SOD2

Chr 6

superoxide dismutase 2

Also known as: GC1, GClnc1, IPO-B, IPOB, MNSOD, MVCD6, Mn-SOD, lncRNA-GC1

NCBI Gene: 6648ENSG00000291237UniProt: P04179

This gene is a member of the iron/manganese superoxide dismutase family. It encodes a mitochondrial protein that forms a homotetramer and binds one manganese ion per subunit. This protein binds to the superoxide byproducts of oxidative phosphorylation and converts them to hydrogen peroxide and diatomic oxygen. Mutations in this gene have been associated with idiopathic cardiomyopathy (IDC), premature aging, sporadic motor neuron disease, and cancer. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 1. [provided by RefSeq, Apr 2016]

Primary Disease Associations & Inheritance

{Microvascular complications of diabetes 6}MIM #612634
86
ClinVar variants
25
Pathogenic / LP
0.15
pLI score
12
Active trials
Clinical Summary— SOD2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 54 VUS of 86 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.
0.75LOEUF
pLI 0.155
Z-score 2.11
OE 0.29 (0.13–0.75)
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.
0.89Z-score
OE missense 0.77 (0.65–0.92)
93 obs / 120.4 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.0.29 (0.13–0.75)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.65–0.92)
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.1.01
0≤1.21.6
LoF obs/exp: 3 / 10.3Missense obs/exp: 93 / 120.4Syn Z: -0.06

ClinVar Variant Classifications

86 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic1
VUS54
Likely Benign5
Benign1
Conflicting1
24
Pathogenic
1
Likely Pathogenic
54
VUS
5
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
1
0
1
VUS
0
46
8
0
54
Likely Benign
0
3
1
1
5
Benign
0
0
0
1
1
Conflicting
—1
Total04934286

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

View in ClinVar →

Protein Context — Lollipop Plot

SOD2 · 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

{Microvascular complications of diabetes 6}

MIM #612634

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
AMPK activation coupling SENP1-Sirt3 axis protects against acute kidney injury.
Zhu M et al.·Mol Ther
2023
Superoxide dismutases: role in redox signaling, vascular function, and diseases.
Fukai T et al.·Antioxid Redox Signal
2011Review
Endoplasmic Reticulum Stress Promotes the Expression of TNF-α in THP-1 Cells by Mechanisms Involving ROS/CHOP/HIF-1α and MAPK/NF-κB Pathways.
Akhter N et al.·Int J Mol Sci
2023Functional
Endothelial MICU1 protects against vascular inflammation and atherosclerosis by inhibiting mitochondrial calcium uptake.
Sun L et al.·J Clin Invest
2025
Urinary proteomics identifies distinct immunological profiles of sepsis associated AKI sub-phenotypes.
Stanaway IB et al.·Crit Care
2024
Reprogramming Lung Redox Homeostasis by NIR Driven Ultra-Small Pd Loaded Covalent Organic Framework Inhibits NF-κB Pathway for Acute Lung Injury Immunotherapy.
Lei D et al.·Adv Sci (Weinh)
2025
A novel HIF-2α targeted inhibitor suppresses hypoxia-induced breast cancer stemness via SOD2-mtROS-PDI/GPR78-UPR(ER) axis.
Yan Y et al.·Cell Death Differ
2022
Sex-Specific Effects of Cholesteryl Ester Transfer Protein (CETP) on the Perivascular Adipose Tissue.
Lazaro CM et al.·Function (Oxf)
2024
A Comprehensive Multiomics Signature of Doxorubicin-Induced Cellular Senescence in the Postmenopausal Human Ovary.
Devrukhkar PR et al.·Aging Cell
2025
Association between SOD2 V16A variant and urological cancer risk.
Zhang LF et al.·Aging (Albany NY)
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Carnosine Alleviates High Glucose-Induced Renal Tubular Cell Pyroptosis by Activating the AMPK/SIRT3/SOD2 Pathway.
Zhao K et al.·Free Radic Res
2026
Irisin Mitigates Myocardial Hypoxia/Reoxygenation Injury by Preserving Mitochondrial Redox Homeostasis via the UCP2-SOD2 Axis.
Xu Y et al.·Protein Pept Lett
2026
Resveratrol‒loaded self‒assembled tetrahedral framework nucleic acids reshape the epileptic microenvironment by regulating oxidative stress and neuroinflammation via the SIRT3/SOD2 pathway.
Cui J et al.·J Nanobiotechnology
2026
SIRT1 agonist SRT1720 alleviates cerebral ischemia-reperfusion injury by inhibiting lactate-mediated SOD2 Lactylation and suppressing NCOA4-mediated ferritinophagy-ferroptosis.
Qi X et al.·Cell Signal
2026
Urolithin A alleviates vascular remodeling through mitochondrial SIRT3-mediated SOD2 deacetylation and antioxidation in hypertensive rats.
Dai M et al.·Redox Rep
2026🔓 Open AccessFunctional
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
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)
Amyotrophic Lateral Sclerosis

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RAG-17 in Subjects With Amyotrophic Lateral Sclerosis (ALS) With Superoxide Dismutase Type 1 (SOD1) Gene Mutation

RECRUITING
NCT06556394Phase PHASE1Ractigen Therapeutics.Started 2024-12-24
RAG-17Placebo

External Resources

Links to major genomics databases and tools