SMN1

Chr 5AR

survival of motor neuron 1, telomeric

Also known as: BCD541, GEMIN1, SMA, SMA1, SMA2, SMA3, SMA4, SMA@

NCBI Gene: 6606ENSG00000172062UniProt: Q16637OMIM: 600354

The SMN1 protein localizes to nuclear gems and forms complexes involved in the biogenesis of small nuclear ribonucleoproteins (snRNPs). Mutations cause spinal muscular atrophy types 1-4, inherited in an autosomal recessive pattern. The pathogenic mechanism involves defective snRNP biogenesis leading to motor neuron degeneration.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 1.934 OMIM phenotypes
Clinical Summary— SMN1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
101 unique Pathogenic / Likely Pathogenic· 58 VUS of 246 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — SMN1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.93LOEUF
pLI 0.016
Z-score -0.63
OE 1.61 (0.48–1.93)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.06Z-score
OE missense 0.94 (0.53–1.68)
7 obs / 7.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.61 (0.48–1.93)
0≤0.351.4
Missense OE0.94 (0.53–1.68)
0≤0.61.4
Synonymous OE1.72
0≤1.21.6
LoF obs/exp: 2 / 1.2Missense obs/exp: 7 / 7.4Syn Z: -0.86

ClinVar Variant Classifications

246 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic66
Likely Pathogenic35
VUS58
Likely Benign18
Benign57
Conflicting10
66
Pathogenic
35
Likely Pathogenic
58
VUS
18
Likely Benign
57
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
28
12
26
0
66
Likely Pathogenic
16
14
5
0
35
VUS
3
26
25
4
58
Likely Benign
0
0
15
3
18
Benign
0
0
56
1
57
Conflicting
—10
Total47521278244

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SMN1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Spinal Muscular Atrophy (SMA)

Long-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 in Clinical Trials

RECRUITING
NCT05335876Phase PHASE3Novartis PharmaceuticalsStarted 2022-12-19
onasemnogene abeparvovec
Spinal Muscular Atrophy (SMA)

Study of the Safety and Efficacy of an Adeno-Associated Viral Vector Carrying the SMN Gene After a Single Intravenous Administration of Escalating Doses in Children With Spinal Muscular Atrophy (BLUEBELL)

RECRUITING
NCT05747261Phase PHASE1, PHASE2BiocadStarted 2023-02-02
ANB-004, dose 1ANB-004, dose 2ANB-004, dose 3
Spinal Muscular AtrophySMASpinal Muscular Atrophy Type 2

A Study to Evaluate How Apitegromab Works in Subjects Who Are Less Than 2 Years Old and Have Spinal Muscular Atrophy

RECRUITING
NCT07047144Phase PHASE2Scholar Rock, Inc.Started 2025-09-15
ApitegromabNusinersenRisdiplam
Spinal Muscular Atrophy (SMA)

Registry of Patients With a Diagnosis of Spinal Muscular Atrophy (SMA)

RECRUITING
NCT04174157Novartis PharmaceuticalsStarted 2018-09-25
Prospective observational registryZolgensma
Spinal Muscular Atrophy (SMA)

Long Read Analysis in Spinal Muscular Atrophy - LOREASI

RECRUITING
NCT07332702Phase NAUniversity Hospital, RouenStarted 2025-05-15
blood sample
Spinal Muscular Atrophy

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

RECRUITING
NCT07444476Phase PHASE3BiogenStarted 2026-04-03
Salanersen
Spinal AmyotrophyInfantile Spinal Muscular AtrophyJuvenile Spinal Muscular Atrophy

Evaluation of the Reproducibility of a Fatigability Test Fitted to Patients With Spinal Muscular Atrophy

RECRUITING
NCT06562283Phase NACentre Hospitalier Universitaire de Saint EtienneStarted 2024-12-06
Thumb testGrip testQuadriceps Intermittent Fatigue test (QIF test))
Invasive PreNatal Diagnosis in a Context of Family History of Single-gene Disorders, IncludingSickle Cell DiseaseCystic Fibrosis

Development of Non-Invasive Prenatal Diagnosis for Single Gene Disorders

RECRUITING
NCT06147414Assistance Publique - Hôpitaux de ParisStarted 2024-10-23
Blood sample
Spinal Muscular Atrophy

Spinal Muscular Atrophy Neonatal Screening Program

RECRUITING
NCT06310421IRCCS Burlo GarofoloStarted 2023-10-16
Screening SMA test
Muscular Atrophy, Spinal

A Study to Learn About Salanersen's (BIIB115) Effects on Movement and Its Safety When Given Before Symptoms Appear in Babies With Genetically Diagnosed Spinal Muscular Atrophy (SMA)

RECRUITING
NCT07221669Phase PHASE3BiogenStarted 2026-04-28
Salanersen
Spinal Muscular Atrophy Type I

Study of Safety, Tolerability and Efficacy of GB221 in Infants With Spinal Muscular Atrophy Type 1

RECRUITING
NCT07070999Phase PHASE1, PHASE2Gemma BiotherapeuticsStarted 2026-01-06
GB221
SMA - Spinal Muscular Atrophy

Safety and Efficacy Evaluation of GC101 Gene Therapy Via Intrathecal (IT) Injectionin the Treatment of Patients With Type 2 Spinal Muscular Atrophy (SMA) - Phase III

RECRUITING
NCT06971094Phase PHASE3GeneCradle IncStarted 2025-05-27
GC101 adeno-associated virus injection
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Stability and Oligomerization of Mutated SMN Protein Determine Clinical Severity of Spinal Muscular Atrophy
Niba ETE et al.·Genes (Basel)
2022
Genomic Variability in the Survival Motor Neuron Genes (SMN1 and SMN2): Implications for Spinal Muscular Atrophy Phenotype and Therapeutics Development
Butchbach MER·Int J Mol Sci
2021
A homozygous missense variant in the YG box domain in an individual with severe spinal muscular atrophy: a case report and variant characterization
Li L et al.·Front Cell Neurosci
2023Case report
Detection of SMN1 to SMN2 gene conversion events and partial SMN1 gene deletions using array digital PCR.
Stabley DL et al.·Neurogenetics
2021
The Carrier Frequency of Two SMN1 Genes in Parents of Symptomatic Children with SMA and the Significance of SMN1 Exon 8 in Carriers
Davidson JE et al.·Genes (Basel)
2023
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SMN1 mutation spectrum and functional analysis of novel SMN1 variants in a Chinese spinal muscular atrophy cohort.
Li GH et al.·J Hum Genet
2026Cohort
Low-dose AAV9-SMN1 with CNS-selective expression delivers efficacy and favorable safety in spinal muscular atrophy.
Yu Y et al.·Mol Ther
2026
First combined analysis of SMN1, SMN2, and NAIP copy numbers in Moroccan SMA patients and their correlation with disease severity.
Nmer S et al.·Mol Genet Metab Rep
2026Open AccessCohort
Digital droplet PCR for detection of SMN1 deletion in low-concentration fragmented cell-free DNA: a proof of concept study.
Parıltay E et al.·Scand J Clin Lab Invest
2026
SMN1 variants identified by false-positive SMA newborn screening tests: Therapeutic hurdles and functional and epidemiological solutions.
Wirth B et al.·Am J Hum Genet
2026Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients