SELENOT

Chr 3

selenoprotein T

Also known as: SELT

NCBI Gene: 51714 ENSG00000198843 UniProt: P62341 OMIM: 607912

This gene encodes a selenoprotein, containing a selenocysteine (Sec) residue at the active site. Sec is encoded by the UGA codon that normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. This protein is localized in the endoplasmic reticulum. It belongs to the SelWTH family that possesses a thioredoxin-like fold and a conserved CxxU (C is cysteine, U is Sec) motif found in several redox active proteins. Studies in mice indicate a crucial role for this gene in the protection of dopaminergic neurons against oxidative stress in Parkinson's disease, and in the control of glucose homeostasis in pancreatic beta-cells. Pseudogenes of this locus have been identified on chromosomes 9 and 5. [provided by RefSeq, Sep 2017]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.82

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.115

Z-score 1.94

OE 0.32 (0.14–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.01Z-score

OE missense 0.70 (0.57–0.86)

65 obs / 92.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.32 (0.14–0.82)

0≤0.351.4

Missense OE?0.70 (0.57–0.86)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 3 / 9.4Missense obs/exp: 65 / 92.4Syn Z: -0.64

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 440

190 rare PASS variants

Rare truncating (LoF)

1 in 4,700

17 rare PASS variants

Rare synonymous (reference)

1 in 1,400

87 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SELENOT. 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 460	1 in 4,000
South Asian	~43k	1 in 210	≈ 1 in 13,000
Remaining (unassigned)	~30k	1 in 220	≈ 1 in 15,000
European (Finnish)	~27k	1 in 1,600	≈ 1 in 27,000
Admixed American	~22k	1 in 500	≈ 1 in 5,700
African / African American	~21k	1 in 250	none seen
East Asian	~20k	1 in 1,100	none seen
Ashkenazi Jewish	~13k	1 in 770	none seen
Middle Eastern	~2,882	1 in 420	none seen

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): 3 of 5 coding exons well covered in gnomAD exomes; exons 2, 4 marginal. Genomes: all 5.? see exons ↓