SELENOT
protein-codingselenoprotein T, the group of Selenoproteins
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~27.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SELENOT variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016275.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 21 | 21 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 22 | 0 | 0 | 22 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057359.2 | 5 | MANE Select | |
| Ensembl | ENSP00000418910.1 | 5 | MANE Select | |
| Ensembl | ENSP00000417932.1 | 4 | Standard | |
| Ensembl | ENSP00000417932.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Selenium Micronutrient Network
- Selenium Metabolism and Selenoproteins
Biological Process
- selenocysteine incorporation
- positive regulation of cytosolic calcium ion concentration
- response to glucose
- pancreas development
- insulin secretion involved in cellular response to glucose stimulus
Molecular Function
- thioredoxin-disulfide reductase activity
- selenium binding
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000471696
- Coding exons
- 5
- Length
- 27561
- Individuals with no LoFs
- 124601
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 124608
- p
- 0.0000281
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.01 | 65 | 92.4 | 0.703 | 0.00000429 | 1259 |
| Missense (PolyPhen) | 6 | 21.794 | 0.27531 | 327 | ||
| Synonymous | -0.643 | 39 | 34.2 | 1.14 | 0.00000152 | 364 |
| Loss of Function | 1.94 | 3 | 9.41 | 0.319 | 4.66e-7 | 123 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000031 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Selenoprotein with thioredoxin reductase-like oxidoreductase activity (By similarity). Protects dopaminergic neurons against oxidative stress ans cell death (PubMed:26866473). Involved in ADCYAP1/PACAP-induced calcium mobilization and neuroendocrine secretion (By similarity). Plays a role in fibroblast anchorage and redox regulation (By similarity). In gastric smooth muscle, modulates the contraction processes through the regulation of calcium release and MYLK activation (By similarity). In pancreatic islets, involved in the control of glucose homeostasis, contributes to prolonged ADCYAP1/PACAP- induced insulin secretion (By similarity). {ECO:0000250|UniProtKB:P62342, ECO:0000250|UniProtKB:Q1H5H1, ECO:0000269|PubMed:26866473}.;
- Disease
- DISEASE: Note=mRNA levels are increased more than 200-folds in the caudate putamen from Parkinson disease (PD) patients compared to control subjects. In conditional brain knockout mice, treatment with PD-inducing neurotoxins provoke rapid and severe parkinsonian-like motor defects. {ECO:0000269|PubMed:26866473}.;
Intolerance Scores
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 49.39
Essentials
- Essential (gene trap)
- N