ALS Gene Library

SOD1

Superoxide Dismutase 1

SOD1 was the first major gene identified as a cause of familial ALS.

Pathogenic variants in SOD1 can cause ALS through toxic effects associated with abnormal SOD1 protein.

Different SOD1 variants can produce substantially different ages of onset and rates of progression.

Sources: Amyotrophic Lateral Sclerosis Overview · Evidence-Based Consensus Guidelines for ALS Genetic Testing and Counseling · FDA approves treatment of ALS associated with a mutation in the SOD1 gene · Ongoing accelerated-approval follow-up indications

Associated conditions

Primarily ALS. Cognitive and FTD involvement is much less characteristic than with C9orf72.

Sources: Amyotrophic Lateral Sclerosis Overview

ALS / FTD relationship

SOD1-associated disease is primarily an ALS phenotype. FTD overlap is less characteristic than in C9orf72-associated disease, but clinical assessment remains individualized.

Sources: Amyotrophic Lateral Sclerosis Overview

Typical inheritance pattern

Most SOD1-associated ALS is autosomal dominant.

Some variants can show recessive inheritance in particular populations.

Sources: Amyotrophic Lateral Sclerosis Overview

Penetrance

Penetrance varies by variant.

One universal SOD1 penetrance estimate should not be used without variant context.

Sources: Amyotrophic Lateral Sclerosis Overview

Clinical presentation

SOD1-associated ALS is clinically heterogeneous.

Different variants can differ in age of onset, upper versus lower motor-neuron involvement, speed of progression, and survival.

Sources: Amyotrophic Lateral Sclerosis Overview

Genetic testing considerations

SOD1 sequencing is included among the minimum recommended testing for people with ALS under consensus guidelines.

Variant interpretation should be handled with appropriate clinical and genetic expertise.

Sources: Evidence-Based Consensus Guidelines for ALS Genetic Testing and Counseling

Biomarkers

Neurofilament light has played an important role in SOD1 therapeutic development.

FDA accelerated approval of tofersen was based on reduction in plasma neurofilament light, considered reasonably likely to predict clinical benefit.

Sources: FDA approves treatment of ALS associated with a mutation in the SOD1 gene

Available treatments

QALSODY (tofersen) is FDA-approved for adults with ALS associated with a mutation in SOD1.

Sources: FDA approves treatment of ALS associated with a mutation in the SOD1 gene

Presymptomatic research

The ATLAS trial evaluates tofersen in clinically presymptomatic SOD1 mutation carriers.

Its goal is to evaluate whether initiating treatment before clinical ALS develops can delay disease emergence.

Sources: Ongoing accelerated-approval follow-up indications

Clinical trials

Search SOD1 ALS studies

Sources: ClinicalTrials.gov: Amyotrophic Lateral Sclerosis studies

Current research

Current research includes variant-specific SOD1 biology, antisense therapy, neurofilament biomarkers, and treatment before symptom onset.

Sources: FDA approves treatment of ALS associated with a mutation in the SOD1 gene · Ongoing accelerated-approval follow-up indications

Key research institutions / studies

  • ATLAS study of clinically presymptomatic SOD1 mutation carriers
  • ClinicalTrials.gov SOD1 studies
Search SOD1 studies on ClinicalTrials.gov

Sources: Ongoing accelerated-approval follow-up indications · ClinicalTrials.gov: Amyotrophic Lateral Sclerosis studies

Sources & Further Reading

These source cards link directly to the original material. External websites open in a new tab.

This information is for education and does not replace individualized medical advice, genetic counseling, diagnosis, or treatment. Genetic risk, penetrance, and testing implications can differ by gene, variant, family, and individual.

Last reviewed: 09-30-2026

Medical information should be reviewed periodically as genetic research and clinical trials change.

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