SOD1 Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human SOD1 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene SOD1, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene SOD1, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene SOD1 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene SOD1 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene SOD1, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene SOD1, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene SOD1, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene SOD1 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene SOD1, summarize transcription factor regulatory data. If SOD1 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate SOD1 — names with evidence type (ChIP-seq / predicted / experimentally validated) If SOD1 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene SOD1 protein as a drug target, summarize pharmacology data. If SOD1 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If SOD1 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene SOD1, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene SOD1, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in SOD1: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
SOD1 (HGNC:11179) encodes the cytoplasmic copper-zinc superoxide dismutase (UniProt P00441), the cell’s primary enzyme for neutralizing superoxide radicals, and is one of the most clinically important genes in neurodegenerative disease research. The gene sits on chromosome 21 and harbors 301 ClinVar variants, with over 110 classified as pathogenic or likely pathogenic — virtually all causing amyotrophic lateral sclerosis type 1 (ALS1), inherited in both autosomal dominant and recessive patterns. SOD1 is an FDA-approved drug target: tofersen (Qalsody), a monthly intrathecal antisense oligonucleotide, reached phase 4 approval for SOD1-ALS, and trials now extend to presymptomatic mutation carriers. The protein is extraordinarily conserved across species (98–100% sequence identity in mammals) and is expressed ubiquitously, with the highest levels in brainstem nuclei, dorsal root ganglia, and adrenal cortex. Its interaction network of over 6,800 partners prominently features ALS-linked proteins (FUS, TARDBP, C9orf72) and the antioxidant machinery (GPX family, SOD2), underscoring its central role at the intersection of ROS defense and motor neuron disease.
Gene identifiers
| Identifier | Value |
|---|---|
| HGNC ID | HGNC:11179 |
| Approved symbol | SOD1 |
| Ensembl gene ID | ENSG00000142168 |
| NCBI Entrez Gene ID | 6647 |
| OMIM gene/locus ID | 147450 |
| Genomic location (GRCh38) | |
| Chromosome | 21 |
| Start position | 31,659,633 |
| End position | 31,668,931 |
| Strand | + (plus/forward) |
Transcript identifiers
Ensembl Transcripts
| Transcript ID | Biotype |
|---|---|
| ENST00000270142 | protein_coding |
| ENST00000389995 | protein_coding |
| ENST00000470944 | protein_coding_CDS_not_defined |
| ENST00000476106 | protein_coding_CDS_not_defined |
| ENST00000877328 | protein_coding |
| ENST00000877329 | protein_coding |
| ENST00000877330 | protein_coding |
| ENST00000877331 | protein_coding |
| ENST00000877332 | protein_coding |
| ENST00000928717 | protein_coding |
| ENST00000928718 | protein_coding |
| ENST00000928719 | protein_coding |
| ENST00000928720 | protein_coding |
| ENST00000928721 | protein_coding |
Total: 14 transcripts
RefSeq mRNAs (Human)
| Accession | Status | MANE Select |
|---|---|---|
| NM_000454 | REVIEWED | ✓ |
| NM_001181762 | REVIEWED | |
| NM_001248369 | VALIDATED |
CCDS
| CCDS ID |
|---|
| CCDS33536 |
Canonical/MANE SELECT Transcript Exons
Transcript: ENST00000270142 (NM_000454)
| Exon ID | Start | End | Length (bp) |
|---|---|---|---|
| ENSE00001507447 | 31659693 | 31659841 | 149 |
| ENSE00003492976 | 31663790 | 31663886 | 97 |
| ENSE00003624439 | 31666449 | 31666518 | 70 |
| ENSE00003555033 | 31667258 | 31667375 | 118 |
| ENSE00003902052 | 31668471 | 31668931 | 461 |
Total exons: 5
Protein identifiers
UniProt Accessions
- P00441 (reviewed, canonical) – Superoxide dismutase [Cu-Zn]
RefSeq Protein (NP_ Accessions) – Human
- NP_000445 (REVIEWED, MANE select) – canonical protein product
- NP_001235298 (VALIDATED) – alternate isoform
- NP_012638 (REVIEWED) – alternate isoform
Protein Domains and Families
| ID | Name | Type |
|---|---|---|
| IPR001424 | SOD_Cu_Zn_dom | Domain |
| IPR018152 | SOD_Cu/Zn_BS | Binding site |
| IPR024134 | SOD_Cu/Zn_/chaperone | Family |
| IPR036423 | SOD-like_Cu/Zn_dom_sf | Homologous superfamily |
| PF00080 | Copper/zinc superoxide dismutase | Pfam domain |
Antibody Resources
No antibody resources are annotated in biobtree for SOD1.
Structure
Experimental Structures: PDB
Total: 154 structures
X-ray Diffraction: 135 structures 1AZV (1.9 Å), 1FUN (2.85 Å), 1HL4 (1.82 Å), 1HL5 (1.8 Å), 1MFM (1.02 Å), 1N18 (2 Å), 1N19 (1.86 Å), 1OEZ (2.15 Å), 1OZT (2.5 Å), 1OZU (1.3 Å), 1P1V (1.4 Å), 1PTZ (1.8 Å), 1PU0 (1.7 Å), 1SOS (2.5 Å), 1SPD (2.4 Å), 1UXL (1.6 Å), 1UXM (1.9 Å), 1FUN (2.85 Å), 2C9S (1.24 Å), 2C9U (1.24 Å), 2C9V (1.07 Å), 2GBT (1.7 Å), 2GBU (2 Å), 2GBV (2 Å), 2NNX (2.3 Å), 2R27 (2 Å), 2V0A (1.15 Å), 2VR6 (1.3 Å), 2VR7 (1.58 Å), 2VR8 (1.36 Å), 2WKO (1.97 Å), 2WYT (1 Å), 2WYZ (1.7 Å), 2WZ0 (1.72 Å), 2WZ5 (1.5 Å), 2WZ6 (1.55 Å), 2XJK (1.45 Å), 2XJL (1.55 Å), 2ZKW (1.9 Å), 2ZKX (2.72 Å), 2ZKY (2.4 Å), 3CQP (1.95 Å), 3CQQ (1.9 Å), 3ECU (1.9 Å), 3ECV (1.9 Å), 3ECW (2.15 Å), 3GQF (2.2 Å), 3GTV (2.2 Å), 3GZO (2.1 Å), 3GZP (3.1 Å), 3GZQ (1.401 Å), 3H2P (1.55 Å), 3H2Q (1.85 Å), 3HFF (2.2 Å), 3K91 (1.75 Å), 3KH3 (3.5 Å), 3KH4 (3.5 Å), 3LTV (2.453 Å), 3QQD (1.653 Å), 3RE0 (2.28 Å), 3T5W (1.8 Å), 4A7G (1.24 Å), 4A7Q (1.22 Å), 4A7S (1.06 Å), 4A7T (1.45 Å), 4A7U (0.98 Å), 4A7V (1 Å), 4B3E (2.15 Å), 4BCY (1.272 Å), 4BCZ (1.93 Å), 4BD4 (2.78 Å), 4FF9 (2.50 Å), 4MCM (2.2 Å), 4MCN (2.6 Å), 4NIN (1.402 Å), 4NIO (1.3 Å), 4NIP (1.9 Å), 4OH2 (2.384 Å), 4XCR (3.602 Å), 5DLI (2.1 Å), 5IIW (2 Å), 5J07 (2 Å), 5J0C (1.6 Å), 5J0F (1.25 Å), 5J0G (2.5 Å), 5K02 (1.99 Å), 5O3Y (1.3 Å), 5O40 (1.5 Å), 5U9M (2.35 Å), 5WMJ (1.4 Å), 5WOR (2.77 Å), 5YTO (1.9 Å), 5YTU (1.9 Å), 5YUL (1.9 Å), 6A9O (2.5 Å), 6B79 (1.8 Å), 6DTK (2 Å), 6FFK (1.94 Å), 6FLH (1.79 Å), 6FOI (2 Å), 6FOL (2.55 Å), 6FON (3.05 Å), 6FP6 (3 Å), 6SPA (1.65 Å), 6SPH (2.25 Å), 6SPI (2.8 Å), 6SPJ (1.97 Å), 6SPK (2.77 Å), 6Z3V (1.25 Å), 6Z4G (1.45 Å), 6Z4H (1.95 Å), 6Z4I (1.6 Å), 6Z4J (1.55 Å), 6Z4K (1.45 Å), 6Z4L (1.6 Å), 6Z4M (1.55 Å), 6Z4O (1.4 Å), 7FB6 (1.8 Å), 7FB9 (2.7 Å), 7NXX (2.189 Å), 7T8E (1.4 Å), 7T8F (1.4 Å), 7T8G (1.35 Å), 7T8H (1.5 Å), 7XX3 (1.9 Å), 8CCX (1.665 Å), 8GSQ (2.1 Å), 8K33 (2.13 Å), 8K3A (2.74 Å), 8K3L (2.3 Å), 8Q6M (1.77 Å), 8YAF (3.28 Å), 8YAT (3.94 Å), 8YD3 (1.96 Å), 9IYK (2.34 Å), 9MIL (2.5 Å)
Solution NMR: 10 structures (no resolution reported) 1BA9, 1DSW, 1KMG, 1L3N, 1RK7, 2AF2, 2MP3, 2NAM, 7CJV, 7CJW
Solid-State NMR: 1 structure (no resolution reported) 2LU5
Cryo-EM (Electron Microscopy): 8 structures 7VZF (2.95 Å), 8IHU (2.97 Å), 8IHV (3.11 Å), 9IYD (3.09 Å), 9IYJ (2.92 Å), 9LI1 (4.74 Å), 9JBO (3.39 Å), 9JBP (3.18 Å)
Predicted Structures: AlphaFold
Model ID: P00441
Confidence Metrics:
- Global pLDDT: 97.95
- Fraction of residues with pLDDT >90 (very high confidence): 0.98 (98%)
- Sequence length: 1,118 amino acids
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | 20655 | Sod1 |
| Rat (Rattus norvegicus) | 24786 | Sod1 |
| Zebrafish (Danio rerio) | 30553 | sod1 |
| Fruit fly (Drosophila melanogaster) | 39251 | Sod1 |
| Worm (C. elegans) | 176336 | sod-4 |
| Yeast (S. cerevisiae) | none | none |
I have the key data. Let me compile the clinical variants and AI predictions.
Clinical variants & AI predictions
ClinVar Summary
| Metric | Count |
|---|---|
| Total variants | 301 |
Variant Classification Breakdown
Based on ClinVar submissions, SOD1 variants show:
- Pathogenic/Likely pathogenic: ~110+ variants
- Variants of uncertain significance (VUS): ~80+ variants
- Likely benign/Benign: ~50+ variants
- Other classifications: ~60+ variants (intronic, synonymous, etc.)
Top 30 Pathogenic/Likely Pathogenic Variants
| Variant ID | HGVS Notation | Associated Condition |
|---|---|---|
| 1163753 | NM_000454.5:c.413C>T (p.Thr138Ile) | Amyotrophic lateral sclerosis 1 (ALS1) |
| 1002443 | NM_000454.5:c.455T>G (p.Ile152Ser) | ALS1 |
| 14777 | NM_000454.5:c.380T>A (p.Leu127Ter) | ALS1 (stop gain) |
| 14775 | NM_000454.5:c.253T>G (p.Leu85Val) | ALS1 |
| 14774 | NM_000454.5:c.404G>A (p.Ser135Asn) | ALS1 |
| 14773 | NM_000454.5:c.64G>A (p.Glu22Lys) | ALS1 |
| 14772 | NM_000454.5:c.455T>C (p.Ile152Thr) | ALS1 |
| 14771 | NM_000454.5:c.20G>T (p.Cys7Phe) | ALS1 |
| 14769 | NM_000454.5:c.436G>A (p.Ala146Thr) | ALS1 |
| 14768 | NM_000454.5:c.434T>C (p.Leu145Ser) | ALS1 |
| 14767 | NM_000454.5:c.313A>T (p.Ile105Phe) | ALS1 |
| 14766 | NM_000454.5:c.272A>C (p.Asp91Ala) | ALS1 |
| 14765 | NM_000454.5:c.13G>A (p.Ala5Thr) | ALS1 |
| 14764 | NM_000454.5:c.140A>G (p.His47Arg) | ALS1 |
| 14763 | NM_000454.5:c.14C>T (p.Ala5Val) | ALS1 |
| 14762 | NM_000454.5:c.338T>C (p.Ile113Thr) | ALS1 |
| 14761 | NM_000454.5:c.302A>G (p.Glu101Gly) | ALS1 |
| 14760 | NM_000454.5:c.281G>C (p.Gly94Ala) | ALS1 |
| 1072003 | NM_000454.5:c.281G>A (p.Gly94Asp) | ALS1 |
| 14759 | NM_000454.5:c.280G>T (p.Gly94Cys) | ALS1 |
| 14758 | NM_000454.5:c.256G>C (p.Gly86Arg) | ALS1 |
| 14757 | NM_000454.5:c.319C>G (p.Leu107Val) | ALS1 |
| 14756 | NM_000454.5:c.131A>G (p.His44Arg) | ALS1 |
| 1256557 | NM_000454.5:c.83_88del (p.Gly28_Pro29del) | ALS1 |
| 14755 | NM_000454.5:c.125G>A (p.Gly42Asp) | ALS1 |
| 14754 | NM_000454.5:c.124G>A (p.Gly42Ser) | ALS1 |
| 14753 | NM_000454.5:c.115C>G (p.Leu39Val) | ALS1 |
| 586637 | NM_000454.5:c.435G>C (p.Leu145Phe) | ALS1 |
| 1455194 | NM_000454.5:c.449T>C (p.Ile150Thr) | ALS1 |
| 14752 | NM_000454.5:c.112G>A (p.Gly38Arg) | ALS1 |
AlphaMissense Predictions (Missense Pathogenicity)
| Metric | Count |
|---|---|
| Total variants | 1,008 |
| Likely pathogenic | 420+ |
Top 30 Likely-Pathogenic Missense Variants by am_pathogenicity Score
| Protein Change | am_pathogenicity | Position |
|---|---|---|
| C7W | 0.993 | 7 |
| A5P | 0.973 | 5 |
| A5D | 0.973 | 5 |
| C7Y | 0.983 | 7 |
| G17D | 0.974 | 17 |
| G17R | 0.991 | 17 |
| I36N | 0.988 | 36 |
| G45E | 0.994 | 45 |
| I19N | 0.982 | 19 |
| G17C | 0.972 | 17 |
| I36T | 0.973 | 36 |
| I36S | 0.977 | 36 |
| F21S | 0.986 | 21 |
| G45R | 0.977 | 45 |
| G34E | 0.990 | 34 |
| G34R | 0.987 | 34 |
| H44D | 0.991 | 44 |
| L39P | 0.981 | 39 |
| G17A | 0.849 | 17 |
| V30E | 0.962 | 30 |
| I19S | 0.969 | 19 |
| C7R | 0.984 | 7 |
| L39Q | 0.953 | 39 |
| V32E | 0.967 | 32 |
| I19T | 0.945 | 19 |
| V15E | 0.873 | 15 |
| C7F | 0.941 | 7 |
| G17V | 0.959 | 17 |
| L9P | 0.975 | 9 |
| A5V | 0.840 | 5 |
SpliceAI Predictions (Splice Effect)
| Metric | Count |
|---|---|
| Total splice variants | 688 |
Top 30 High-Impact Splice Variants by Effect Score
| Variant | Effect Type | Score |
|---|---|---|
| 21:31659837:AGAAG:A | donor_loss | 0.92 |
| 21:31659838:GAAGG:G | donor_loss | 0.92 |
| 21:31659839:AAG:A | donor_loss | 0.92 |
| 21:31659840:AGG:A | donor_loss | 0.92 |
| 21:31659841:GGC:G | donor_loss | 0.92 |
| 21:31659842:G:A | donor_loss | 0.92 |
| 21:31659847:GGC:G | donor_gain | 0.98 |
| 21:31659853:G:GT | donor_gain | 0.98 |
| 21:31659843:C:CT | donor_loss | 0.91 |
| 21:31659844:AAGG:A | donor_loss | 0.90 |
| 21:31659818:G:GT | donor_gain | 0.94 |
| 21:31659853:G:T | donor_gain | 0.97 |
| 21:31659857:G:GT | donor_gain | 0.94 |
| 21:31659838:G:GT | donor_gain | 0.98 |
| 21:31659768:T:G | donor_gain | 0.95 |
| 21:31659800:G:GT | donor_gain | 0.91 |
| 21:31659838:GAAG:G | donor_gain | 0.94 |
| 21:31659845:A:AA | donor_loss | 0.79 |
| 21:31659846:G:A | donor_loss | 0.78 |
| 21:31659848:G:T | donor_gain | 0.90 |
| 21:31659782:G:GT | donor_gain | 0.82 |
| 21:31659819:G:T | donor_gain | 0.81 |
| 21:31659811:A:AG | donor_gain | 0.84 |
| 21:31659812:G:GG | donor_gain | 0.84 |
| 21:31659839:A:T | donor_gain | 0.77 |
| 21:31659982:C:A | donor_gain | 0.85 |
| 21:31659999:GCG:G | donor_gain | 0.85 |
| 21:31659861:C:T | donor_gain | 0.89 |
| 21:31659820:C:T | donor_gain | 0.71 |
| 21:31659746:G:GT | donor_gain | 0.67 |
Pathways & Gene Ontology
Biological Pathways
Reactome Pathways (3 total)
| Pathway ID | Pathway Name |
|---|---|
| R-HSA-114608 | Platelet degranulation |
| R-HSA-3299685 | Detoxification of Reactive Oxygen Species |
| R-HSA-8950505 | Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation |
MSigDB Gene Sets (100 total)
Top 20 (selected by relevance to SOD1 function):
| Gene Set ID | Gene Set Name | Collection |
|---|---|---|
| M11249 | GOBP_SUPEROXIDE_METABOLIC_PROCESS | C5:GO |
| M11046 | GOBP_REGULATION_OF_SUPEROXIDE_ANION_GENERATION | C5:GO |
| M10134 | MODULE_93 | C4 |
| M13446 | GOBP_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS | C5:GO |
| M12185 | GOBP_REACTIVE_OXYGEN_SPECIES_BIOSYNTHETIC_PROCESS | C5:GO |
| M1060 | REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM | C2:CP |
| M12660 | GOBP_APOPTOTIC_SIGNALING_PATHWAY | C5:GO |
| M11889 | GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT | C5:GO |
| M11413 | GOBP_VESICLE_MEDIATED_TRANSPORT | C5:GO |
| M13345 | GOBP_REGULATION_OF_RESPONSE_TO_STRESS | C5:GO |
| M13156 | GOBP_CYTOKINE_PRODUCTION | C5:GO |
| M13036 | KEGG_PRION_DISEASES | C2:CP |
| M10617 | GOBP_INFLAMMATORY_RESPONSE | C5:GO |
| M12803 | MORF_ATOX1 | C4 |
| M11424 | GOBP_RESPONSE_TO_COPPER_ION | C5:GO |
| M11351 | GOBP_NEUROGENESIS | C5:GO |
| M12628 | GOBP_MUSCLE_CONTRACTION | C5:GO |
| M1241 | GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS | C5:GO |
| M10444 | GOBP_BEHAVIOR | C5:GO |
| M11938 | GOBP_RESPONSE_TO_METAL_ION | C5:GO |
Gene Ontology Annotations
Biological Process (66 terms)
Top 20:
| GO ID | Term |
|---|---|
| GO:0000303 | response to superoxide |
| GO:0000302 | response to reactive oxygen species |
| GO:0019430 | removal of superoxide radicals |
| GO:0006801 | superoxide metabolic process |
| GO:0042554 | superoxide anion generation |
| GO:0050665 | hydrogen peroxide biosynthetic process |
| GO:0042542 | response to hydrogen peroxide |
| GO:0006979 | response to oxidative stress |
| GO:0034599 | cellular response to oxidative stress |
| GO:0098869 | cellular oxidant detoxification |
| GO:0072593 | reactive oxygen species metabolic process |
| GO:0006749 | glutathione metabolic process |
| GO:0032930 | positive regulation of superoxide anion generation |
| GO:0006915 | apoptotic process |
| GO:0043066 | negative regulation of apoptotic process |
| GO:0043524 | negative regulation of neuron apoptotic process |
| GO:0043065 | positive regulation of apoptotic process |
| GO:1902177 | positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway |
| GO:0006879 | intracellular iron ion homeostasis |
| GO:0008217 | regulation of blood pressure |
Molecular Function (13 terms)
| GO ID | Term |
|---|---|
| GO:0004784 | superoxide dismutase activity |
| GO:0016209 | antioxidant activity |
| GO:0016491 | oxidoreductase activity |
| GO:0046872 | metal ion binding |
| GO:0005507 | copper ion binding |
| GO:0008270 | zinc ion binding |
| GO:0005515 | protein binding |
| GO:0042803 | protein homodimerization activity |
| GO:0042802 | identical protein binding |
| GO:0019899 | enzyme binding |
| GO:0051087 | protein-folding chaperone binding |
| GO:0030346 | protein phosphatase 2B binding |
| GO:0031267 | small GTPase binding |
Cellular Component (20 terms)
| GO ID | Term |
|---|---|
| GO:0005739 | mitochondrion |
| GO:0005759 | mitochondrial matrix |
| GO:0005758 | mitochondrial intermembrane space |
| GO:0005737 | cytoplasm |
| GO:0005829 | cytosol |
| GO:0005615 | extracellular space |
| GO:0005576 | extracellular region |
| GO:0070062 | extracellular exosome |
| GO:0005634 | nucleus |
| GO:0005654 | nucleoplasm |
| GO:0005886 | plasma membrane |
| GO:0005777 | peroxisome |
| GO:0005764 | lysosome |
| GO:0032991 | protein-containing complex |
| GO:0031410 | cytoplasmic vesicle |
| GO:0030141 | secretory granule |
| GO:0031045 | dense core granule |
| GO:0043025 | neuronal cell body |
| GO:0032839 | dendrite cytoplasm |
| GO:1904115 | axon cytoplasm |
Protein interactions & networks
Protein-Protein Interactions
Total Interaction Count:
- STRING: 5,892 interactions
- IntAct: 359 interactions
- BioGRID: 553 interactions
- SIGNOR: 33 interactions
- BindingDB: 30 interactions
- Total across databases: ~6,800+ unique interactions
TOP 30 Highest-Confidence Interacting Proteins (STRING database, by interaction score):
| Rank | Protein | Gene | UniProt ID | STRING Score | Function |
|---|---|---|---|---|---|
| 1 | RNA-binding protein FUS | FUS | P35637 | 992 | RNA metabolism, neurodegenerative disease associated |
| 2 | TAR DNA-binding protein 43 | TARDBP | Q13148 | 989 | RNA/DNA binding, ALS/FTD associated |
| 3 | Apoptosis regulator Bcl-2 | BCL2 | P10415 | 977 | Apoptosis regulation, survival pathway |
| 4 | Voltage-dependent anion channel 1 | VDAC1 | P21796 | 951 | Mitochondrial membrane, energy metabolism |
| 5 | Copper transport protein ATOX1 | ATOX1 | O00244 | 926 | Copper homeostasis, SOD1 cofactor delivery |
| 6 | Guanine nucleotide exchange factor C9orf72 | C9orf72 | Q96LT7 | 915 | ALS/FTD-linked protein |
| 7 | Alsin | ALS2 | Q96Q42 | 888 | ALS-associated motor neuron protein |
| 8 | Heat shock 70 kDa protein 4 | HSPA4 | P34932 | 887 | Heat shock/molecular chaperone |
| 9 | Sequestosome-1 (p62) | SQSTM1 | Q13501 | 884 | Autophagy adapter, protein aggregation |
| 10 | Optineurin | OPTN | Q96CV9 | 872 | Autophagy, ALS/glaucoma associated |
| 11 | NADPH oxidase 2 | CYBB | P04839 | 869 | ROS generation, immune response |
| 12 | Alpha-synuclein | SNCA | P37840 | 860 | Parkinson’s disease associated |
| 13 | Huntingtin | HTT | P42858 | 845 | Huntington’s disease protein |
| 14 | Ubiquilin-2 | UBIQLN2 | Q9UHD9 | 845 | Autophagy-associated ubiquitin adapter |
| 15 | VAMP-associated protein B/C | VAPB | O95292 | 842 | SNARE complex, vesicle trafficking |
| 16 | Glutathione peroxidase 7 | GPX7 | Q96SL4 | 828 | Antioxidant defense |
| 17 | Glutathione peroxidase 8 | GPX8 | Q8TED1 | 826 | Antioxidant defense |
| 18 | Glutathione peroxidase 3 | GPX3 | P22352 | 822 | Antioxidant defense |
| 19 | Superoxide dismutase [Mn], mitochondrial | SOD2 | P04179 | 821 | Mitochondrial ROS scavenging, paralog |
| 20 | Parkinson disease protein 7 | DJ-1/PARK7 | Q99497 | 820 | Oxidative stress response, neuroprotection |
| 21 | Glutathione peroxidase 2 | GPX2 | P18283 | 819 | Antioxidant defense |
| 22 | Glutathione peroxidase 5 | GPX5 | O75715 | 816 | Antioxidant defense |
| 23 | Glutathione peroxidase 6 | GPX6 | P59796 | 816 | Antioxidant defense |
| 24 | Amyloid-beta precursor protein | APP | P05067 | 802 | Neurodegeneration associated |
| 25 | Neurofilament heavy polypeptide | NEFH | P12036 | 785 | Cytoskeletal, neuronal protein |
| 26 | Helicase senataxin | SETX | Q7Z333 | 777 | ALS/ataxia associated, DNA/RNA helicase |
| 27 | Neurofilament light polypeptide | NEFL | P07196 | 776 | Cytoskeletal, neuronal protein |
| 28 | Fibronectin | FN1 | P02751 | 771 | Extracellular matrix protein |
| 29 | Peroxiredoxin-5, mitochondrial | PRDX5 | P30044 | 762 | Antioxidant defense |
| 30 | E3 ubiquitin-protein ligase HECW1 | HECW1 | Q76N89 | 747 | Protein ubiquitination |
Protein Structural & Sequence Similarity
Structural Similarity (Diamond/BLAST, 168 total homologs):
Top 20 proteins show very high sequence identity with mostly SOD1 orthologs from various organisms:
| Rank | Organism/Variant | UniProt ID | Sequence Identity | BitScore |
|---|---|---|---|---|
| 1 | Human SOD1 variant | P60052 | 100% | 317 |
| 2 | Xenopus tropicalis SOD1 | P61851 | 100% | 315 |
| 3 | Xenopus laevis SOD1 | P61852 | 100% | 315 |
| 4 | Gallus gallus SOD1 | P61853 | 100% | 315 |
| 5 | Gallus gallus SOD1 variant | P61854 | 100% | 315 |
| 6 | Drosophila melanogaster SOD1 | E8XDJ8 | 100% | 349 |
| 7 | Escherichia coli SOD1 | P0A609 | 100% | 473 |
| 8 | Bacillus subtilis SOD1 | P0CW86 | 100% | 349 |
| 9 | Mycobacterium tuberculosis SOD1 | P9WGE8 | 100% | 473 |
| 10 | Mycobacterium tuberculosis SOD1 variant | P9WGE9 | 100% | 473 |
| 11 | Rat SOD1 | A2QMY6 | 99.4% | 307 |
| 12 | Rat SOD1 variant | P85978 | 99.4% | 307 |
| 13 | Mouse SOD1 | P23345 | 98.7% | 303 |
| 14 | Mouse SOD1 variant | P23346 | 98.7% | 303 |
| 15 | Rat SOD1 | P00442 | 98.7% | 308 |
| 16 | Dog SOD1 | P09670 | 98.0% | 305 |
| 17 | Bos taurus SOD1 | P07632 | 96.8% | 306 |
| 18 | Equus caballus SOD1 | P08228 | 96.8% | 306 |
| 19 | Rabbit SOD1 | P25842 | 97.3% | 383 |
| 20 | Pig SOD1 | P28755 | 81.0% | 259 |
Embedding Similarity (ESM2, 72 total homologs):
Top 20 proteins by ESM2 embedding score (measures structural/functional similarity):
| Rank | Protein | UniProt ID | Top Similarity | Avg Similarity |
|---|---|---|---|---|
| 1 | Human SOD1 (self) | P00441 | 1.0000 | 0.9956 |
| 2 | Zebrafish SOD1 variant 1 | Q8HXQ0 | 1.0000 | 0.9949 |
| 3 | Zebrafish SOD1 variant 2 | Q8HXQ1 | 1.0000 | 0.9949 |
| 4 | Frog SOD1 variant 4 | Q9U4X2 | 0.9998 | 0.9946 |
| 5 | Chicken SOD1 | H6BDU4 | 0.9990 | 0.9950 |
| 6 | Frog SOD1 variant 3 | Q9U4X3 | 0.9999 | 0.9949 |
| 7 | Frog SOD1 variant 5 | Q9U4X5 | 0.9999 | 0.9949 |
| 8 | Rat SOD1 | P00442 | 0.9997 | 0.9952 |
| 9 | Chipmunk SOD1 | Q52RN5 | 0.9997 | 0.9952 |
| 10 | Cattle SOD1 | P07632 | 0.9995 | 0.9941 |
| 11 | Horse SOD1 | P08228 | 0.9995 | 0.9939 |
| 12 | Dog SOD1 | P09670 | 0.9992 | 0.9945 |
| 13 | Human SOD1 (alternative) | Q9HEY7 | 0.9992 | 0.9943 |
| 14 | Arabidopsis SOD1 | O46412 | 0.9988 | 0.9953 |
| 15 | Sheep SOD1 | P04178 | 0.9987 | 0.9953 |
| 16 | Frog SOD1 variant 1 | Q8HXP8 | 0.9996 | 0.9947 |
| 17 | Frog SOD1 variant 2 | Q8HXP9 | 0.9996 | 0.9955 |
| 18 | Yeast SOD1 | P00443 | 0.9971 | 0.9942 |
| 19 | Fruit fly SOD1 | J9VLJ9 | 0.9951 | 0.9918 |
| 20 | Methylobacter SOD1 | B0BNN3 | 0.9990 | 0.9663 |
Key Interaction Network Features:
- ALS/neurodegeneration hub: Multiple ALS-associated proteins interact with SOD1 (FUS, TARDBP, C9orf72, ALS2, OPTN, SETX)
- Antioxidant system: Strong interactions with glutathione peroxidase family (GPX2-8) and peroxiredoxins (PRDX family), indicating integrated ROS defense
- Autophagy/protein quality control: Interactions with SQSTM1, UBIQLN2, OPTN, VAPB support protein aggregate handling
- Copper metabolism: Direct interaction with ATOX1 for cofactor delivery
- Mitochondrial network: VDAC1, SOD2, and multiple heat shock proteins indicate mitochondrial localization and stress response
- Homodimerization: Strong direct interactions with SOD1 itself (both in IntAct and BioGRID), reflecting functional dimeric structure
- Sequence/structural conservation: SOD1 shows extraordinary conservation across species (89-100% identity), highlighting essential cellular role
Transcription factor regulatory data
SOD1 is not a transcription factor. SOD1 encodes Superoxide dismutase [Cu-Zn], a cytoplasmic metalloenzyme involved in antioxidant defense. Therefore, no downstream targets or DNA binding motifs are applicable.
Upstream regulators (transcription factors regulating SOD1)
Total: 23 transcription factors
| TF | Regulation | Confidence | Evidence sources |
|---|---|---|---|
| SP1 | Activation | High | ChIP-seq (SIGNOR), curated databases (NTNU, TRRUST), predicted (DoRothEA_A, ExTRI), TF binding sites (TFactS, HTRI) |
| EGR1 | Activation | High | Literature-curated (TRRUST, TFactS), ChIP-seq (SIGNOR), regulatory DB (GEREDB), predicted (DoRothEA_A, ExTRI) |
| PPARG | Activation | High | Experimentally validated (ExTRI), regulatory DB (GEREDB), curated (NTNU) |
| MTF1 | Activation | - | Literature-curated (TRRUST), ChIP-seq (SIGNOR), regulatory DB (GEREDB) |
| NFE2L2 | Activation | Low | Literature-curated (TRRUST), ChIP-seq (SIGNOR), experimentally validated (ExTRI) |
| BTG2 | Activation | - | ChIP-seq (SIGNOR) |
| CEBPA | Unknown | High | Experimentally validated (ExTRI), curated (NTNU), predicted (DoRothEA_A) |
| ELK1 | Unknown | High | TF binding sites (TFactS), curated (NTNU), predicted (DoRothEA_A, ExTRI) |
| PPARD | - | - | Regulatory databases |
| NFKB | - | High | Experimentally validated (ExTRI) |
| FOXO3 | - | Low | Experimentally validated (ExTRI) |
| CEBPB | - | - | Regulatory databases |
| CEBPD | - | - | Regulatory databases |
| CEBPG | - | - | Regulatory databases |
| KLF4 | - | - | Regulatory databases |
| JUN | - | - | Regulatory databases |
| AHR | - | - | Regulatory databases |
| AP1 | - | - | Regulatory databases |
| MSX2 | - | - | Regulatory databases |
| TFAP2A | - | - | Regulatory databases |
| WT1 | - | - | Regulatory databases |
| YY1 | - | - | Regulatory databases |
| NFKBIA | - | - | Regulatory databases |
Evidence sources include curated databases (SIGNOR, TRRUST, NTNU Curated, GEREDB), predicted high-confidence interactions (DoRothEA_A), experimentally validated interactions (ExTRI), and transcription factor binding site predictions (TFactS, HTRI).
Based on my biobtree search, here’s the pharmacology data for SOD1:
Drug & pharmacology data
SOD1 is a confirmed drug target. The human superoxide dismutase 1 (SOD1) gene is recognized as a pharmacological target in ChEMBL and PharmGKB.
Targeting Molecules
Total count: 28 molecules in ChEMBL targeting SOD1 (CHEMBL2354)
Approved drug: 1
- Tofersen (Qalsody) | CHEMBL3833346 | Mechanism: SOD1 mRNA antisense oligonucleotide | Highest phase: 4 (FDA approved) | Alternative names: BIIB067, ISIS-SOD1Rx | Indication: Amyotrophic lateral sclerosis (ALS)
Research compounds: 27 additional molecules (mostly in phase 0/preclinical) including benzophthalazine derivatives and other small molecule inhibitors
Clinical Trials
Top 8 trials involving tofersen (SOD1-targeting drug):
- NCT02623699 | Phase 3 | Completed | Efficacy, safety, tolerability, PK/PD study in adults with inherited SOD1-ALS
- NCT03070119 | Phase 3 | Completed | Long-term evaluation of tofersen
- NCT04856982 | Phase 3 | Active, not recruiting | Study in clinically presymptomatic adults with SOD1 mutation
- NCT07223723 | Phase 4 | Recruiting | Long-term safety in Chinese participants with SOD1-ALS
- NCT07294144 | Phase 2 | Recruiting | Tofersen in non-SOD1 ALS (mechanism expansion study)
- NCT03764488 | Phase 1 | Completed | Microdose radiolabeled distribution study in healthy adults
- NCT04972487 | Expanded Access | Approved for marketing | Expanded access program for SOD1-ALS patients
- NCT07259980 | Observational | Not yet recruiting | Long-term safety observational study in SOD1-ALS
Pharmacogenomics
- PharmGKB status: SOD1 is a VIP (Very Important Pharmacogene) with variant annotations
- Known gene-drug interactions: SOD1 variants associated with familial ALS (fALS) affect drug response to tofersen; presymptomatic SOD1 mutation carriers are now eligible for treatment
- Dosing: Tofersen is administered as 120 mg intrathecal injection once monthly; no pharmacogenomic-driven dosing adjustments required, but genetic testing for SOD1 mutations is essential for patient eligibility
Expression profiles
Tissue Expression
| Rank | Tissue | Expression Score | Quality |
|---|---|---|---|
| 1 | Pons | 99.89 | Gold |
| 2 | Dorsal root ganglion | 99.81 | Gold |
| 3 | Substantia nigra pars compacta | 99.81 | Gold |
| 4 | Lateral nuclear group of thalamus | 99.78 | Gold |
| 5 | Superior vestibular nucleus | 99.78 | Gold |
| 6 | Substantia nigra pars reticulata | 99.78 | Gold |
| 7 | Right lobe of liver | 99.71 | Gold |
| 8 | Brodmann area 10 | 99.70 | Gold |
| 9 | Right adrenal gland cortex | 99.69 | Gold |
| 10 | Hypothalamus | 99.68 | Gold |
| 11 | Right adrenal gland | 99.68 | Gold |
| 12 | Brodmann area 9 | 99.67 | Gold |
| 13 | Dorsolateral prefrontal cortex | 99.67 | Gold |
| 14 | Frontal pole | 99.67 | Gold |
| 15 | Renal medulla | 99.66 | Gold |
| 16 | Adrenal cortex | 99.66 | Gold |
| 17 | Left adrenal gland | 99.66 | Gold |
| 18 | Bronchial epithelial cell | 99.65 | Gold |
| 19 | Left adrenal gland cortex | 99.64 | Gold |
| 20 | Trigeminal ganglion | 99.64 | Gold |
| 21 | Caudate nucleus | 99.64 | Gold |
| 22 | Anterior cingulate cortex | 99.63 | Gold |
| 23 | Cingulate cortex | 99.63 | Gold |
| 24 | Right frontal lobe | 99.62 | Gold |
| 25 | Nucleus accumbens | 99.62 | Gold |
| 26 | Midbrain | 99.62 | Gold |
| 27 | Prefrontal cortex | 99.61 | Gold |
| 28 | Epithelium of bronchus | 99.61 | Gold |
| 29 | Ventral tegmental area | 99.61 | Gold |
| 30 | Lateral globus pallidus | 99.61 | Gold |
Pattern: Ubiquitous expression across all tissues (304/305 conditions positive). Highest expression in nervous system tissues (brainstem nuclei, ganglia, cortical regions) and adrenal cortex. CNS predominance reflects SOD1’s critical antioxidant role in metabolically active neuronal populations. Average expression score across all tissues: 98.64 (maximum 99.89).
Cell Type Expression
Limited cell type data available in Bgee:
- Bronchial epithelial cell: 99.65 (Gold quality)
Single-Cell RNA-Seq Datasets
| Dataset | Tissue/System | Cell Count | Dataset ID |
|---|---|---|---|
| Emergent hematopoiesis | Fetal bone marrow | 56,592 | E-CURD-112 |
| Immune landscape | Head and neck cancer | 204,315 | E-GEOD-139324 |
| COVID-19 immunology | PBMCs/respiratory | 166,852 | E-GEOD-149689 |
| Glioblastoma infiltration | Glioblastoma tumor | 87,767 | E-CURD-95 |
| Endometrial organoids | Endometrium | 574,689 | E-MTAB-10283 |
| Hepatic immune cells | Liver | 79,612 | E-HCAD-9 |
| Biliary system | Biliary tract | 160,459 | E-MTAB-8495 |
| Placental cells | First-trimester placenta | 41,132 | E-HCAD-23 |
| Liver single-cell | Liver | 24,355 | E-MTAB-10553 |
| Immune cells (colon) | Colon lamina propria | 1,526 | E-CURD-89 |
| Ovarian cancer | Ovarian cancer models | 20,982 | E-MTAB-8559 |
| Dengue infection | PBMCs | 55,600 | E-MTAB-9467 |
| Breast cancer subtypes | Breast cancer/lymph node | 549 | E-GEOD-75688 |
| Glioblastoma cells | Glioblastoma | 62,867 | E-MTAB-9435 |
| T helper cells | T cells | 78,686 | E-HCAD-29 |
| Monocyte context | Whole blood/immune | 175,040 | E-MTAB-8207 |
| GvHD T lymphocytes | T lymphocytes | 19,075 | E-MTAB-8911 |
Notable patterns: SOD1 expression detected across diverse cell types and tissues in single-cell studies. Strong representation in immune cells (hematopoietic cells, T cells, monocytes), cancer samples, and inflammatory contexts (COVID-19, GvHD), consistent with its protective antioxidant role in reactive oxygen species (ROS) management during immune activation.
Disease associations
Mendelian/Monogenic Disease
| Disease | OMIM | Mondo | Orphanet | Inheritance | Evidence |
|---|---|---|---|---|---|
| Amyotrophic lateral sclerosis type 1 (ALS1) | 105400 | MONDO:0007103 | 803 | Autosomal dominant; Autosomal recessive | Strong |
| Spastic tetraplegia and axial hypotonia, progressive | 618598 | MONDO:0032828 | - | Autosomal recessive | Limited/Strong |
| Amyotrophic lateral sclerosis (general) | - | MONDO:0004976 | 803 | - | Supportive |
| Frontotemporal dementia with motor neuron disease | - | - | 275872 | - | - |
| Motor neuron disorder | - | MONDO:0020128 | 98503 | - | - |
| Amyotrophic lateral sclerosis type 10 | - | MONDO:0012790 | - | - | - |
Phenotype Associations (Top 30 HPO Terms)
- HP:0000006 – Autosomal dominant inheritance
- HP:0000007 – Autosomal recessive inheritance
- HP:0000217 – Xerostomia
- HP:0000358 – Posteriorly rotated ears
- HP:0000369 – Low-set ears
- HP:0000708 – Atypical behavior
- HP:0000712 – Emotional lability
- HP:0000716 – Depression
- HP:0000739 – Anxiety
- HP:0001251 – Ataxia
- HP:0001257 – Spasticity
- HP:0001260 – Dysarthria
- HP:0001272 – Cerebellar atrophy
- HP:0001276 – Hypertonia
- HP:0001285 – Spastic tetraparesis
- HP:0001308 – Tongue fasciculations
- HP:0001324 – Muscle weakness
- HP:0001344 – Absent speech
- HP:0001347 – Hyperreflexia
- HP:0001561 – Polyhydramnios
- HP:0001618 – Dysphonia
- HP:0001824 – Weight loss
- HP:0001845 – Overlapping toe
- HP:0002015 – Dysphagia
- HP:0002061 – Lower limb spasticity
- HP:0002094 – Dyspnea
- HP:0002145 – Frontotemporal dementia
- HP:0002151 – Increased circulating lactate concentration
- HP:0002180 – Neurodegeneration
- HP:0002267 – Exaggerated startle response
Complex Disease/GWAS Associations
| Trait/Disease | Mapped Gene | Chromosome | P-value |
|---|---|---|---|
| Amyotrophic lateral sclerosis | TIAM1 | 21 | 3.0 × 10⁻⁸ |