344.4(SMN1):c.603del (p.Pro203fs)	Pathogenic
3239634	NM_000344.4(SMN1):c.579del (p.Leu194fs)	Pathogenic
3239713	NM_000344.4(SMN1):c.490C>T (p.Gln164Ter)	Pathogenic
3239714	NM_000344.4(SMN1):c.850C>T (p.Gln284Ter)	Pathogenic
3239716	NM_000344.4(SMN1):c.827A>G (p.Tyr276Cys)	Pathogenic
3338105	NM_000344.4(SMN1):c.82-2596_723+467del	Pathogenic
3338271	NC_000005.10:g.(?70951941)(70951991_?)del	Pathogenic
3571473	NM_000344.4(SMN1):c.188C>A (p.Ser63Ter)	Pathogenic
3571588	NM_000344.4(SMN1):c.*3+6T>G	Pathogenic
3898747	GRCh37/hg19 5q13.2(chr5:70247768-70247818)x1	Pathogenic
39512	NM_000344.4(SMN1):c.389A>G (p.Tyr130Cys)	Pathogenic
39513	NM_000344.4(SMN1):c.388T>C (p.Tyr130His)	Pathogenic
4057250	NM_000344.4(SMN1):c.91dup (p.Ser31fs)	Pathogenic
431179	NC_000005.10:g.70946066_70946176del	Pathogenic
448429	NM_000344.4(SMN1):c.683T>A (p.Leu228Ter)	Pathogenic
457356	NC_000005.10:g.(?70951921)(70952011_?)del	Pathogenic
571461	NM_000344.4(SMN1):c.835-21_*3+17del	Pathogenic
583423	NC_000005.10:g.(?70951941)(70951991_?)del	Pathogenic
586627	NM_000344.4(SMN1):c.770_780dup (p.Gly261fs)	Pathogenic

SpliceAI

920 predictions. Top by Δscore:

Variant	Effect	Δscore
5:70938828:A:AG	acceptor_gain	1.0000
5:70938829:C:G	acceptor_gain	1.0000
5:70938834:TCCAG:T	acceptor_gain	1.0000
5:70938835:CCAG:C	acceptor_gain	1.0000
5:70938837:A:AC	acceptor_loss	1.0000
5:70938837:A:AG	acceptor_gain	1.0000
5:70938837:AGAGC:A	acceptor_gain	1.0000
5:70938838:G:GC	acceptor_loss	1.0000
5:70938838:G:GG	acceptor_gain	1.0000
5:70938838:GA:G	acceptor_gain	1.0000
5:70938838:GAGC:G	acceptor_gain	1.0000
5:70938838:GAGCG:G	acceptor_gain	1.0000
5:70938907:TAAGG:T	donor_loss	1.0000
5:70938908:AAG:A	donor_loss	1.0000
5:70938909:AGGT:A	donor_loss	1.0000
5:70938911:GTATG:G	donor_loss	1.0000
5:70938912:T:G	donor_loss	1.0000
5:70941379:A:AG	acceptor_gain	1.0000
5:70941380:T:G	acceptor_gain	1.0000
5:70941384:C:CA	acceptor_gain	1.0000
5:70941384:CGTAG:C	acceptor_loss	1.0000
5:70941385:GTA:G	acceptor_loss	1.0000
5:70941386:TA:T	acceptor_loss	1.0000
5:70941387:A:AG	acceptor_gain	1.0000
5:70941387:AGCAT:A	acceptor_gain	1.0000
5:70941388:G:GA	acceptor_gain	1.0000
5:70941388:GC:G	acceptor_gain	1.0000
5:70941388:GCA:G	acceptor_gain	1.0000
5:70941388:GCAT:G	acceptor_gain	1.0000
5:70941388:GCATG:G	acceptor_gain	1.0000

AlphaMissense

1922 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:70938873:T:A	L39Q	1.000
5:70938873:T:C	L39P	1.000
5:70938884:T:G	Y43D	1.000
5:70946141:T:A	W267R	1.000
5:70946141:T:C	W267R	1.000
5:70946154:G:A	G271D	1.000
5:70938857:T:A	W34R	0.999
5:70938857:T:C	W34R	0.999
5:70938859:G:C	W34C	0.999
5:70938859:G:T	W34C	0.999
5:70938860:G:C	D35H	0.999
5:70938861:A:C	D35A	0.999
5:70938863:G:C	D36H	0.999
5:70938864:A:C	D36A	0.999
5:70938864:A:G	D36G	0.999
5:70938864:A:T	D36V	0.999
5:70938881:G:C	A42P	0.999
5:70938884:T:A	Y43N	0.999
5:70938884:T:C	Y43H	0.999
5:70938893:G:C	A46P	0.999
5:70938894:C:A	A46D	0.999
5:70942416:C:A	A111D	0.999
5:70946133:T:C	L264S	0.999
5:70946143:G:C	W267C	0.999
5:70946143:G:T	W267C	0.999
5:70946144:T:G	Y268D	0.999
5:70946153:G:C	G271R	0.999
5:70946156:T:G	Y272D	0.999
5:70946166:G:A	G275D	0.999
5:70925164:T:C	F21L	0.998

dbSNP variants (sampled 300 via entrez): RS1000089734 (5:70959147 A>G), RS1000121261 (5:70948327 C>T), RS1000760080 (5:70950172 C>G,T), RS1001651962 (5:70950924 C>T), RS1001947457 (5:70951820 A>C,G), RS1003362988 (5:70955342 G>C), RS1003742893 (5:70956029 A>G,T), RS1004730092 (5:70958106 G>C), RS1005250083 (5:70957228 G>A), RS1005300354 (5:70944261 A>G), RS1006505778 (5:70960228 T>G), RS1006732564 (5:70948262 A>G), RS1006801887 (5:70960565 C>G), RS1007183918 (5:70961064 G>A,C), RS1007256698 (5:70944488 A>T)

Disease associations

OMIM: gene MIM:600354 | disease phenotypes: MIM:253300, MIM:253400, MIM:253550, MIM:271150

GenCC curated gene-disease

Disease	Classification	Inheritance
spinal muscular atrophy, type 1	Definitive	Autosomal recessive
spinal muscular atrophy	Definitive	Autosomal recessive
spinal muscular atrophy, type III	Strong	Autosomal recessive
spinal muscular atrophy, type II	Strong	Autosomal recessive
spinal muscular atrophy, type IV	Strong	Autosomal recessive

Mondo (5): spinal muscular atrophy (MONDO:0001516), spinal muscular atrophy, type 1 (MONDO:0009669), spinal muscular atrophy, type III (MONDO:0009672), spinal muscular atrophy, type II (MONDO:0009673), spinal muscular atrophy, type IV (MONDO:0010056)

Orphanet (5): Proximal spinal muscular atrophy (Orphanet:70), Proximal spinal muscular atrophy type 1 (Orphanet:83330), Proximal spinal muscular atrophy type 2 (Orphanet:83418), Proximal spinal muscular atrophy type 3 (Orphanet:83419), Proximal spinal muscular atrophy type 4 (Orphanet:83420)

HPO phenotypes

53 total (30 of 53 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001265	Hyporeflexia
HP:0001284	Areflexia
HP:0001290	Generalized hypotonia
HP:0001308	Tongue fasciculations
HP:0001324	Muscle weakness
HP:0001558	Decreased fetal movement
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0002093	Respiratory insufficiency
HP:0002205	Recurrent respiratory infections
HP:0002378	Hand tremor
HP:0002398	Degeneration of anterior horn cells
HP:0002421	Poor head control
HP:0002505	Loss of ambulation
HP:0002515	Waddling gait
HP:0002522	Areflexia of lower limbs
HP:0002878	Respiratory failure
HP:0003202	Skeletal muscle atrophy
HP:0003394	Muscle spasm
HP:0003438	Absent Achilles reflex
HP:0003444	EMG: chronic denervation signs
HP:0003445	EMG: neuropathic changes
HP:0003457	EMG abnormality
HP:0003547	Shoulder girdle muscle weakness
HP:0003557	Increased variability in muscle fiber diameter
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0003623	Neonatal onset
HP:0003676	Progressive

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D009134	Muscular Atrophy, Spinal	C10.228.854.468; C10.574.562.500; C10.668.467.500
C563948	Spinal Muscular Atrophy, Type IV (supp.)

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

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Smoke	decreases expression, increases abundance	2
Tobacco Smoke Pollution	increases expression, increases methylation	2
GSK-J4	increases expression	1
TL8-506	affects cotreatment, increases expression	1
beta-lapachone	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Caffeine	increases phosphorylation	1
Camptothecin	increases activity, increases response to substance, affects reaction	1
Cycloheximide	decreases reaction, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Niclosamide	decreases expression	1
Paraquat	decreases expression, decreases reaction, increases expression	1
Rotenone	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Cadmium Chloride	affects localization	1
2,4-Dinitrophenol	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

120 cell lines: 60 finite cell line, 33 induced pluripotent stem cell, 21 transformed cell line, 4 embryonic stem cell, 2 cancer 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_A259	KCL026	Embryonic stem cell	Male
CVCL_A9T6	CS84iSMA-n12B	Induced pluripotent stem cell	Female
CVCL_AD57	chHES-427	Embryonic stem cell	Female
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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03648658	PHASE4	UNKNOWN	Paracetamol Study in Patients With Low Muscle Mass
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
NCT04042025	PHASE3	ACTIVE_NOT_RECRUITING	Long-term Follow-up Study of Patients Receiving Onasemnogene Abeparvovec-xioi
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
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
NCT01302600	PHASE2	COMPLETED	Safety and Efficacy of Olesoxime (TRO19622) in 3-25 Years SMA Patients.
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
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