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Atlas / Disease / spinal muscular atrophy, type IV

spinal muscular atrophy, type IV

disease
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Also known as adult-onset spinal muscular atrophySMA 4SMA type 4SMA type IVSMA-IVSMA4spinal muscular atrophy 4spinal muscular atrophy of adultsspinal muscular atrophy type 4spinal muscular atrophy, adult formspinal muscular atrophy, proximal, adult, autosomal recessivespinal muscular atrophy-4

Summary

spinal muscular atrophy, type IV (MONDO:0010056) is a disease caused by SMN1 (GenCC Strong), with 2 cohort genes and 2 clinical trials.

At a glance

  • Prevalence: Unknown (Europe) [Orphanet-validated]
  • Causal gene: SMN1 (GenCC Strong)
  • Cohort genes: 2
  • ClinVar variants: 8
  • Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namespinal muscular atrophy, type IV
Mondo IDMONDO:0010056
MeSHC563948
OMIM271150
Orphanet83420
DOIDDOID:0050529
ICD-11443229384
SNOMED CT85505000
UMLSC1838230
MedGen325364
GARD0000564
Is cancer (heuristic)no

Also known as: adult-onset spinal muscular atrophy · SMA 4 · SMA type 4 · SMA type IV · SMA-IV · SMA4 · spinal muscular atrophy 4 · spinal muscular atrophy of adults · spinal muscular atrophy type 4 · spinal muscular atrophy, adult form · spinal muscular atrophy, proximal, adult, autosomal recessive · spinal muscular atrophy, type IV · spinal muscular atrophy-4

Data availability: 8 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › spinal cord disorder › anterior horn disorder › spinal muscular atrophy › proximal spinal muscular atrophy › spinal muscular atrophy, type IV

Related subtypes (5): spinal muscular atrophy, type 1, spinal muscular atrophy, type III, spinal muscular atrophy, type II, lower motor neuron syndrome with late-adult onset, autosomal dominant childhood-onset proximal spinal muscular atrophy

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

8 retrieved; paginated sample, class counts are floors:

3 conflicting classifications of pathogenicity, 3 pathogenic, 1 uncertain significance, 1 pathogenic/likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
3906142NC_000005.10:g.71656113_71656167delMCCC2Pathogenicno assertion criteria provided
431179NC_000005.10:g.70946066_70946176delSMN1Pathogenicno assertion criteria provided
632989NM_000344.4(SMN1):c.835-1G>ASMN1Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
634947NM_000344.4(SMN1):c.399_402del (p.Glu134fs)SMN1Pathogeniccriteria provided, multiple submitters, no conflicts
1331398NM_000344.4(SMN1):c.*3+80T>GSMN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
2190592NM_000344.4(SMN1):c.861_864del (p.Arg288fs)SMN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
495829NM_000344.4(SMN1):c.835-3C>TSMN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
495833NM_000344.4(SMN1):c.865T>A (p.Cys289Ser)SMN1Uncertain significancecriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

GeneClassificationInheritanceDiseaseRecords
SMN1DefinitiveAutosomal recessivespinal muscular atrophy, type 112

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SMN1Orphanet:83330Proximal spinal muscular atrophy type 1
SMN1Orphanet:83418Proximal spinal muscular atrophy type 2
SMN1Orphanet:83419Proximal spinal muscular atrophy type 3
SMN1Orphanet:83420Proximal spinal muscular atrophy type 4
MCCC2Orphanet:63-methylcrotonyl-CoA carboxylase deficiency

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence2

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SMN1HGNC:11117ENSG00000172062Q16637Survival motor neuron proteingencc,clinvar
MCCC2HGNC:6937ENSG00000131844Q9HCC0Methylcrotonoyl-CoA carboxylase beta chain, mitochondrialclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SMN1Survival motor neuron proteinThe 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.
MCCC2Methylcrotonoyl-CoA carboxylase beta chain, mitochondrialCarboxyltransferase subunit of the 3-methylcrotonyl-CoA carboxylase, an enzyme that catalyzes the conversion of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA, a critical step for leucine and isovaleric acid catabolism.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

FamilyGenesFoldFDR
Other/Unknown21.8×0.312

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SMN1Other/UnknownnoTudor, SMN_Tudor, Smn1
MCCC2Other/UnknownnoCOA_CT_N, COA_CT_C, ClpP/crotonase-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)2
unknown0

Top tissues across cohort

TissueCohort genes
endocervix1
ganglionic eminence1
ventricular zone1
left ventricle myocardium1
right adrenal gland cortex1
secondary oocyte1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SMN1134markerventricular zone, ganglionic eminence, endocervix
MCCC2272ubiquitousmarkerleft ventricle myocardium, right adrenal gland cortex, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
SMN13,595
MCCC22,500

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
SMN1Q1663715
MCCC2Q9HCC014

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
3-Methylcrotonyl-CoA carboxylase deficiency12855.0×0.007MCCC2
Defects in biotin (Btn) metabolism11142.0×0.007MCCC2
Diseases of branched-chain amino acid catabolism1951.7×0.007MCCC2
Defective HLCS causes multiple carboxylase deficiency1815.7×0.007MCCC2
Biotin transport and metabolism1519.1×0.008MCCC2
Metabolism of non-coding RNA1317.2×0.010SMN1
Defects in vitamin and cofactor metabolism1300.5×0.010MCCC2
Branched-chain amino acid catabolism1237.9×0.012MCCC2
Disease213.1×0.014SMN1, MCCC2
SARS-CoV-2 modulates host translation machinery1112.0×0.019SMN1
snRNP Assembly1105.7×0.019SMN1
Metabolism of water-soluble vitamins and cofactors190.6×0.020MCCC2
SARS-CoV-2-host interactions159.5×0.027SMN1
Metabolism of vitamins and cofactors158.3×0.027MCCC2
Diseases of metabolism140.2×0.034MCCC2
SARS-CoV-2 Infection140.2×0.034SMN1
Metabolism of amino acids and derivatives133.8×0.038MCCC2
SARS-CoV Infections127.7×0.044SMN1
Metabolism of RNA120.8×0.055SMN1
Viral Infection Pathways115.4×0.070SMN1
Infectious disease112.4×0.083SMN1
Metabolism15.8×0.165MCCC2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
coenzyme A metabolic process11685.2×0.003MCCC2
L-leucine catabolic process11203.7×0.003MCCC2
DNA-templated transcription termination1766.0×0.003SMN1
branched-chain amino acid catabolic process1526.6×0.003MCCC2
spliceosomal complex assembly1300.9×0.004SMN1
spliceosomal snRNP assembly1290.6×0.004SMN1
nervous system development123.0×0.043SMN1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

SymbolExample approved molecule
SMN1BEPRIDIL

Top cohort targets by molecule count

SymbolMoleculesMax phase
SMN13524
MCCC200

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
BEPRIDIL4SMN1
PHENYLBUTAZONE4SMN1
PROGESTERONE4SMN1
CLOTRIMAZOLE4SMN1
CHOLECALCIFEROL4SMN1
NABUMETONE4SMN1
GLIPIZIDE4SMN1
SALMETEROL XINAFOATE4SMN1
AMIODARONE HYDROCHLORIDE4SMN1
DIBUCAINE4SMN1
PHENELZINE4SMN1
FELBAMATE4SMN1
FURAZOLIDONE4SMN1
CHLORMADINONE ACETATE4SMN1
AMOXAPINE4SMN1
IDARUBICIN4SMN1
EDROPHONIUM CHLORIDE4SMN1
TRIFLURIDINE4SMN1
ACITRETIN4SMN1
DECAMETHONIUM BROMIDE4SMN1
CLOBETASOL PROPIONATE4SMN1
LABETALOL HYDROCHLORIDE4SMN1
PROTRIPTYLINE HYDROCHLORIDE4SMN1
MORICIZINE HYDROCHLORIDE4SMN1
SULCONAZOLE NITRATE4SMN1
PARGYLINE HYDROCHLORIDE4SMN1
ESTRADIOL ACETATE4SMN1
TRIPELENNAMINE HYDROCHLORIDE4SMN1
PROMAZINE HYDROCHLORIDE4SMN1
PYRITHIONE ZINC4SMN1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

SymbolAssaysType breakdown
SMN129Binding:23, Functional:6
MCCC21Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

CompoundMax phaseCohort target (bioactivity)
BEPRIDIL4SMN1
PHENYLBUTAZONE4SMN1
PROGESTERONE4SMN1
CLOTRIMAZOLE4SMN1
CHOLECALCIFEROL4SMN1
NABUMETONE4SMN1
GLIPIZIDE4SMN1
SALMETEROL XINAFOATE4SMN1
AMIODARONE HYDROCHLORIDE4SMN1
DIBUCAINE4SMN1
PHENELZINE4SMN1
FELBAMATE4SMN1
FURAZOLIDONE4SMN1
CHLORMADINONE ACETATE4SMN1
AMOXAPINE4SMN1
IDARUBICIN4SMN1
EDROPHONIUM CHLORIDE4SMN1
TRIFLURIDINE4SMN1
ACITRETIN4SMN1
DECAMETHONIUM BROMIDE4SMN1
CLOBETASOL PROPIONATE4SMN1
LABETALOL HYDROCHLORIDE4SMN1
PROTRIPTYLINE HYDROCHLORIDE4SMN1
MORICIZINE HYDROCHLORIDE4SMN1
SULCONAZOLE NITRATE4SMN1
PARGYLINE HYDROCHLORIDE4SMN1
ESTRADIOL ACETATE4SMN1
TRIPELENNAMINE HYDROCHLORIDE4SMN1
PROMAZINE HYDROCHLORIDE4SMN1
PYRITHIONE ZINC4SMN1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1SMN1
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1MCCC2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

SymbolChEMBL assaysDrugged partners (top 3)
MCCC21—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified2

Top trials by phase / activity

NCTPhaseStatusTitle
NCT06300996Not specifiedACTIVE_NOT_RECRUITINGSpinal Cord Stimulation for the Treatment of Motor Deficits in People With Spinal Muscular Atrophy - Upper Limb
NCT05430113Not specifiedCOMPLETEDSpinal Cord Stimulation in Spinal Muscular Atrophy

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 69

This page pulls from 69 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgwasgwas_studyhgncicd11intactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot