SOD1
Chr 21ADARsuperoxide dismutase 1
Also known as: ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP, hSod1, homodimer
The protein encoded by this gene binds copper and zinc ions and is one of two isozymes responsible for destroying free superoxide radicals in the body. The encoded isozyme is a soluble cytoplasmic protein, acting as a homodimer to convert naturally-occuring but harmful superoxide radicals to molecular oxygen and hydrogen peroxide. The other isozyme is a mitochondrial protein. In addition, this protein contains an antimicrobial peptide that displays antibacterial, antifungal, and anti-MRSA activity against E. coli, E. faecalis, S. aureus, S. aureus MRSA LPV+, S. agalactiae, and yeast C. krusei. Mutations in this gene have been implicated as causes of familial amyotrophic lateral sclerosis. Rare transcript variants have been reported for this gene. [provided by RefSeq, Jul 2020]
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 — mechanism propensity
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.
References
ClinVar Variant Classifications
0 submitted variants 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.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Immuno-inflammatory Response of Erdosteine in COPD
NOT YET RECRUITINGMarkers of Oxidative Stress in Inflammatory Bowel Diseases: Risk Factors and Implications for a Dietetic Approach
ACTIVE NOT RECRUITINGFirst in Human (FIH) Study of ALN-SOD in Adult Participants With Amyotrophic Lateral Sclerosis Associated With Mutation in the SOD1 Gene (SOD1-ALS)
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 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 RECRUITINGExtended Study of RAG-17 in the Treatment of Amyotrophic Lateral Sclerosis Patients With SOD1 Gene Mutation
NOT YET RECRUITINGA Study to Investigate the Safety and Pharmacodynamics of a Single Intrathecal Injection (IT) of INS1202 in Participants With Amyotrophic Lateral Sclerosis (ALS)
RECRUITINGA Study of BIIB067 (Tofersen) Initiated in Clinically Presymptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation
ACTIVE NOT RECRUITINGAmyotrophic Lateral Sclerosis (ALS) Families Project
RECRUITINGA Randomized, Double-Blind, Placebo Controlled Study to Assess the Efficacy and Safety of SNP-610 for the Treatment of Patients With Non-alcoholic Steatohepatitis
NOT YET RECRUITINGMultilevel Exercise Response in Rowers
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools