SMN1
Chr 5ARsurvival of motor neuron 1, telomeric
Also known as: BCD541, GEMIN1, SMA, SMA1, SMA2, SMA3, SMA4, SMA@
SMN1 makes the survival motor neuron protein; losing both copies causes spinal muscular atrophy (SMA), a recessive disease of about 1 in 10,000 births. It is a copy-number disease: about 95% of patients have no copy of SMN1 exon 7 at all, and almost all the rest have one deleted copy plus a small variant on the other. So the first test counts SMN1 copies, and sequencing comes second.
A near-identical neighbour, SMN2, differs by five bases; one of them makes most SMN2 transcripts skip exon 7, so each SMN2 copy adds a little working protein. The number of SMN2 copies is the main modifier: two copies most often means type 1 (never sits), three type 2, four type 3 — a strong prediction, not a certainty.
Newborn screening finds SMA before symptoms, and treatment is recommended at once for two, three or four SMN2 copies. Three treatments are approved: nusinersen (intrathecal), risdiplam (oral) and onasemnogene gene therapy. About 1 in 40–60 people is a carrier; a carrier with two SMN1 copies on the same chromosome ("2+0") tests normal on copy number, so a normal result lowers but does not remove the risk.
Primary Disease Associations & Inheritance
Clinical highlights
- Definitive · spinal muscular atrophy, type 1 · AR · Ambry Genetics
- Definitive · spinal muscular atrophy · AR · Myriad Women's Health
- Definitive · proximal spinal muscular atrophy · AR · Natera
- Strong · spinal muscular atrophy, type II · AR · Genomics England PanelApp
- onasemnogene abeparvovec (Zolgensma)AAV gene therapyApproved · FDA 2019
One-time AAV9-delivered functional SMN1 gene.
Delivery: One-time IV infusionEligibility: Under 2 years (IV label); greatest benefit pre-symptomatic; anti-AAV9 antibody negativeWeight-limited; transaminitis / thrombotic-microangiopathy monitoring
- onasemnogene abeparvovec-brve (Itvisma)AAV gene therapyApproved · FDA 2025
One-time AAV9 SMN1 gene replacement, intrathecal, fixed dose.
Delivery: One-time intrathecal injectionEligibility: Aged 2 or older with a confirmed SMN1 mutationFixed dose regardless of age or weight; warnings for liver and heart toxicity in adults with pre-existing conditions
- nusinersen (Spinraza)ASOApproved · FDA 2016
Splice-modulating ASO increasing SMN2 exon-7 inclusion.
Delivery: Intrathecal (loading, then every 4 months)Eligibility: All SMA types and agesHigh-dose regimen approved FDA 30 Mar 2026 (two 50 mg loading doses, then 28 mg every 4 months)
- risdiplam (Evrysdi)small moleculeApproved · FDA 2020
Oral SMN2 splicing modifier.
Delivery: Oral, once dailyEligibility: All ages, including newbornsHome administration; a 5 mg tablet (FDA Feb 2025) for ages 2 and older weighing over 20 kg
Therapeutic landscape as of 2026-07. Educational only. Investigational ≠ available; not medical advice or eligibility. Approved entries are precise; investigational program names/phases are conservative and move fast. Curated from FDA/EMA approvals and the clinical-trial literature; verify against current labeling + ClinicalTrials.gov.
ClinicalTrials.govSMA is a copy-number disease
What the SMN1 copy count means, and how SMN2 copies predict severity. Each bar is one chromosome 5.
SMN1 copies
0 copies
SMA — about 95% of patients have no copy of SMN1 exon 7.
1 copy
A carrier — or SMA, if the remaining copy carries a small variant (most of the other 5%). Sequence SMN1.
2 copies (1 + 1)
Usually not a carrier.
2 copies (2 + 0)
A carrier that a copy count cannot tell from 1 + 1 — why a normal result lowers, but does not remove, carrier risk.
SMN2 copies, in SMA
2 copies → most often type 1 (never sits)
79%3 copies → most often type 2 (sits, never walks)
54%4 copies → most often type 3 (walks)
88%
More SMN2 copies, milder disease — but the link is not absolute: some people with two copies are mildly affected. After newborn screening, treatment is recommended at once with two, three or four copies.
Sources: Prior et al., ACMG practice guideline, Genet Med 2008; Calucho et al., Neuromuscul Disord 2018 (3,459 patients); Cuscó et al., Neurol Genet 2020; Glascock et al., J Neuromuscul Dis 2020.
ClinVar Variant Classifications
0 submitted variants in ClinVar
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
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)
RECRUITINGStudy 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)
RECRUITINGA Study to Evaluate How Apitegromab Works in Subjects Who Are Less Than 2 Years Old and Have Spinal Muscular Atrophy
RECRUITINGA 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
RECRUITINGEvaluation of the Reproducibility of a Fatigability Test Fitted to Patients With Spinal Muscular Atrophy
RECRUITINGNeonatal Spinal Muscular Atrophy (SMA) Screening
RECRUITINGStudy of Safety, Tolerability and Efficacy of GB221 in Infants With Spinal Muscular Atrophy Type 1
RECRUITINGRegistry of Patients With a Diagnosis of Spinal Muscular Atrophy (SMA)
RECRUITINGUK SMA Patient Registry
RECRUITINGLong Read Analysis in Spinal Muscular Atrophy - LOREASI
RECRUITINGLong-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 in Clinical Trials
ACTIVE NOT RECRUITINGAdvanced Multi-omics and -System Approaches to Identify Novel Biomarkers for SMA
RECRUITINGExternal Resources
Links to major genomics databases and tools