SELENON

Chr 1AR

selenoprotein N

Also known as: CFTD, CMYO3, CMYP3, MDRS1, RSMD1, RSS, SELN, SEPN1

The encoded glycoprotein localizes to the endoplasmic reticulum where it protects cells against oxidative stress and regulates redox-related calcium homeostasis. Autosomal recessive mutations cause SEPN1-related myopathy, which encompasses four early-onset muscle disorders including rigid spine muscular dystrophy, multiminicore disease, desmin-related myopathy with Mallory-body inclusions, and congenital fiber-type disproportion. Loss of function appears to be the pathogenic mechanism in these congenital myopathies.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.021 OMIM phenotype
VCEP Guidelines: Congenital MyopathiesReleased
ClinGen Panel
Clinical SummarySELENON
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Gene-Disease Validity (ClinGen)
SELENON-related myopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
65 unique Pathogenic / Likely Pathogenic· 151 VUS of 399 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.02LOEUF
pLI 0.000
Z-score 1.49
OE 0.69 (0.471.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.42Z-score
OE missense 0.93 (0.841.03)
275 obs / 295.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.69 (0.471.02)
00.351.4
Missense OE0.93 (0.841.03)
00.61.4
Synonymous OE1.15
01.21.6
LoF obs/exp: 18 / 26.2Missense obs/exp: 275 / 295.5Syn Z: -1.37
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSELENON-related myopathyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.4884th %ile
GOF
0.6345th %ile
LOF
0.3939th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

399 submitted variants in ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic25
VUS151
Likely Benign135
Benign23
Conflicting13
40
Pathogenic
25
Likely Pathogenic
151
VUS
135
Likely Benign
23
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
29
2
9
0
40
Likely Pathogenic
15
9
1
0
25
VUS
3
132
14
2
151
Likely Benign
0
1
64
70
135
Benign
0
0
23
0
23
Conflicting
13
Total4714411172387

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →