SMN2

Chr 5AR

survival of motor neuron 2, centromeric

Also known as: BCD541, C-BCD541, GEMIN1, SMNC, TDRD16B

The SMN2 protein localizes to nuclear gems and forms complexes involved in small ribonucleoprotein biogenesis. Mutations in SMN2 serve as a modifier of spinal muscular atrophy type III, following an autosomal recessive inheritance pattern. Unlike its nearly identical telomeric copy SMN1, mutations in the centromeric SMN2 gene do not directly cause disease but can influence disease severity through gene conversion events and copy number variation.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 1.871 OMIM phenotype
Clinical SummarySMN2
Population Constraint (gnomAD)
Low constraint (pLI 0.10) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
11 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — SMN2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.87LOEUF
pLI 0.103
Z-score 0.20
OE 0.80 (0.231.87)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.44Z-score
OE missense 0.54 (0.271.24)
4 obs / 7.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.80 (0.231.87)
00.351.4
Missense OE0.54 (0.271.24)
00.61.4
Synonymous OE1.83
01.21.6
LoF obs/exp: 1 / 1.2Missense obs/exp: 4 / 7.4Syn Z: -0.96
DN
0.6649th %ile
GOF
0.3491th %ile
LOF
0.53top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SMN2 · 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

Muscular Atrophy, Spinal

A Study Evaluating the Effectiveness and Safety of Risdiplam Administered as an Early Intervention in Pediatric Participants With Spinal Muscular Atrophy After Gene Therapy

RECRUITING
NCT05861986Phase PHASE4Hoffmann-La RocheStarted 2024-05-30
Risdiplam
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 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)

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 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
Muscular Atrophy, Spinal

A Study of Risdiplam in Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy

ACTIVE NOT RECRUITING
NCT03779334Phase PHASE2Hoffmann-La RocheStarted 2019-08-07
Risdiplam
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
Muscular Atrophy, Spinal

A Study to Learn About the Safety and Effects of Salanersen (BIIB115) When Given to Babies With Spinal Muscular Atrophy (SMA) Who Were Previously Treated With Onasemnogene Abeparvovec

NOT YET RECRUITING
NCT07444450Phase PHASE3BiogenStarted 2026-09-04
SalanersenSham Procedure
Muscular Atrophy, Spinal

A Study Evaluating the Effectiveness and Safety of Risdiplam Administered in Pediatric Patients With Spinal Muscular Atrophy Who Experienced a Plateau or Decline in Function After Gene Therapy

RECRUITING
NCT05861999Phase PHASE4Hoffmann-La RocheStarted 2024-08-14
Risdiplam
Clinical Literature
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