SOD1 Gene (Superoxide Dismutase 1): Function, Mutations, and Associated Diseases
Comprehensive biomedical overview of SOD1, including genomic context, expression, disease associations, and mutation classifications.
Gene Information Card
| Symbol | SOD1 |
|---|---|
| Full Name | superoxide dismutase 1, soluble |
| Gene Type | protein-coding |
| Chromosomal Location | 21q22.11 |
| NCBI Gene ID | 6647 ncbi.nlm.nih.gov/gene/6647 |
| Ensembl ID | ENSG00000142168 |
| UniProt ID | P00441 |
| OMIM ID | 147450 |
| HGNC ID | 11186 |
| Aliases | ALS, ALS1, IPOA, SOD, homodimer |
Description
The SOD1 gene encodes the superoxide dismutase 1 enzyme, a cytosolic copper/zinc-binding protein that catalyzes the conversion of superoxide radicals to molecular oxygen and hydrogen peroxide, playing a critical role in cellular antioxidant defense. Mutations in SOD1 are a major cause of familial amyotrophic lateral sclerosis (ALS), leading to motor neuron degeneration through toxic gain-of-function mechanisms.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Amyotrophic Lateral Sclerosis (ALS) | Dominant toxic gain-of-function; mutant SOD1 misfolds and aggregates, causing oxidative stress, mitochondrial dysfunction, and neurotoxicity. | OMIM: 105400; ClinVar: pathogenic variants |
| SOD1-related familial ALS | Over 200 missense mutations disrupt protein stability and promote aggregation. | OMIM: 147450; COSMIC: somatic variants in some cancers |
| Spastic Paraplegia (rare) | Some SOD1 mutations cause lower motor neuron dysfunction with spasticity. | OMIM: 147450; case reports in ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 25.3 | High |
| Kidney | 20.1 | High |
| Brain | 15.7 | Medium |
| Heart | 12.4 | Medium |
| Skeletal Muscle | 8.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 30.5 | High expression |
| A549 | 18.2 | Moderate |
| SH-SY5Y | 22.0 | High (neuronal) |
| HeLa | 14.3 | Moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.A4V | Missense | ~50% of SOD1-ALS cases in North America | Aggregation-prone, rapid disease progression |
| p.H46R | Missense | Common in Japanese cohorts | Reduced enzymatic activity, slower progression |
| p.G93A | Missense | Most studied in transgenic models | Toxic gain-of-function, motor neuron death |
| p.D90A | Missense | Recessive in some populations, dominant in others | Variable penetrance, mild phenotype |
Mutation functional classification
Loss of Function (LOF)
Complete loss of SOD1 enzymatic activity is not sufficient to cause ALS; knockout mice do not develop motor neuron disease, indicating loss-of-function is not the primary mechanism.
Gain of Function (GOF)
Most ALS-linked mutations confer a toxic gain-of-function, leading to protein misfolding, aggregation, oxidative damage, and impairment of cellular processes.
Dominant Negative (DN)
Some mutations may exert a dominant-negative effect by forming heterodimers with wild-type SOD1, reducing overall enzymatic activity and promoting aggregation.
View complete mutation data：
Gene Ontology (GO)
| • superoxide dismutase activity | • copper ion binding |
| • zinc ion binding | • oxidation-reduction process |
| • response to oxidative stress | • removal of superoxide radicals |
Pathways
• Reactive oxygen species (ROS) metabolism
• Amyotrophic lateral sclerosis (ALS) pathway
• Oxidative stress response
• Copper/zinc homeostasis
Protein Summary
SOD1 is a 153-amino acid homodimeric enzyme that binds copper and zinc. It is primarily cytosolic but also localizes to mitochondria and nucleus. The protein converts superoxide radicals to hydrogen peroxide and oxygen, protecting cells from oxidative damage. Mutations cause protein misfolding and aggregation, leading to motor neuron degeneration in ALS.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SOD1 Knockout HEK293T Cell Line | EDJ-KQ78095 | Human | 6647 | Details Get a Quote |
| SOD1 Knockout HAP1 Cell Line | EDJ-KQ78116 | Human | 6647 | Details Get a Quote |
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