SOD1
superoxide dismutase 1, the group of Superoxide dismutases
Basic information
Region (hg38): 21:31659666-31668931
Previous symbols: [ "ALS", "ALS1" ]
Links
Phenotypes
GenCC
Source:
- amyotrophic lateral sclerosis type 1 (Strong), mode of inheritance: AD
- amyotrophic lateral sclerosis (Supportive), mode of inheritance: AD
- spastic tetraplegia and axial hypotonia, progressive (Limited), mode of inheritance: AR
- amyotrophic lateral sclerosis type 1 (Strong), mode of inheritance: AD
- amyotrophic lateral sclerosis type 1 (Strong), mode of inheritance: AR
- spastic tetraplegia and axial hypotonia, progressive (Strong), mode of inheritance: AR
- amyotrophic lateral sclerosis type 1 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Amyotrophic lateral sclerosis; Keratoconus; Spastic tetraplegia and axial hypotonia, progressive | AD/AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Evidence for pathogenicity is unclear in Keratoconus | Neurologic; Ophthalmologic | 8351519; 8105280; 8446170; 7647793; 8592323; 7887412; 15623718; 20577002; 22264771; 22292843; 22292847; 22722621; 31314961; 31332433 |
| Evidence for involvement with Keratoconus is unclear |
ClinVar
This is a list of variants' phenotypes submitted to
- Amyotrophic_lateral_sclerosis_type_1 (226 variants)
- not_provided (80 variants)
- SOD1-related_disorder (39 variants)
- Spastic_tetraplegia_and_axial_hypotonia,_progressive (10 variants)
- Inborn_genetic_diseases (10 variants)
- not_specified (7 variants)
- Motor_neuron_disease (5 variants)
- Amyotrophic_lateral_sclerosis (5 variants)
- Amyotrophic_lateral_sclerosis_1,_autosomal_recessive (3 variants)
- Abnormal_central_motor_function (1 variants)
- Amyotrophic_lateral_sclerosis_type_10 (1 variants)
- See_cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SOD1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000454.5. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 28 | 29 | ||||
| missense | 43 | 80 | 51 | 175 | ||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 6 | |||||
| splice donor/acceptor (+/-2bp) | 4 | |||||
| Total | 45 | 86 | 55 | 29 | 0 |
Highest pathogenic variant AF is 0.00002109613
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SOD1 | protein_coding | protein_coding | ENST00000270142 | 5 | 9310 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.177 | 0.773 | 125734 | 0 | 14 | 125748 | 0.0000557 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.838 | 65 | 87.0 | 0.747 | 0.00000444 | 1003 |
| Missense in Polyphen | 25 | 37.197 | 0.6721 | 458 | ||
| Synonymous | -1.27 | 43 | 33.6 | 1.28 | 0.00000185 | 303 |
| Loss of Function | 1.62 | 2 | 6.43 | 0.311 | 2.74e-7 | 83 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000231 | 0.000231 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000352 | 0.0000352 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000653 | 0.0000653 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems.;
- Disease
- DISEASE: Amyotrophic lateral sclerosis 1 (ALS1) [MIM:105400]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5- 10% of the cases. {ECO:0000269|PubMed:10400992, ECO:0000269|PubMed:10430435, ECO:0000269|PubMed:10732812, ECO:0000269|PubMed:11369193, ECO:0000269|PubMed:11535232, ECO:0000269|PubMed:12145308, ECO:0000269|PubMed:12402272, ECO:0000269|PubMed:12754496, ECO:0000269|PubMed:12963370, ECO:0000269|PubMed:14506936, ECO:0000269|PubMed:15056757, ECO:0000269|PubMed:18301754, ECO:0000269|PubMed:18378676, ECO:0000269|PubMed:18552350, ECO:0000269|PubMed:19741096, ECO:0000269|PubMed:21220647, ECO:0000269|PubMed:21247266, ECO:0000269|PubMed:27604643, ECO:0000269|PubMed:7496169, ECO:0000269|PubMed:7501156, ECO:0000269|PubMed:7647793, ECO:0000269|PubMed:7655468, ECO:0000269|PubMed:7655469, ECO:0000269|PubMed:7655471, ECO:0000269|PubMed:7700376, ECO:0000269|PubMed:7795609, ECO:0000269|PubMed:7836951, ECO:0000269|PubMed:7870076, ECO:0000269|PubMed:7881433, ECO:0000269|PubMed:7887412, ECO:0000269|PubMed:7951252, ECO:0000269|PubMed:7980516, ECO:0000269|PubMed:7997024, ECO:0000269|PubMed:8069312, ECO:0000269|PubMed:8179602, ECO:0000269|PubMed:8351519, ECO:0000269|PubMed:8446170, ECO:0000269|PubMed:8528216, ECO:0000269|PubMed:8682505, ECO:0000269|PubMed:8907321, ECO:0000269|PubMed:8938700, ECO:0000269|PubMed:8990014, ECO:0000269|PubMed:9101297, ECO:0000269|PubMed:9131652, ECO:0000269|PubMed:9455977, ECO:0000269|PubMed:9541385}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Prion diseases - Homo sapiens (human);Doxorubicin Pathway (Cancer Cell), Pharmacodynamics;Longevity regulating pathway - multiple species - Homo sapiens (human);Peroxisome - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Doxorubicin Pathway, Pharmacokinetics;Platinum Pathway, Pharmacokinetics/Pharmacodynamics;Oxidative Stress Pathway (Erythrocyte);Pathway_PA165980337;Oxidative Stress Pathway (Erythrocyte);Oxidative Stress Regulatory Pathway (Erythrocyte);Degradation of Superoxides;Selenium Micronutrient Network;Vitamin B12 Metabolism;Folate Metabolism;AGE-RAGE pathway;Dopamine metabolism;Amyotrophic lateral sclerosis (ALS);Nifedipine Activity;Copper homeostasis;Association Between Physico-Chemical Features and Toxicity Associated Pathways;One carbon metabolism and related pathways;Oxidative Stress;Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation;Detoxification of Reactive Oxygen Species;cardiac protection against ros;Cellular responses to stress;IL1;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Cellular responses to external stimuli;Hemostasis;the igf-1 receptor and longevity;FOXA1 transcription factor network;reactive oxygen species degradation;Validated nuclear estrogen receptor alpha network
(Consensus)
Recessive Scores
- pRec
- 0.954
Intolerance Scores
- loftool
- 0.126
- rvis_EVS
- -0.08
- rvis_percentile_EVS
- 47.79
Haploinsufficiency Scores
- pHI
- 0.434
- hipred
- Y
- hipred_score
- 0.647
- ghis
- 0.572
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.925
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Low | Low | Low |
Mouse Genome Informatics
- Gene name
- Sod1
- Phenotype
- hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype; skeleton phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; neoplasm; endocrine/exocrine gland phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- sod1
- Affected structure
- trunk
- Phenotype tag
- abnormal
- Phenotype quality
- morphology
Gene ontology
- Biological process
- activation of MAPK activity;response to superoxide;ovarian follicle development;positive regulation of cytokine production;placenta development;retina homeostasis;response to amphetamine;myeloid cell homeostasis;platelet degranulation;glutathione metabolic process;superoxide metabolic process;cellular iron ion homeostasis;spermatogenesis;embryo implantation;cell aging;sensory perception of sound;locomotory behavior;anterograde axonal transport;retrograde axonal transport;regulation of blood pressure;response to heat;response to organic substance;transmission of nerve impulse;removal of superoxide radicals;peripheral nervous system myelin maintenance;positive regulation of superoxide anion generation;regulation of T cell differentiation in thymus;response to carbon monoxide;cellular response to oxidative stress;interleukin-12-mediated signaling pathway;cellular response to potassium ion;regulation of multicellular organism growth;response to drug;response to hydrogen peroxide;superoxide anion generation;positive regulation of apoptotic process;positive regulation of catalytic activity;regulation of GTPase activity;negative regulation of neuron apoptotic process;response to ethanol;negative regulation of cholesterol biosynthetic process;regulation of protein kinase activity;regulation of organ growth;response to copper ion;muscle cell cellular homeostasis;thymus development;response to axon injury;hydrogen peroxide biosynthetic process;regulation of mitochondrial membrane potential;oxidation-reduction process;heart contraction;neurofilament cytoskeleton organization;relaxation of vascular smooth muscle;auditory receptor cell stereocilium organization;cellular response to cadmium ion;cellular response to ATP;reactive oxygen species metabolic process;response to antipsychotic drug;positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
- Cellular component
- extracellular region;extracellular space;nucleus;nucleoplasm;cytoplasm;mitochondrion;mitochondrial intermembrane space;mitochondrial matrix;lysosome;peroxisome;cytosol;plasma membrane;dense core granule;cytoplasmic vesicle;dendrite cytoplasm;protein-containing complex;neuronal cell body;myelin sheath;extracellular exosome;axon cytoplasm
- Molecular function
- superoxide dismutase activity;copper ion binding;protein binding;zinc ion binding;superoxide dismutase copper chaperone activity;protein phosphatase 2B binding;identical protein binding;protein homodimerization activity;Rac GTPase binding;chaperone binding