SOD1

Summary

SOD1 (superoxide dismutase 1, HGNC:11179) is a protein-coding gene on chromosome 21q22.11, encoding Superoxide dismutase [Cu-Zn] (P00441). Destroys radicals which are normally produced within the cells and which are toxic to biological systems. It is a common-essential gene (DepMap: required in 97.6% of cancer cell lines).

The 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.

Source: NCBI Gene 6647 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis type 1 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 299 total — 46 pathogenic, 48 likely-pathogenic
• Phenotypes (HPO): 72
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 97.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_000454

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11179
Approved symbol	SOD1
Name	superoxide dismutase 1
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Aliases	IPOA
Ensembl gene	ENSG00000142168
Ensembl biotype	protein_coding
OMIM	147450
Entrez	6647

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000270142, ENST00000389995, ENST00000470944, ENST00000476106, ENST00000877328, ENST00000877329, ENST00000877330, ENST00000877331, ENST00000877332, ENST00000928717, ENST00000928718, ENST00000928719, ENST00000928720, ENST00000928721

RefSeq mRNA: 1 — MANE Select: NM_000454 NM_000454

CCDS: CCDS33536

Canonical transcript exons

ENST00000270142 — 5 exons

Exon	Start	End
ENSE00001507447	31659693	31659841
ENSE00003492976	31663790	31663886
ENSE00003555033	31667258	31667375
ENSE00003624439	31666449	31666518
ENSE00003902052	31668471	31668931

Expression profiles

Bgee: expression breadth ubiquitous, 304 present calls, max score 99.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 382.4666 / max 4528.7049, expressed in 1828 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188789	382.4666	1828

Top tissues by expression

305 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	99.89	gold quality
dorsal root ganglion	UBERON:0000044	99.81	gold quality
substantia nigra pars compacta	UBERON:0001965	99.81	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.78	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.78	gold quality
superior vestibular nucleus	UBERON:0007227	99.78	gold quality
right lobe of liver	UBERON:0001114	99.71	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.70	gold quality
right adrenal gland cortex	UBERON:0035827	99.69	gold quality
right adrenal gland	UBERON:0001233	99.68	gold quality
hypothalamus	UBERON:0001898	99.68	gold quality
frontal pole	UBERON:0002795	99.67	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.67	gold quality
renal medulla	UBERON:0000362	99.66	gold quality
left adrenal gland	UBERON:0001234	99.66	gold quality
adrenal cortex	UBERON:0001235	99.66	gold quality
bronchial epithelial cell	CL:0002328	99.65	gold quality
trigeminal ganglion	UBERON:0001675	99.64	gold quality
caudate nucleus	UBERON:0001873	99.64	gold quality
left adrenal gland cortex	UBERON:0035825	99.64	gold quality
cingulate cortex	UBERON:0003027	99.63	gold quality
anterior cingulate cortex	UBERON:0009835	99.63	gold quality
nucleus accumbens	UBERON:0001882	99.62	gold quality
midbrain	UBERON:0001891	99.62	gold quality
right frontal lobe	UBERON:0002810	99.62	gold quality
prefrontal cortex	UBERON:0000451	99.61	gold quality
epithelium of bronchus	UBERON:0002031	99.61	gold quality
substantia nigra	UBERON:0002038	99.61	gold quality
lateral globus pallidus	UBERON:0002476	99.61	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-7407	yes	3892.22
E-HCAD-25	yes	3092.33
E-HCAD-9	yes	2798.66
E-MTAB-8495	yes	2428.32
E-GEOD-134144	yes	1810.79
E-CURD-122	yes	43.53
E-MTAB-10553	yes	41.31
E-CURD-88	yes	33.01
E-HCAD-11	yes	21.71
E-MTAB-8142	yes	17.41
E-MTAB-7316	yes	12.37
E-MTAB-10596	no	1004.05
E-MTAB-11011	no	336.42
E-HCAD-4	no	55.87
E-CURD-120	no	46.16

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, BTG2, CEBPA, CEBPB, CEBPD, CEBPG, EGR1, ELK1, FOXO3, JUN, KLF4, MSX2, MTF1, NFE2L2, NFKB, NFKBIA, PPARD, PPARG, SP1, TFAP2A, WT1, YY1

miRNA regulators (miRDB)

26 targeting SOD1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-6877-3P	98.98	65.83	560
HSA-MIR-6819-3P	98.95	65.57	572
HSA-MIR-4275	97.96	68.42	1549
HSA-MIR-4714-5P	97.04	67.76	955
HSA-MIR-621	96.76	66.89	371
HSA-MIR-552-3P	96.68	64.12	1026
HSA-MIR-1245A	96.33	66.25	498
HSA-MIR-8079	96.33	66.11	484
HSA-MIR-6823-5P	96.26	65.69	919

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• This study searched for the D90A CuZn-SOD mutation in different ethnic populations of the Russian Federation and found it in locations close to the Scandinavian peninsula and in remote populations in Asia, making this mutation the most common globally. (PMID:11675874)
• Cu,Zn-SOD and Mn-SOD are differently regulated by estrogen and progesterone in human endometrial stromal cells (PMID:11756571)
• Antioxidant proteins in fetal brain: superoxide dismutase-1 (SOD-1) protein is not overexpressed in fetal Down syndrome. (PMID:11771762)
• mutant superoxide dismutases associated with familial amyotrophic lateral sclerosis (PMID:11854284)
• 14 different variants of human copper/zinc superoxide dismutase (SOD1) associated with familial amyotrophic lateral sclerosis (PMID:11854285)
• Transcriptional regulation and environmental induction of gene encoding copper- and zinc-containing superoxide dismutase. (PMID:11912919)
• Homocysteine (HC) mediates oxidative cytotoxicity in cultured motor neurons by toxic gain of function of mutant SOD1 (A4V) indicating that motor neurons containing mutant SOD1 may be more susceptible to physiological concentrations of HC. (PMID:11930144)
• Early onset of severe familial amyotrophic lateral sclerosis with a SOD-1 mutation: potential impact of CNTF as a candidate modifier gene. (PMID:11951178)
• mutations of the gene have been linked to familial amyotrophic lateral sclerosis - review (PMID:11996514)
• Identification of a novel mutation in Cu/Zn superoxide dismutase gene associated with familial amyotrophic lateral sclerosis. missense mutation (Ala140Gly) in exon 5 (PMID:12039658)
• causes dysfunction of oxidative phosphorylation in mitochondria of transgenic mice (PMID:12050154)
• Effect of Cu,Zn superoxide dismutase on cholesterol metabolism in human hepatocarcinoma (HepG2) cells (PMID:12099681)
• Transgenic mice expressing human SOD1 with ALS-linked mutations at 2 of the 4 His residues crucial for coordinated copper binding (H46R/H48Q develop motor neuron disease with fibrillar inclusions like mice with G37R, G58R, and G93A variants. (PMID:12127151)
• causative genes for familial amyotrophic lateral sclerosis (PMID:12138710)
• antioxidant effects of human CuZn-SOD reduce cellular edema due to oxidative stress during reperfusion but not during ischemia after 1 h middle cerebral artery occlusion (PMID:12144846)
• SOD1 mutants are recognized by Dorfin protein and targeted for proteasomal degradation (PMID:12145308)
• genetic heterogeneity of patients with ALS harboring mutations in the SOD1 gene (PMID:12210393)
• The combination of Hsp70 abd Hsp40 reduced intracytoplasmic aggregates and improved neurite outgrowth, and were upregulated in cells expressing mutant SOD1. (PMID:12213295)
• SOD1 D76V mutation identified in four family members predicts a long survival and shows genotype-phenotype correlation. (PMID:12215228)
• The role of superoxide dismutase in human diseases is discussed [review] (PMID:12218958)
• Erythrocyte analyses of CuZn-superoxide dismutase in D90A heterozygotes find no evidence that the putative protective factor in recessive families acts by downregulating the synthesis or altering the molecular structure or turnover of the mutant enzyme. (PMID:12270693)
• Oxidation of select histidine residues that bind metals in the active site mediates SOD1 aggregation (PMID:12356748)
• Mitochondrial localization of mutant enzyme triggers caspase-dependent cell death in a cellular model of familial amyotrophic lateral sclerosis (PMID:12393885)
• This mutation (H80A) is believed to alter zinc ligand binding, and its functional significance correlates well with the aggressive clinical course and postmortem findings. (PMID:12402272)
• Sustained expression of mutant SOD1 leads to proteasomal inhibition and motor neuronal death, which in part explains the pathogenesis of mutant SOD1-linked ALS (PMID:12437574)
• identifed and characterized key stability and structural differences resulting from the A4V mutation; architectural destabilization of the HSOD protein may underlie the toxic function of HSOD familial amyotrophic lateral sclerosis mutations (PMID:12441104)
• Authors propose that a cis-acting regulatory polymorphism has arisen close to D90A-SOD1 in the recessive founder, which decreases ALS susceptibility in heterozygotes and slows disease progression. (PMID:12442272)
• Malignsant lung tumors (squamous cell carcinoma and adenocarcinoma) had significantly decreased levels of this enzyme. (PMID:12447480)
• Mutants of this enzyme in amyotrophic lateral sclerosis are susceptible to disulfide reduction. (PMID:12458194)
• The cytosolic proteome in a cell culture model of familial amyotrophic lateral sclerosis reveals alterations to the proteasome, antioxidant defenses, nitric oxide synthetic pathways and mutations in this enzyme. (PMID:12475980)
• There is a novel mutation in this gene in a Korean family with amyotrophic lateral sclerosis. (PMID:12480087)
• Expression is implicated in placenta development. (PMID:12485882)
• Phenotypic effects of familial amyotrophic lateral sclerosis mutant alleles in transgsenic Drosophila (PMID:12502789)
• Data show that overexpression of wild-type superoxide dismutase 1 in cells expressing mutant forms of the enzyme significantly enhanced cell survival and reduced apoptosis after serum deprivation. (PMID:12531528)
• Cu-Zn superoxide dismutase is exported by microvesicular granules (PMID:12573532)
• The large number of Cu/Zn SOD-related ALS mutations at residue 93 indicates that the loss of the glycine and not the addition of an alanine is an important factor in the pathology arising from G93A Cu/Zn SOD. (PMID:12590575)
• Erythrocyte SOD activity and glutathione system are altered in men with new diagnosed BD. These alterations may be contributory factor for tissue damage associated with BD. (PMID:12597246)
• results suggest that high glucose flux through aldose reductase inhibits the expression of catalase, CuZn superoxide-dismutase and glutathione peroxidase (PMID:12606529)
• Overexpression of SOD1 increases release of TNF-alpha, VEGF, and metalloproteinases MMP-2 and MMP-9 from cultured, activated peritoneal macrophages, and increases TNF-alpha levels in the serum, as well as the delayed-type hypersensitivity response. (PMID:12626552)
• This review is a critical survey of in vitro characteristics of over 30 of the 90 different CuZnSOD mutant proteins known to cause familial amyotrophic lateral sclerosis, in order to determine the differences between mutant and wild-type properties. (PMID:12644909)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sod1	ENSDARG00000043848
mus_musculus	Sod1	ENSMUSG00000022982
rattus_norvegicus	Sod1	ENSRNOG00000002115
drosophila_melanogaster	Sod1	FBGN0003462
caenorhabditis_elegans		WBGENE00004933

Paralogs (2): SOD3 (ENSG00000109610), CCS (ENSG00000173992)

Protein

Protein identifiers

Superoxide dismutase [Cu-Zn] — P00441 (reviewed: P00441)

Alternative names: Hydrogen sulfide oxidase, Superoxide dismutase 1

All UniProt accessions (3): P00441, H7BYH4, V9HWC9

UniProt curated annotations — full annotation on UniProt →

Function. Destroys radicals which are normally produced within the cells and which are toxic to biological systems. Catalyzes the oxidation of hydrogen sulfide (H2S) to sulfate, playing an important role in detoxifying H2S and limiting the accumulation of reactive sulfur species (RSS) such as persulfides and polysulfides.

Subunit / interactions. Homodimer; non-disulfide-linked. Homodimerization may take place via the ditryptophan cross-link at Trp-33. Heterodimer with SOD1. The heterodimer CCS:SOD1 interacts with SLC31A1; this heterotrimer is Cu(1+)-mediated and its maintenance is regulated through SOD1 activation. Interacts with DAOA; the interaction is direct.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Unlike wild-type protein, the pathogenic variants ALS1 Arg-38, Arg-47, Arg-86 and Ala-94 are polyubiquitinated by RNF19A leading to their proteasomal degradation. The pathogenic variants ALS1 Arg-86 and Ala-94 are ubiquitinated by MARCH5 leading to their proteasomal degradation. The ditryptophan cross-link at Trp-33 is responsible for the non-disulfide-linked homodimerization. Such modification might only occur in extreme conditions and additional experimental evidence is required. Palmitoylation helps nuclear targeting and decreases catalytic activity. Succinylation, adjacent to copper catalytic site, probably inhibits activity. Desuccinylation by SIRT5 enhances activity.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. Spastic tetraplegia and axial hypotonia, progressive (STAHP) [MIM:618598] An autosomal recessive, neurologic disorder characterized by loss of motor abilities in the first year of life, after which severe, progressive spastic tetraparesis develops. Affected individuals have severe axial hypotonia, hyperekplexia, hypertonia, and myokymia, reflecting upper motor neuron involvement. Cognitive development may be affected. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 copper ion per subunit. Binds 1 zinc ion per subunit.

Miscellaneous. The protein (both wild-type and ALS1 variants) has a tendency to form fibrillar aggregates in the absence of the intramolecular disulfide bond or of bound zinc ions. These aggregates may have cytotoxic effects. Zinc binding promotes dimerization and stabilizes the native form.

Similarity. Belongs to the Cu-Zn superoxide dismutase family.

RefSeq proteins (1): NP_000445* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00080

Enzyme classification (BRENDA):

• EC 1.15.1.1 — superoxide dismutase (BRENDA: 258 organisms, 98 substrates, 359 inhibitors, 19 Km, 7 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NITRO BLUE TETRAZOLIUM	0.025–15	2
RIBOFLAVIN	0.0016–2.3	2
SUPEROXIDE	0.0115–0.046	2
O2-	0.355	1
O2.-	—	0

Catalyzed reactions (Rhea), 2 shown:

• 2 superoxide + 2 H(+) = H2O2 + O2 (RHEA:20696)
• hydrogen sulfide + 2 O2 = sulfate + H(+) (RHEA:85007)

UniProt features (149 total): sequence variant 81, strand 22, mutagenesis site 14, modified residue 12, binding site 8, helix 4, sequence conflict 2, initiator methionine 1, chain 1, turn 1, lipid moiety-binding region 1, disulfide bond 1, cross-link 1

Structure

Experimental structures (PDB)

156 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4A7U	X-RAY DIFFRACTION	0.98
2WYT	X-RAY DIFFRACTION	1
4A7V	X-RAY DIFFRACTION	1
1MFM	X-RAY DIFFRACTION	1.02
4A7S	X-RAY DIFFRACTION	1.06
2C9V	X-RAY DIFFRACTION	1.07
2V0A	X-RAY DIFFRACTION	1.15
4A7Q	X-RAY DIFFRACTION	1.22
2C9S	X-RAY DIFFRACTION	1.24
2C9U	X-RAY DIFFRACTION	1.24
4A7G	X-RAY DIFFRACTION	1.24
5J0F	X-RAY DIFFRACTION	1.25
6Z3V	X-RAY DIFFRACTION	1.25
4BCY	X-RAY DIFFRACTION	1.27
1OZU	X-RAY DIFFRACTION	1.3
2VR6	X-RAY DIFFRACTION	1.3
4NIO	X-RAY DIFFRACTION	1.3
5O3Y	X-RAY DIFFRACTION	1.3
7T8G	X-RAY DIFFRACTION	1.35
2VR8	X-RAY DIFFRACTION	1.36
1P1V	X-RAY DIFFRACTION	1.4
5WMJ	X-RAY DIFFRACTION	1.4
6Z4O	X-RAY DIFFRACTION	1.4
7T8E	X-RAY DIFFRACTION	1.4
7T8F	X-RAY DIFFRACTION	1.4
3GZQ	X-RAY DIFFRACTION	1.4
4NIN	X-RAY DIFFRACTION	1.4
2XJK	X-RAY DIFFRACTION	1.45
4A7T	X-RAY DIFFRACTION	1.45
6Z4G	X-RAY DIFFRACTION	1.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00441-F1	97.95	0.98

Antibody-complex structures (SAbDab): 6 — 7NXX, 8K33, 8K3A, 8K3L, 8YAF, 8YAT

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 47; 49; 64; 64; 72; 81; 84; 121

Post-translational modifications (14): 2, 4, 10, 92, 99, 103, 106, 108, 123, 123, 137, 137, 7, 33

Disulfide bonds (1): 58–147

Mutagenesis-validated functional residues (14):

Position	Phenotype
7	no palmitoylation, reduced nuclear targeting. enhances formation of fibrillar aggregates in the absence of bound zinc; w
51–52	abolishes dimerization; when associated with q-134.
58	exhibits very slow copper acquisition.
58	enhances formation of fibrillar aggregates in the absence of bound zinc; when associated with s-7; s-112 and s-147.
81	loss of zinc binding and enhanced tendency to form aggregates; when associated with a-84.
81	destabilization of dimer and loss of zinc binding; when associated with s-84.
84	loss of zinc binding and enhanced tendency to form aggregates; when associated with a-81.
84	destabilization of dimer and loss of zinc binding; when associated with s-81.
112	enhances formation of fibrillar aggregates in the absence of bound zinc; when associated with s-7; s-58 and s-147.
123	decreased succinylation.
123	mimicks constitutive succinylation state; decreased activity.
134	abolishes dimerization; when associated with e-50 and e-51.
147	exhibits very slow copper acquisition.
147	enhances formation of fibrillar aggregates in the absence of bound zinc; when associated with s-7; s-58 and s-112.

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
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
R-HSA-109582	Hemostasis
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-2262752	Cellular responses to stress
R-HSA-447115	Interleukin-12 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9020591	Interleukin-12 signaling
R-HSA-9711123	Cellular response to chemical stress

MSigDB gene sets: 673 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, MORF_MTA1, GOBP_REGULATION_OF_CELL_ACTIVATION, MODULE_93, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_BEHAVIOR, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_BLOOD_PRESSURE

GO Biological Process (66): response to superoxide (GO:0000303), ovarian follicle development (GO:0001541), positive regulation of cytokine production (GO:0001819), placenta development (GO:0001890), retina homeostasis (GO:0001895), response to amphetamine (GO:0001975), myeloid cell homeostasis (GO:0002262), glutathione metabolic process (GO:0006749), superoxide metabolic process (GO:0006801), intracellular iron ion homeostasis (GO:0006879), apoptotic process (GO:0006915), spermatogenesis (GO:0007283), embryo implantation (GO:0007566), sensory perception of sound (GO:0007605), locomotory behavior (GO:0007626), anterograde axonal transport (GO:0008089), retrograde axonal transport (GO:0008090), regulation of blood pressure (GO:0008217), determination of adult lifespan (GO:0008340), response to heat (GO:0009408), response to xenobiotic stimulus (GO:0009410), gene expression (GO:0010467), transmission of nerve impulse (GO:0019226), neuronal action potential (GO:0019228), removal of superoxide radicals (GO:0019430), response to nutrient levels (GO:0031667), peripheral nervous system myelin maintenance (GO:0032287), positive regulation of superoxide anion generation (GO:0032930), regulation of T cell differentiation in thymus (GO:0033081), response to carbon monoxide (GO:0034465), ectopic germ cell programmed cell death (GO:0035234), cellular response to potassium ion (GO:0035865), regulation of multicellular organism growth (GO:0040014), response to hydrogen peroxide (GO:0042542), superoxide anion generation (GO:0042554), positive regulation of apoptotic process (GO:0043065), regulation of GTPase activity (GO:0043087), positive regulation of MAPK cascade (GO:0043410), negative regulation of neuron apoptotic process (GO:0043524), response to ethanol (GO:0045471)

GO Molecular Function (13): superoxide dismutase activity (GO:0004784), copper ion binding (GO:0005507), zinc ion binding (GO:0008270), protein phosphatase 2B binding (GO:0030346), small GTPase binding (GO:0031267), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515), antioxidant activity (GO:0016209), oxidoreductase activity (GO:0016491), enzyme binding (GO:0019899), metal ion binding (GO:0046872)

GO Cellular Component (20): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial intermembrane space (GO:0005758), mitochondrial matrix (GO:0005759), lysosome (GO:0005764), peroxisome (GO:0005777), cytosol (GO:0005829), dense core granule (GO:0031045), cytoplasmic vesicle (GO:0031410), dendrite cytoplasm (GO:0032839), protein-containing complex (GO:0032991), neuronal cell body (GO:0043025), extracellular exosome (GO:0070062), axon cytoplasm (GO:1904115), plasma membrane (GO:0005886), secretory granule (GO:0030141)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Cellular response to chemical stress	1
Interleukin-12 signaling	1
Immune System	1
Cellular responses to stimuli	1
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1
Hemostasis	1
Platelet activation, signaling and aggregation	1
Interleukin-12 family signaling	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein binding	3
cytoplasm	3
axonal transport	2
axon cytoplasm	2
transition metal ion binding	2
intracellular membrane-bounded organelle	2
neuron projection cytoplasm	2
response to oxygen radical	1
female gonad development	1
anatomical structure development	1
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
animal organ development	1
tissue homeostasis	1
response to amine	1
immune system process	1
homeostasis of number of cells	1
modified amino acid metabolic process	1
sulfur compound metabolic process	1
reactive oxygen species metabolic process	1
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
developmental process involved in reproduction	1
male gamete generation	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
sensory perception of mechanical stimulus	1
behavior	1
blood circulation	1
regulation of biological quality	1
multicellular organismal process	1
response to stress	1
response to temperature stimulus	1

Protein interactions and networks

STRING

5892 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SOD1	FUS	P35637	992
SOD1	TARDBP	Q13148	989
SOD1	BCL2	P10415	977
SOD1	VDAC1	P21796	951
SOD1	A0A087WTZ4	A0A087WTZ4	926
SOD1	ATOX1	O00244	915
SOD1	C9orf72	Q96LT7	898
SOD1	ALS2	Q96Q42	888
SOD1	HSPA4	P34932	887
SOD1	SQSTM1	Q13501	884
SOD1	OPTN	Q96CV9	872
SOD1	CYBB	P04839	869
SOD1	SNCA	P37840	860
SOD1	HTT	P42858	845
SOD1	UBQLN2	Q9UHD9	845

IntAct

359 interactions, top by confidence:

A	B	Type	Score
SOD1	SOD1	psi-mi:“MI:0407”(direct interaction)	0.980
CCS	SOD1	psi-mi:“MI:0915”(physical association)	0.830
SOD1	CCS	psi-mi:“MI:0914”(association)	0.830
CCS	SOD1	psi-mi:“MI:0914”(association)	0.830
SOD1	Hspa5	psi-mi:“MI:0915”(physical association)	0.690
SOD1	Hspa5	psi-mi:“MI:0407”(direct interaction)	0.690
SOD1	PSMC1	psi-mi:“MI:0915”(physical association)	0.670
SOD1	PRDX5	psi-mi:“MI:0915”(physical association)	0.610
BCL2L13	SOD1	psi-mi:“MI:0915”(physical association)	0.590

BioGRID (556): SOD1 (Affinity Capture-Western), ACY1 (Co-fractionation), ADK (Co-fractionation), ADSL (Co-fractionation), AK2 (Co-fractionation), AKR1A1 (Co-fractionation), AKR1B1 (Co-fractionation), AKR1B15 (Co-fractionation), LOC101930400 (Co-fractionation), AKR1C2 (Co-fractionation), ASNS (Co-fractionation), ATOX1 (Co-fractionation), C11orf54 (Co-fractionation), CAT (Co-fractionation), CCS (Co-fractionation)

ESM2 similar proteins: B0BNN3, O76206, P00441, P00445, P00915, P00916, P00917, P00918, P00919, P00920, P00921, P00922, P07450, P07451, P07452, P07630, P13634, P14141, P16015, P27139, P28755, P35217, P43166, P48282, P48284, P60052, P82205, P83299, Q0IIW3, Q1LZA1, Q27504, Q3SZX4, Q42961, Q5S1S4, Q6C662, Q7M316, Q7M317, Q8HXQ0, Q8HXQ1, Q8HXQ2

Diamond homologs: A0A1D1VU85, A2XGP6, C0HK70, H6BDU4, J9VLJ9, O04996, O04997, O12933, O14618, O22668, O46412, O49044, O49073, O65174, O65175, O65198, O65199, O65768, O73872, O78310, P00441, P00442, P00443, P04178, P07505, P07632, P08228, P09212, P09670, P09678, P10791, P10792, P11418, P11428, P11964, P13926, P14830, P14831, P15107, P22233

SIGNOR signaling

33 interactions.

A	Effect	B	Mechanism
CEBPD	“up-regulates quantity by expression”	SOD1	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	SOD1	“transcriptional regulation”
WT1	“up-regulates quantity by expression”	SOD1	“transcriptional regulation”
SP1	“up-regulates quantity by expression”	SOD1	“transcriptional regulation”
KLF4	“down-regulates quantity by repression”	SOD1	“transcriptional regulation”
MTF1	“up-regulates quantity by expression”	SOD1	“transcriptional regulation”
BTG2	“up-regulates quantity by expression”	SOD1	“transcriptional regulation”
NFE2L2	“up-regulates quantity by expression”	SOD1	“transcriptional regulation”
PPARD	“up-regulates quantity by expression”	SOD1	“transcriptional regulation”
SOD1	“up-regulates quantity”	Protein_aggregates
SOD1	“up-regulates quantity”	S100A4
SOD1	“down-regulates activity”	DERL1	binding
SOD1	“up-regulates activity”	BCL2	binding
SOD1	“down-regulates quantity”	superoxide	“chemical modification”
SOD1	“up-regulates quantity”	dioxygen	“chemical modification”
SOD1	“up-regulates quantity”	“hydrogen peroxide”	“chemical modification”
superoxide	“up-regulates activity”	SOD1	“precursor of”
MARCHF5	“down-regulates quantity”	SOD1	ubiquitination
SOD1	“up-regulates activity”	ERN1	binding
SOD1	“up-regulates activity”	EIF2AK3	binding
SOD1	up-regulates	“ER stress”
SOD1	up-regulates	MAP3K5
SOD1	up-regulates	Protein_aggregates
MIF	“down-regulates quantity by destabilization”	SOD1	relocalization
SOD1	“down-regulates activity”	VDAC1	binding
SQSTM1	“down-regulates quantity by destabilization”	SOD1	binding
DIP2A	“up-regulates activity”	SOD1	binding
CHEK2	“up-regulates activity”	SOD1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of activated PAK-2p34 by proteasome mediated degradation	5	26.8×	8e-05
Vpu mediated degradation of CD4	5	25.5×	8e-05
Autodegradation of the E3 ubiquitin ligase COP1	5	25.5×	8e-05
Ubiquitin-dependent degradation of Cyclin D	5	25.5×	8e-05
Cross-presentation of soluble exogenous antigens (endosomes)	5	24.4×	8e-05
Vif-mediated degradation of APOBEC3G	5	24.4×	8e-05
AUF1 (hnRNP D0) binds and destabilizes mRNA	5	23.9×	8e-05
Degradation of AXIN	5	23.9×	8e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

299 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	46
Likely pathogenic	48
Uncertain significance	77
Likely benign	51
Benign	17

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1066874	NM_000454.5(SOD1):c.304G>C (p.Asp102His)	Pathogenic
1072003	NM_000454.5(SOD1):c.281G>A (p.Gly94Asp)	Pathogenic
14752	NM_000454.5(SOD1):c.112G>A (p.Gly38Arg)	Pathogenic
14754	NM_000454.5(SOD1):c.124G>A (p.Gly42Ser)	Pathogenic
14755	NM_000454.5(SOD1):c.125G>A (p.Gly42Asp)	Pathogenic
14756	NM_000454.5(SOD1):c.131A>G (p.His44Arg)	Pathogenic
14757	NM_000454.5(SOD1):c.319C>G (p.Leu107Val)	Pathogenic
14758	NM_000454.5(SOD1):c.256G>C (p.Gly86Arg)	Pathogenic
14759	NM_000454.5(SOD1):c.280G>T (p.Gly94Cys)	Pathogenic
14760	NM_000454.5(SOD1):c.281G>C (p.Gly94Ala)	Pathogenic
14761	NM_000454.5(SOD1):c.302A>G (p.Glu101Gly)	Pathogenic
14762	NM_000454.5(SOD1):c.338T>C (p.Ile113Thr)	Pathogenic
14764	NM_000454.5(SOD1):c.140A>G (p.His47Arg)	Pathogenic
14765	NM_000454.5(SOD1):c.13G>A (p.Ala5Thr)	Pathogenic
14768	NM_000454.5(SOD1):c.434T>C (p.Leu145Ser)	Pathogenic
14769	NM_000454.5(SOD1):c.436G>A (p.Ala146Thr)	Pathogenic
14771	NM_000454.5(SOD1):c.20G>T (p.Cys7Phe)	Pathogenic
14772	NM_000454.5(SOD1):c.455T>C (p.Ile152Thr)	Pathogenic
14773	NM_000454.5(SOD1):c.64G>A (p.Glu22Lys)	Pathogenic
14774	NM_000454.5(SOD1):c.404G>A (p.Ser135Asn)	Pathogenic
14775	NM_000454.5(SOD1):c.253T>G (p.Leu85Val)	Pathogenic
14776	NM_000454.5(SOD1):c.49G>A (p.Gly17Ser)	Pathogenic
14777	NM_000454.5(SOD1):c.380T>A (p.Leu127Ter)	Pathogenic
14778	NM_000454.5(SOD1):c.358-11A>G	Pathogenic
14781	NM_000454.5(SOD1):c.137T>G (p.Phe46Cys)	Pathogenic
14782	NM_000454.5(SOD1):c.242A>G (p.His81Arg)	Pathogenic
14784	NM_000454.5(SOD1):c.280G>C (p.Gly94Arg)	Pathogenic
14786	NM_000454.5(SOD1):c.358-304=	Pathogenic
1500887	NM_000454.5(SOD1):c.19T>A (p.Cys7Ser)	Pathogenic
1802147	NM_000454.5(SOD1):c.272A>T (p.Asp91Val)	Pathogenic

SpliceAI

688 predictions. Top by Δscore:

Variant	Effect	Δscore
21:31666448:GGCT:G	acceptor_gain	1.0000
21:31667250:A:AG	acceptor_gain	1.0000
21:31667251:T:G	acceptor_gain	1.0000
21:31667253:A:AG	acceptor_gain	1.0000
21:31667253:ATTAG:A	acceptor_gain	1.0000
21:31667254:T:G	acceptor_gain	1.0000
21:31667254:TTAGG:T	acceptor_loss	1.0000
21:31667255:TAG:T	acceptor_loss	1.0000
21:31667256:A:AG	acceptor_gain	1.0000
21:31667256:AG:A	acceptor_gain	1.0000
21:31667257:G:GT	acceptor_gain	1.0000
21:31667257:GG:G	acceptor_gain	1.0000
21:31667257:GGC:G	acceptor_gain	1.0000
21:31667257:GGCA:G	acceptor_gain	1.0000
21:31667257:GGCAT:G	acceptor_gain	1.0000
21:31667371:TGGTG:T	donor_gain	1.0000
21:31667372:GGTGG:G	donor_gain	1.0000
21:31667373:GTG:G	donor_gain	1.0000
21:31667374:TG:T	donor_gain	1.0000
21:31667374:TGG:T	donor_loss	1.0000
21:31667375:GG:G	donor_gain	1.0000
21:31667376:G:GG	donor_gain	1.0000
21:31668468:CAGG:C	acceptor_loss	1.0000
21:31668469:A:AC	acceptor_loss	1.0000
21:31668469:A:AG	acceptor_gain	1.0000
21:31668470:G:GG	acceptor_gain	1.0000
21:31668470:GGTCC:G	acceptor_gain	1.0000
21:31660008:TGCCC:T	donor_gain	0.9900
21:31666444:A:G	acceptor_gain	0.9900
21:31666446:TA:T	acceptor_loss	0.9900

AlphaMissense

1008 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:31667365:G:C	R116P	0.996
21:31668529:G:A	G139E	0.996
21:31668529:G:T	G139V	0.996
21:31663856:C:G	H47D	0.995
21:31663862:C:G	H49D	0.995
21:31668486:G:C	D125H	0.995
21:31663851:G:A	G45E	0.994
21:31663860:T:A	V48D	0.994
21:31666469:C:G	H64D	0.994
21:31666471:C:A	H64Q	0.994
21:31666471:C:G	H64Q	0.994
21:31667364:C:A	R116S	0.994
21:31668472:T:A	V120D	0.994
21:31659790:C:G	C7W	0.993
21:31663862:C:A	H49N	0.993
21:31666495:C:A	H72Q	0.993
21:31666495:C:G	H72Q	0.993
21:31667266:G:A	G83E	0.993
21:31668487:A:T	D125V	0.993
21:31663872:G:A	G52E	0.992
21:31666493:C:G	H72D	0.992
21:31667266:G:T	G83V	0.992
21:31667279:T:A	N87K	0.992
21:31667279:T:G	N87K	0.992
21:31659818:G:C	G17R	0.991
21:31663847:C:G	H44D	0.991
21:31663856:C:A	H47N	0.991
21:31663858:T:A	H47Q	0.991
21:31663858:T:G	H47Q	0.991
21:31663864:T:A	H49Q	0.991

dbSNP variants (sampled 300 via entrez): RS1000042332 (21:31663072 T>G), RS1000108530 (21:31668243 T>C,G), RS1000379490 (21:31666392 A>G,T), RS1000430520 (21:31666113 A>G), RS1000994601 (21:31661395 G>A,C), RS1000996461 (21:31666910 A>G), RS1001102409 (21:31666564 A>G), RS1001341759 (21:31661032 G>A), RS1001545830 (21:31660219 C>G,T), RS1001643690 (21:31665717 T>G), RS1001891577 (21:31660436 A>G), RS1002006227 (21:31663638 G>A,C,T), RS1002055099 (21:31658544 T>C), RS1002107308 (21:31658846 G>C), RS1002717419 (21:31660617 T>C)

Disease associations

OMIM: gene MIM:147450 | disease phenotypes: MIM:105400, MIM:618598, MIM:612069

GenCC curated gene-disease

Disease	Classification	Inheritance
spastic tetraplegia and axial hypotonia, progressive	Strong	Autosomal recessive
amyotrophic lateral sclerosis type 1	Strong	Autosomal dominant
amyotrophic lateral sclerosis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
amyotrophic lateral sclerosis type 1	Definitive	AD

Mondo (5): amyotrophic lateral sclerosis type 1 (MONDO:0007103), spastic tetraplegia and axial hypotonia, progressive (MONDO:0032828), amyotrophic lateral sclerosis (MONDO:0004976), motor neuron disorder (MONDO:0020128), amyotrophic lateral sclerosis type 10 (MONDO:0012790)

Orphanet (3): Amyotrophic lateral sclerosis (Orphanet:803), Motor neuron disease (Orphanet:98503), Frontotemporal dementia with motor neuron disease (Orphanet:275872)

HPO phenotypes

72 total (30 of 72 shown, HPO-id order):

HPO	Term
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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000781_2	Amyotrophic lateral sclerosis	3.000000e-08

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050
D016472	Motor Neuron Disease	C10.574.562; C10.668.467
C567429	Amyotrophic Lateral Sclerosis 10 (supp.)
C531617	Amyotrophic lateral sclerosis 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2354 (SINGLE PROTEIN), CHEMBL4106171 (PROTEIN FAMILY)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs36232792	SOD1		0.00	0

ChEMBL bioactivities

18 potent at pChembl≥5 of 29 total, top 18 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.17	EC50	67	nM	CHEMBL1939222
6.77	EC50	170	nM	CHEMBL1643557
6.29	EC50	510	nM	CHEMBL2165611
6.24	EC50	580	nM	CHEMBL2165609
6.15	EC50	710	nM	CHEMBL1643556
6.14	EC50	720	nM	CHEMBL2165607
6.10	EC50	790	nM	CHEMBL2165605
6.06	EC50	870	nM	CHEMBL2165608
5.99	EC50	1020	nM	CHEMBL2165612
5.97	EC50	1070	nM	CHEMBL2165610
5.85	EC50	1410	nM	CHEMBL2165603
5.83	EC50	1470	nM	CHEMBL2165604
5.71	EC50	1960	nM	CHEMBL2165606
5.71	EC50	1930	nM	CHEMBL1643541
5.55	EC50	2840	nM	CHEMBL2165613
5.54	EC50	2880	nM	CHEMBL2165601
5.43	EC50	3700	nM	CHEMBL2165614
5.33	EC50	4700	nM	CHEMBL2165602

PubChem BioAssay actives

18 with measured affinity, of 133 total; 18 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[(3,5-dichlorophenoxy)methyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	0.0670	uM
5-[(3,5-dichlorophenyl)sulfanylmethyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	0.1700	uM
5-[(3,5-dibromophenoxy)methyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	0.5100	uM
5-[[3,5-bis(trifluoromethyl)phenoxy]methyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	0.5800	uM
5-[(2,6-dichlorophenyl)sulfanylmethyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	0.7100	uM
5-[(3-ethylphenoxy)methyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	0.7200	uM
5-[(4-chlorophenoxy)methyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	0.7900	uM
5-[(3-tert-butylphenoxy)methyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	0.8700	uM
5-[(3-bromophenoxy)methyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	1.0200	uM
5-[(3,5-difluorophenoxy)methyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	1.0700	uM
5-[(3,5-dichlorophenyl)sulfonylmethyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	1.4100	uM
5-[(4-chloro-2,5-dimethylphenyl)sulfonylmethyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	1.4700	uM
5-[(4-chlorophenyl)sulfanylmethyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	1.9300	uM
5-[(4-ethylphenoxy)methyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	1.9600	uM
5-[(3-phenylphenoxy)methyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	2.8400	uM
5-[(4-chloro-2,5-dimethylphenyl)sulfinylmethyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	2.8800	uM
5-[(3,5-diphenylphenoxy)methyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	3.7000	uM
5-[(4-chlorophenyl)sulfonylmethyl]-1,2-dihydropyrazol-3-one	700403: Inhibition of SOD1 G93A mutant aggregation-induced cytotoxicity in rat PC12 cells incubated for 24 hrs and measured 72 hrs post compound dose by cytotoxicity protection assay	ec50	4.7000	uM

CTD chemical–gene interactions

408 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Copper	decreases reaction, affects cotreatment, increases activity, decreases response to substance, decreases expression (+9 more)	23
sodium arsenite	decreases expression, decreases reaction, increases reaction, affects response to substance, affects cotreatment (+4 more)	22
Hydrogen Peroxide	increases metabolic processing, increases chemical synthesis, decreases response to substance, decreases expression, decreases reaction (+11 more)	19
Paraquat	decreases degradation, increases response to substance, increases reaction, decreases expression, increases activity (+5 more)	14
Cadmium	increases abundance, decreases expression, affects cotreatment, affects binding, decreases activity (+6 more)	13
Cadmium Chloride	decreases expression, increases expression, affects folding, increases abundance, decreases localization (+4 more)	13
Acetylcysteine	increases degradation, increases abundance, increases reaction, decreases reaction, increases expression (+3 more)	12
Particulate Matter	affects cotreatment, decreases activity, decreases reaction, increases abundance, increases expression (+3 more)	11
Zinc	affects binding, decreases reaction, affects cotreatment, decreases activity, increases reaction (+2 more)	9
bisphenol A	decreases expression, decreases reaction, increases expression, affects expression	8
Glucose	decreases reaction, increases degradation, increases reaction, affects cotreatment, increases expression (+4 more)	8
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	8
Arsenic	decreases expression, decreases activity, increases expression, affects expression, increases abundance (+1 more)	7
Quercetin	affects cotreatment, decreases expression, increases expression, affects expression, decreases reaction	7
Resveratrol	affects secretion, decreases expression, decreases reaction, increases ubiquitination, increases expression (+4 more)	6
Acetaminophen	increases secretion, decreases activity, decreases expression, increases expression, increases reaction (+1 more)	6
Ascorbic Acid	affects cotreatment, increases expression, decreases activity, decreases reaction, decreases expression (+1 more)	6
Benzo(a)pyrene	affects cotreatment, increases expression, decreases expression, increases methylation, decreases reaction	6
Oxygen	increases reaction, increases expression, affects cotreatment, increases metabolic processing, decreases response to substance (+2 more)	6
Superoxides	affects activity, affects binding, increases abundance, decreases reaction, decreases abundance (+2 more)	6
Cisplatin	decreases response to substance, increases expression, affects cotreatment, decreases expression	5
Doxorubicin	affects expression, affects cotreatment, increases expression, increases reaction	5
Plant Extracts	increases expression, affects expression, affects reaction, decreases expression, decreases activity (+2 more)	5
Sodium Selenite	increases expression, affects binding, decreases expression, affects localization, increases activity (+1 more)	5
lead acetate	decreases expression, decreases reaction, increases abundance, increases expression, increases activity (+1 more)	4
arsenite	affects binding, increases reaction, decreases reaction, increases expression, increases abundance	4
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases reaction, increases degradation, decreases expression, increases response to substance, increases expression (+2 more)	4
chromium hexavalent ion	decreases expression, increases expression, decreases response to substance	4
monomethylarsonous acid	increases expression	4
Rosiglitazone	affects cotreatment, increases expression, decreases reaction, decreases expression	4

ChEMBL screening assays

38 unique, capped per target: 32 binding, 5 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1105283	Binding	Binding affinity to human GST-SOD1 expressed in Escherichia coli Rosetta at 100 uM in presence of human plasma by reverse phase HPLC analysis	Improving binding specificity of pharmacological chaperones that target mutant superoxide dismutase-1 linked to familial amyotrophic lateral sclerosis using computational methods. — J Med Chem
CHEMBL4412934	ADMET	Inhibition of human erythrocyte CuZn-SOD by UV-Visible spectrophotometric method	New polyamine drugs as more effective antichagas agents than benznidazole in both the acute and chronic phases. — Eur J Med Chem
CHEMBL5253366	Functional	Effect on human SOD1 protein homeostasis in ALS mouse model assessed as survival relative to control	Therapeutic progress in amyotrophic lateral sclerosis-beginning to learning. — Eur J Med Chem

Cellosaurus cell lines

95 cell lines: 69 induced pluripotent stem cell, 15 finite cell line, 9 transformed cell line, 1 cancer cell line, 1 hybrid cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_8997	27b	Induced pluripotent stem cell	Female
CVCL_8998	27e	Induced pluripotent stem cell	Female
CVCL_8999	29a	Induced pluripotent stem cell	Female
CVCL_9000	29b	Induced pluripotent stem cell	Female
CVCL_9001	29d	Induced pluripotent stem cell	Female
CVCL_9002	29e	Induced pluripotent stem cell	Female
CVCL_A8PZ	HeLa SOD1 KO	Cancer cell line	Female
CVCL_A9P9	ND39028	Finite cell line	Male
CVCL_A9SS	CS24iALS-SOD1E50Kn9	Induced pluripotent stem cell	Female
CVCL_B522	29c	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

299 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00542412	PHASE4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	PHASE4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	PHASE4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	PHASE4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	PHASE4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	PHASE4	RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT00021697	PHASE3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	PHASE3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	PHASE3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	PHASE3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	PHASE3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	PHASE3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	PHASE3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	PHASE3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	PHASE3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	PHASE3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	PHASE3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	PHASE3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	PHASE3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	PHASE3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	PHASE3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	PHASE3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	PHASE3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	PHASE3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	PHASE3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	PHASE3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	PHASE3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	PHASE3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	PHASE3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	PHASE3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	PHASE3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT03800524	PHASE3	UNKNOWN	Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
NCT03836716	PHASE3	TERMINATED	Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
NCT03948178	PHASE3	TERMINATED	Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
NCT04165824	PHASE3	COMPLETED	Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04248465	PHASE3	TERMINATED	An Efficacy and Safety Study of Ravulizumab in ALS Participants
NCT04569084	PHASE3	TERMINATED	Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS