SELENON

Chr 1AR

selenoprotein N

NCBI Gene: 57190ENSG00000162430UniProt: Q9NZV5

Plays an important role in cell protection against oxidative stress and in the regulation of redox-related calcium homeostasis. Regulates the calcium level of the ER by protecting the calcium pump ATP2A2 against the oxidoreductase ERO1A-mediated oxidative damage. Within the ER, ERO1A activity increases the concentration of H(2)O(2), which attacks the luminal thiols in ATP2A2 and thus leads to cysteinyl sulfenic acid formation (-SOH) and SEPN1 reduces the SOH back to free thiol (-SH), thus restoring ATP2A2 activity (PubMed:25452428). Acts as a modulator of ryanodine receptor (RyR) activity: protects RyR from oxidation due to increased oxidative stress, or directly controls the RyR redox state, regulating the RyR-mediated calcium mobilization required for normal muscle development and differentiation (PubMed:18713863, PubMed:19557870)

Primary Disease Associations & Inheritance

Congenital myopathy 3 with rigid spineMIM #602771
AR
827
ClinVar variants
65
Pathogenic / LP
0.00
pLI score
3
Active trials
Clinical Summary— SELENON
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
65 Pathogenic / Likely Pathogenic· 196 VUS of 827 total submissions
💊
Clinical Trials
3 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.
1.02LOEUF
pLI 0.000
Z-score 1.49
OE 0.69 (0.47–1.02)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.42Z-score
OE missense 0.93 (0.84–1.03)
275 obs / 295.5 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.0.69 (0.47–1.02)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.84–1.03)
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.1.15
0≤1.21.6
LoF obs/exp: 18 / 26.2Missense obs/exp: 275 / 295.5Syn Z: -1.37

ClinVar Variant Classifications

827 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic26
VUS196
Likely Benign199
Benign23
Conflicting4
39
Pathogenic
26
Likely Pathogenic
196
VUS
199
Likely Benign
23
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
27
1
11
0
39
Likely Pathogenic
17
5
4
0
26
VUS
4
169
21
2
196
Likely Benign
0
2
95
102
199
Benign
0
0
23
0
23
Conflicting
—4
Total48177154104487

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

View in ClinVar →

Protein Context — Lollipop Plot

SELENON · protein map & ClinVar variants

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

Gene2Phenotype Curations

SELENON-related myopathy

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
SELENOPROTEIN N; SELENON
MIM #606210 · *

Congenital myopathy 3 with rigid spine

MIM #602771

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A 5-year natural history study in LAMA2-related muscular dystrophy and SELENON-related myopathy: the Extended LAST STRONG study.
de Laat ECM et al.·BMC Neurol
2024Natural history
A review of core myopathy: central core disease, multiminicore disease, dusty core disease, and core-rod myopathy.
Ogasawara M et al.·Neuromuscul Disord
2021Review
Cardiac Involvement in LAMA2-Related Muscular Dystrophy and SELENON-Related Congenital Myopathy: A Case Series.
Bouman K et al.·J Neuromuscul Dis
2024Cohort
SELENON-Related Myopathy Across the Life Span, a Cross-Sectional Study for Preparing Trial Readiness.
Bouman K et al.·J Neuromuscul Dis
2023
Respiratory function in LAMA2-related muscular dystrophy and SELENON-related congenital myopathy, a 1.5-year natural history study.
Bouman K et al.·Eur J Paediatr Neurol
2024Natural history
Bone quality in LAMA2-related muscular dystrophy and SELENON-related congenital myopathy, a one-year prospective natural history study.
Bouman K et al.·Neuromuscul Disord
2024Natural history
Natural history, outcome measures and trial readiness in LAMA2-related muscular dystrophy and SELENON-related myopathy in children and adults: protocol of the LAST STRONG study.
Bouman K et al.·BMC Neurol
2021Natural history
Human Genetic Disorders Resulting in Systemic Selenoprotein Deficiency.
Schoenmakers E et al.·Int J Mol Sci
2021Review
Genetics and muscle pathology in the diagnosis of muscular dystrophies: An update.
Narasimhaiah D et al.·Indian J Pathol Microbiol
2022Review
HMGCS1 variants cause rigid spine syndrome amenable to mevalonic acid treatment in an animal model.
Dofash LNH et al.·Brain
2025Functional
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
LAMA2-related Muscular DystrophySELENON-related Myopathy

A 5-year Natural History Study in LAMA2-related Muscular Dystrophy and SELENON-related Myopathy.

RECRUITING
NCT06132750Radboud University Medical CenterStarted 2023-10-06
No intervention
Central Core DiseaseCentronuclear MyopathyCongenital Fiber Type Disproportion

Molecular and Genetic Studies of Congenital Myopathies

RECRUITING
NCT00272883Boston Children's HospitalStarted 2003-08
Congenital Muscular Dystrophy With ITGA7 (Integrin Alpha-7) DeficiencyAlpha-Dystroglycanopathy (Congenital Muscular Dystrophy and Abnormal Glycosylation of Dystroglycan With Severe Epilepsy)Alpha-Dystroglycanopathy (Congenital Muscular Dystrophy With Fatty Liver and Infantile-onset Cataract Caused by TRAPPC11 Mutations)

Congenital Muscle Disease Study of Patient and Family Reported Medical Information

RECRUITING
NCT01403402Cure CMDStarted 2009-09

External Resources

Links to major genomics databases and tools