SOD1
Chr 21ADARsuperoxide dismutase 1
Also known as: ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP, hSod1, homodimer
The protein functions as a cytoplasmic homodimer that converts superoxide radicals to molecular oxygen and hydrogen peroxide by binding copper and zinc ions. Mutations cause familial amyotrophic lateral sclerosis 1 and spastic tetraplegia with axial hypotonia through autosomal dominant and autosomal recessive inheritance patterns. The pathogenic mechanism involves dominant-negative effects where mutant protein disrupts normal cellular function.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
386 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 2 | 46 | 59 | 0 | 107 |
Likely Pathogenic | 7 | 73 | 2 | 0 | 82 |
VUS | 6 | 60 | 22 | 2 | 90 |
Likely Benign | 0 | 0 | 35 | 28 | 63 |
Benign | 0 | 0 | 19 | 0 | 19 |
Conflicting | — | 19 | |||
| Total | 15 | 179 | 137 | 30 | 380 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SOD1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Study to Investigate the Safety and Pharmacodynamics of a Single Intrathecal Injection (IT) of INS1202 in Participants With Amyotrophic Lateral Sclerosis (ALS)
RECRUITINGA Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
RECRUITINGEffects of Gender-Affirming Hormone Therapy on Cardiovascular, Metabolic, and Mental Health Outcomes in Transgender Adults.
NOT YET RECRUITINGA Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Participants With Superoxide Dismutase 1 (SOD-1) Amyotrophic Lateral Sclerosis (ALS)
RECRUITINGEffect of Exercise Type on Muscle Quality in Patients With OA, SARC and RA: an Explorative Study
NOT YET RECRUITINGA Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RAG-17 in Subjects With Amyotrophic Lateral Sclerosis (ALS) With Superoxide Dismutase Type 1 (SOD1) Gene Mutation
RECRUITINGExtended Study of RAG-17 in the Treatment of Amyotrophic Lateral Sclerosis Patients With SOD1 Gene Mutation
NOT YET RECRUITINGStudying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma
RECRUITINGSafety, Tolerability, and Exploratory Efficacy Study of Intrathecally Administered Gene Therapy AMT-162 in Adult Participants With SOD1 Amyotrophic Lateral Sclerosis (SOD1-ALS)
ACTIVE NOT RECRUITINGAmyotrophic Lateral Sclerosis (ALS) Families Project
RECRUITINGA Study of BIIB067 (Tofersen) Initiated in Clinically Presymptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation
ACTIVE NOT RECRUITINGAn Innovative Method in SAliva Samples for the Early Differential Diagnosis of High-impact NeuroDegenerative Diseases Through Raman Spectroscopy
ENROLLING BY INVITATIONExternal Resources
Links to major genomics databases and tools