SOD1

Chr 21ADAR

superoxide dismutase 1

Also known as: ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP, hSod1, homodimer

NCBI Gene: 6647ENSG00000142168UniProt: P00441

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. [provided by RefSeq, Jul 2020]

Primary Disease Associations & Inheritance

Amyotrophic lateral sclerosis 1MIM #105400
ADAR
Spastic tetraplegia and axial hypotonia, progressiveMIM #618598
AR
379
ClinVar variants
188
Pathogenic / LP
0.18
pLI score
12
Active trials
Clinical Summary— SOD1
🧬
Gene-Disease Validity (ClinGen)
amyotrophic lateral sclerosis type 1 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
188 Pathogenic / Likely Pathogenic· 90 VUS of 379 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.98LOEUF
pLI 0.177
Z-score 1.62
OE 0.31 (0.13–0.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.84Z-score
OE missense 0.75 (0.61–0.92)
65 obs / 87.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.31 (0.13–0.98)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.61–0.92)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.28
0≤1.21.6
LoF obs/exp: 2 / 6.4Missense obs/exp: 65 / 87.0Syn Z: -1.27

ClinVar Variant Classifications

379 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic106
Likely Pathogenic82
VUS90
Likely Benign63
Benign19
Conflicting19
106
Pathogenic
82
Likely Pathogenic
90
VUS
63
Likely Benign
19
Benign
19
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
46
59
0
106
Likely Pathogenic
5
72
5
0
82
VUS
5
53
30
2
90
Likely Benign
0
0
35
28
63
Benign
0
0
19
0
19
Conflicting
—19
Total1117114830379

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SOD1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Amyotrophic lateral sclerosis 1

MIM #105400

Molecular basis of disorder known

Autosomal dominantAutosomal recessive

Spastic tetraplegia and axial hypotonia, progressive

MIM #618598

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — SOD1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Antisense oligonucleotides extend survival and reverse decrement in muscle response in ALS models.
McCampbell A et al.·J Clin Invest
2018Functional
SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity.
Berdyński M et al.·Sci Rep
2022
Silence superoxide dismutase 1 (SOD1): a promising therapeutic target for amyotrophic lateral sclerosis (ALS).
Abati E et al.·Expert Opin Ther Targets
2020Review
Design of a Randomized, Placebo-Controlled, Phase 3 Trial of Tofersen Initiated in Clinically Presymptomatic SOD1 Variant Carriers: the ATLAS Study.
Benatar M et al.·Neurotherapeutics
2022Clinical trial
Genetic variability in sporadic amyotrophic lateral sclerosis.
Van Daele SH et al.·Brain
2023
Amyotrophic lateral sclerosis caused by SOD1 variants: from genetic discovery to disease prevention.
Benatar M et al.·Lancet Neurol
2025
Variability in SOD1-associated amyotrophic lateral sclerosis: geographic patterns, clinical heterogeneity, molecular alterations, and therapeutic implications.
Huang M et al.·Transl Neurodegener
2024Review
Long-Term Tofersen in SOD1 Amyotrophic Lateral Sclerosis.
Miller TM et al.·JAMA Neurol
2026Clinical trial
Allogeneic B cell immunomodulatory therapy in amyotrophic lateral sclerosis.
Sîrbulescu RF et al.·FASEB J
2024
[Motor neuron diseases].
Petri S et al.·Nervenarzt
2011
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Amyotrophic Lateral Sclerosis Associated With a SOD1 Gene Mutation

A Study of BIIB067 (Tofersen) Initiated in Clinically Presymptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation

ACTIVE NOT RECRUITING
NCT04856982Phase PHASE3BiogenStarted 2021-05-17
TofersenPlacebo
B Acute Lymphoblastic LeukemiaB Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1B Acute Lymphoblastic Leukemia, BCR-ABL1-Like

Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma

RECRUITING
NCT05602194Phase PHASE3Children's Oncology GroupStarted 2023-08-24
Biospecimen CollectionCalaspargase PegolLevocarnitine
Amyotrophic Lateral Sclerosis

A Study to Investigate the Safety and Pharmacodynamics of a Single Intrathecal Injection (IT) of INS1202 in Participants With Amyotrophic Lateral Sclerosis (ALS)

RECRUITING
NCT07290062Phase PHASE1Insmed Gene Therapy LLCStarted 2026-01-09
INS1202
Physiological AdaptationsSport PerformanceAerobic Capacity

Molecular Hydrogen Inhalation: Effects on Health, Exercise Capacity and Inflammatory Response - in Vivo/in Vitro Studies

NOT YET RECRUITING
NCT07130942Phase NAGdansk University of Physical Education and SportStarted 2025-10-01
Inhalation using a molecular hydrogen generator
Amyotrophic Lateral Sclerosis

A Study to Assess the Safety, Tolerability, and Pharmacology of Darifenacin in Patients With ALS

RECRUITING
NCT06249867Phase PHASE2Oliver BlanchardStarted 2024-11-08
Darifenacin 7.5 MG Extended Release Oral TabletPlacebo
Neurodegenerative DisordersParkinson DiseaseAlzheimer Disease

An Innovative Method in SAliva Samples for the Early Differential Diagnosis of High-impact NeuroDegenerative Diseases Through Raman Spectroscopy

ENROLLING BY INVITATION
NCT06875739Fondazione Don Carlo Gnocchi OnlusStarted 2025-02-14
Rheumatoid ArthritisOsteoarthritisSarcopenia

Effect of Exercise Type on Muscle Quality in Patients With OA, SARC and RA: an Explorative Study

NOT YET RECRUITING
NCT06480643Phase NAAmsterdam UMC, location VUmcStarted 2024-12-01
High load exercise typeLow load exercise type
Transgender Individuals

Effects of Gender-Affirming Hormone Therapy on Cardiovascular, Metabolic, and Mental Health Outcomes in Transgender Adults.

NOT YET RECRUITING
NCT07394400Milagros Rocha BarajasStarted 2026-02-14
ALS

Amyotrophic Lateral Sclerosis (ALS) Families Project

RECRUITING
NCT03865420Columbia UniversityStarted 2018-09-11
Amyotrophic Lateral Sclerosis

A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)

RECRUITING
NCT07223723Phase PHASE4BiogenStarted 2025-12-11
Tofersen
Amyotrophic Lateral Sclerosis

Safety, Tolerability, and Exploratory Efficacy Study of Intrathecally Administered Gene Therapy AMT-162 in Adult Participants With SOD1 Amyotrophic Lateral Sclerosis (SOD1-ALS)

ACTIVE NOT RECRUITING
NCT06100276Phase PHASE1, PHASE2UniQure Biopharma B.V.Started 2024-08-01
AMT-162
Amyotrophic Lateral Sclerosis (ALS)Mutation in the Superoxide Dismutase-1 (SOD1) Gene

First in Human (FIH) Study of ALN-SOD in Adult Participants With Amyotrophic Lateral Sclerosis Associated With Mutation in the SOD1 Gene (SOD1-ALS)

RECRUITING
NCT06351592Phase PHASE1, PHASE2Regeneron PharmaceuticalsStarted 2024-08-28
ALN-SODDiluentPlacebo (PB)

External Resources

Links to major genomics databases and tools