Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
Symbol SOD1 contributors: npt/pgu/shn - updated : 10-01-2023
HGNC name superoxide dismutase 1, soluble
HGNC id 11179
Type ubiquitous
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver   highly Homo sapiens
Endocrineadrenal gland   highly
 pancreas   highly
Skin/Tegumentskin   highly
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow   
cell lineage
cell lines
  • a masked DERL1 binding region
  • highly conserved intra-molecular disulfide bond , and enzymatically active form of SOD1 is equipped with copper and zinc ions and an intramolecular disulfide bond
  • conjugated MetalloP
    mono polymer homomer , dimer
    interspecies ortholog to Sod1, Mus musculus
    homolog to sod1, Danio rerio
    ortholog to SOD1, Pan troglodytes
    ortholog to Sod1, rattus norvegicus
  • Cu-Zn superoxide dismutase family
  • CATEGORY chaperone/stress , enzyme
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • present in the cytoplasm and nucleus and in the intermembrane space of mitochondria
  • mutant SOD1 accumulates inside the ER, where it forms insoluble high molecular weight species and interacts with the ER chaperone immunoglobulin-binding protein, and associated with mitochondria of motoneuronal cells to a much greater extent than wild-type SOD1, and this effect may depend on the oxidation of Cys residues
  • mitochondrial localization is dictated by its folding state, which is modulated by several interconnected factors
  • widely distributed in the cell cytosol and in the cell nucleus, consistent with it being a soluble cytosolic protein
  • basic FUNCTION
  • catabolic pathway of activated oxygen species,free radical detoxification
  • role in human placenta development (
  • may play a role in the regulation of cellular lifespan by p53 and may also regulate the death signals in cancer cells (
  • involved in the function of motor neuron
  • an important biological role for this enzyme in the preservation of mitochondrial homeostasis (
  • cuproenzyme that catalyzes the dismutation of the toxic superoxide anion, a byproduct of cellular respiration
  • functioning as a molecular switch that activates the ER stress response, which plays an important role in cellular homeostasis under zinc-deficient conditions
  • is a major copper-binding protein and regulates copper homeostasis in the cell
  • role for SOD1 in the regulation of RAC1-mediated lamellipodia pathway, a property fully retained by the two SOD1 mutants
  • modulates intestinal barrier integrity and intestinal homeostasis as an antioxidant enzyme
  • novel enzyme-independent function of SOD1 in intestinal stem cells (ISCs) growth under homeostasis
    PHYSIOLOGICAL PROCESS detoxification
    text a major defense against ROS by detoxifying the superoxide anion
    a component
    small molecule metal binding, cofactor,
  • copper Cu2+
  • zinc Zn2+
  • protein
  • copper chaperone for SOD1, CCS (
  • Dorfin physically bound and ubiquitylated various SOD1 mutants (
  • NEDL1 binds and ubiquitinates mutant SOD1 (
  • Hsp/Hsc70 interacts mutant SOD1 (
  • anti-apoptotic protein Bcl-2 (
  • HoxB2 binds mutant SOD1 (
  • chromogranin-A (CgA) and chromogranin-B (CgB) interact with mutant forms of SOD1 (
  • calcineurin, Cn (
  • Lysyl-tRNA synthetase, KARS (
  • gp78 (
  • glutathione peroxidase 2, GPX2 (
  • N-terminal portion of BCL2 between the BH4 and the loop domain
  • protects cortical neurons from hypoxia/reperfusion (I/R) injury by the increased SOD1 activity and the protective effect of MTRNR2L1 on neurons against I/R is concentration-dependent
  • CCS is the physiological partner for the complex mechanism of SOD1 maturation
  • mutant SOD1 interacting with HDAC6(likely mechanism of HDAC6 inhibition by mutant SOD1 is sequestration of HDAC6 into inclusions)
  • comprises a masked DERL1 binding region, that, under zinc-deficient conditions, adopts a mutant-like conformation exposing the DBR and inducing the homeostatic ER stress response
  • SOD1-DERL1 interaction contributes to the pathogenesis of ALS and is a promising drug target for ALS treatment
  • SOD1-interacting proteins were involved in multiple cellular functions such as protein quality control, cytoskeletal organization, and pathways involved in growth factor signaling and their downstream cascades
  • copper chaperone for SOD1 (CCS) is a dedicated and specific chaperone that assists SOD1 folding and maturation to produce the active enzyme
  • cell & other endoplasmic reticulum (
    inhibited by overexpression of X11alpha (
    Other regulated by SP1,EGR1 and WT1
    CCS-dependent and CCS-independent pathways control the activity, structure, and intracellular localization of SOD1
    ubiquitinated by mitochondrial ubiquitin ligase MITOL (
    SOD1 palmitoylation occurs prior to disulfide bonding during SOD1 maturation and palmitoylation is increased when disulfide bonding is delayed or decreased as observed for several sOD1 mutations
    corresponding disease(s) ALS1 , STHAP
    related resource An online database for ALS/SOD1 genetic mutations
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation   --over  
    an aberrant SOD1 mutant 32 kda is present (or associated with) sporadic or familial ALS pathology, suggesting a possible involvement in that pathology
    constitutional     --over  
    overexpressed in brain of down syndrome (temporal, occipital parietal cortex)
    Variant & Polymorphism
    Candidate gene
  • measurement of axonal transport may provide an early biomarker of disease progression and enable a timely diagnosis of motor neurons impairment, when the disease may be more responsive to therapeutic intervention
  • Therapy target
    neuromuscularlaterale amyotrophy sclerosis 
    gene silencing strategies targeting SOD1 may represent effective approaches for familial and sporadic ALS-related neurodegeneration
    neuromuscularlaterale amyotrophy sclerosis 
    by deleting NF-L, the major neurofilament subunit required for filament assembly, onset and progression of disease caused by familial ALS-linked SOD1 mutant G85R are significantly slowed, while selectivity of mutant-mediated toxicity for motor neurons is
    could be used as a potential agent in the treatment of hypercholesterolemia
    neuromuscularlaterale amyotrophy sclerosis 
    viral delivery of transcription-mediated siRNA is shown to suppress mutant SOD1 accumulation within muscle alone but to be insufficient to maintain grip strength, whereas delivery to both motor neurons and muscle is sufficient
    neuromuscularlaterale amyotrophy sclerosis 
    therapeutic interventions focusing on pharmacological as well as genetic regulations of copper homeostasis to modify the pathological process in SOD1-ALS
    neuromuscularlaterale amyotrophy sclerosis 
    anti-SOD1 antibodies, considered as ALS therapeutics, can act by blocking the uptake of SOD1, but also by blocking the toxic effects of intracellular SOD1
  • mutations in the Sod1 Drosophila gene resulte in striking neuropathology (
  • chronically inhibition of SOD1 by either antisense oligodeoxynucleotides or diethyldithiocarbamate in spinal cord organotypic cultures result in the apoptotic degeneration of spinal neurons, including motor neurons, over several weeks (
  • overexpression of Sod1 in transgenic mice affects motor neurons (
  • mice whith a incorporated transgene encoding for the human SOD1 mutation develop a form of motor neurone disease that closely resembles human forms of this disease (
  • In the FVB/N background, mice expressing mG86R SOD1 develop an ALS phenotype at approximately 100 days. However, when these mice were bred into a mixed background of C57Bl6/129Sv, the onset of the ALS phenotype was delayed 143 days to >2 years (
  • deregulation of Cdk5 activity associated with the hyperphosphorylation of tau and neurofilament proteins in mice expressing a mutant superoxide dismutase (G37R)) linked to amyotrophic lateral sclerosis (
  • transgenic C. elegans strains expressing mutant human SOD1 showed vulnerability to oxidative stress (
  • expression profiling of gene expression in SOD1-G93A transgenic mouse spinal cords indicates extensive glial activation coincident with the onset of paralysis at 3 months of age (
  • transgenic rat model harboring the G93A mutation overexpressing the SOD1 gene result in ALS-like motor neuron disease (
  • in G93A mice, mitochondrial respiration, electron transfer chain, and ATP synthesis were severely defective and evidence of oxidative damage to mitochondrial proteins and lipids at the time of onset of the disease (
  • SOD1 RNA interference (RNAi) induces senescence in normal human fibroblasts dependong on p53 induction (
  • motor neurons accumulate detergent-insoluble forms of SOD1 in transgenic mice expressing a SOD1 variant that mutates the four histidine residues that coordinately bind Cu (
  • adipose tissue accumulation, increased energy expenditure, and concomitant skeletal hypermetabolism ALS G93A mouse (
  • Overexpression of human SOD1 in mouse NIH3T3 fibroblasts increased SOD activity, enhanced intracellular generation of H2O2 and significantly stimulated angiogenesis by VEGF production (
  • transgenic mice expressing SOD1-L126Z display motor neuron disease characterized by accumulation of non-ubiquitinated detergent-insoluble SOD1-L126Z in spinal cords and aggregates of SOD1-L126Z in motor neuron somatodendritic compartments (
  • dysregulated redox stress in ALS mice caused by NADPH oxidases Nox1 and Nox2 significantly influenced the progression of motor neuron disease caused by mutant SOD1(G93A) expression (
  • in the spinal cord of transgenic mice expressing the familial ALS SOD1 gene mutation G93A, a decrease in constitutive proteasome subunits during disease progression and an increased immunoproteasome expression were found (
  • impairment of axonal transport of choline acetyltransferase and acetylcholine release in SOD1(G93A)-transgenic mouse (
  • E40K missense mutation in canin SOD1 gene lead to degenerative myelopathy (
  • G85R/WTSOD1 double transgenic mice had an acceleration of disease onset and shortened survival compared with G85R single transgenic mice, and there was an earlier appearance of pathological and immunohistochemical abnormalities (
  • Mitochondrial respiration, electron transfer chain, and ATP synthesis were severely defective in G93A mutated hSOD1 mice and oxidative damage to mitochondrial proteins and lipids were observed
  • Misfolded SOD1 protein was found primarily within degenerating motor neurons in ALS mouse models with the human G37R, G85R, and G93A SOD1 mutations
  • Mutant SOD1 preferentially associates with the cytoplasmic face of mitochondria from spinal cords of rats and mice expressing SOD1 mutations (
  • SOD1 total knockout (SOD1-deficient) mice display a high level of superoxide anion in the retinal ganglion cells leading to their degeneration (
  • Mutant SOD1 mice lacking motor neuron TrkB live a month longer than controls and retain motor function for a longer period, particularly in the early phase of the disease subserved by slowed motor neuron loss, persistence of neuromuscular junction integrity and reduced astrocytic and microglial reactivity within the spinal cord
  • inhibition of Shh signaling pathway exacerbated rat ischemic damage caused by permanent middle cerebral artery occlusion, which may be correlated with down-regulated expression of Gli1, Ptch1 and Sod1