SOD1
Superoxide Dismutase 1
Gene Summary
RefSeq / NCBIThe 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]
Clinical Phenotype
Familial ALS (fALS): upper and lower motor neuron degeneration causing progressive weakness, fasciculations, spasticity, and respiratory failure. SOD1-ALS accounts for ~20% of fALS and ~2% of all ALS.
Molecular Mechanism
Toxic gain-of-function from misfolded SOD1 protein aggregates, not loss of antioxidant activity. Misfolded SOD1 disrupts axonal transport, mitochondrial function, and triggers ER stress. The p.A4V variant is the most common and aggressive SOD1-ALS mutation in North America.
Clinical Hallmarks & Key Evidence
Tofersen (antisense oligonucleotide targeting SOD1 mRNA) was approved by FDA in 2023 for SOD1-ALS — the first gene-specific ALS therapy.
Miller TM et al. N Engl J Med. 2022;387(12):1099-1110.
SOD1-ALS typically spares frontotemporal cognition (unlike TDP-43/FUS-ALS), a distinguishing clinical feature used in prognosis and genetic counseling.
Phukan J et al. Lancet Neurol. 2012;11(3):232-40.
The p.A4V mutation causes a particularly aggressive course — median survival from symptom onset is only 12 months, far shorter than mean ALS survival of ~3 years.
Cudkowicz ME et al. Ann Neurol. 1997;41(2):210-21.
Associated Conditions
External Resources
Gene data compiled from the Washington University Neuromuscular Disease Center, NCBI Gene, and OMIM. For clinical use, always refer to primary sources.