SELENOS

Chr 15

selenoprotein S

Also known as: AD-015, ADO15, SBBI8, SELS, SEPS1, VIMP

NCBI Gene: 55829 ENSG00000131871 UniProt: Q9BQE4 OMIM: 607918

The protein is a transmembrane selenoprotein in the endoplasmic reticulum that facilitates degradation of misfolded proteins by linking retrotranslocation machinery to the proteasome system. Mutations cause SELENOS-related myopathy, an autosomal recessive disorder characterized by early-onset progressive muscle weakness and rigidity affecting axial muscles, with some patients developing cataracts and hearing loss. The gene shows very low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a transmembrane protein that is localized in the endoplasmic reticulum (ER). It is involved in the degradation process of misfolded proteins in the ER, and may also have a role in inflammation control. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec). Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Two additional phylogenetically conserved stem-loop structures (Stem-loop 1 and Stem-loop 2) in the 3' UTR of this mRNA have been shown to function as modulators of Sec insertion. An alternatively spliced transcript variant, lacking the SECIS element and encoding a non-Sec containing shorter isoform, has been described for this gene (PMID:23614019). [provided by RefSeq, Jul 2017]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.69

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.69LOEUF

pLI 0.000

Z-score -0.28

OE 1.09 (0.70–1.69)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.61Z-score

OE missense 1.18 (1.01–1.38)

112 obs / 95.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.09 (0.70–1.69)

0≤0.351.4

Missense OE?1.18 (1.01–1.38)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 13 / 12.0Missense obs/exp: 112 / 95.2Syn Z: -0.30

Background carrier burden — how many people carry a rare variant somewhere in SELENOS?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

427 rare PASS variants

Rare truncating (LoF)

1 in 480

108 rare PASS variants

Rare synonymous (reference)

1 in 260

176 rare PASS variants

Rare missense and truncating variants are carried at similar rates in SELENOS; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 750
South Asian	~43k	1 in 110	1 in 590
Remaining (unassigned)	~30k	1 in 86	1 in 520
European (Finnish)	~27k	1 in 1,100	≈ 1 in 6,300
Admixed American	~22k	1 in 100	1 in 940
African / African American	~21k	1 in 100	1 in 910
East Asian	~20k	1 in 120	1 in 1,300
Ashkenazi Jewish	~13k	1 in 190	none seen
Middle Eastern	~2,884	1 in 120	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 6 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 6.? see exons ↓