SELENOS
protein-codingselenoprotein S, the group of Selenoproteins
Gene summary
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]
- VIMP
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.0 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 SELENOS variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018445.6. 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 | 1 | 2 | 3 | |||
| missense | 36 | 1 | 37 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 37 | 1 | 3 | 41 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060915.2 | 6 | MANE Select | |
| Ensembl | ENSP00000433541.1 | 6 | MANE Select | |
| RefSeq | NP_982298.2 | 6 | Standard | |
| Ensembl | ENSP00000381282.3 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- Selenium Micronutrient Network
- Selenium Metabolism and Selenoproteins
- Post-translational protein modification
- Metabolism of proteins
Biological Process
- negative regulation of acute inflammatory response to antigenic stimulus
- regulation of gluconeogenesis
- ER overload response
- response to glucose
- protein ubiquitination
Molecular Function
- protein binding
- antioxidant activity
- enzyme binding
- signaling receptor activity
- ATPase binding
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- cytoplasmic microtubule
- plasma membrane
- integral component of endoplasmic reticulum membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000398226
- Coding exons
- 6
- Length
- 6684
- Individuals with no LoFs
- 124583
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 40
- Defined
- 124623
- p
- 0.000160
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.610 | 112 | 95.2 | 1.18 | 0.00000525 | 1163 |
| Missense (PolyPhen) | 37 | 35.352 | 1.0466 | 478 | ||
| Synonymous | -0.296 | 41 | 38.7 | 1.06 | 0.00000221 | 369 |
| Loss of Function | -0.277 | 13 | 12.0 | 1.09 | 6.10e-7 | 147 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00034 | 0.00032 | rare |
| Latino/Admixed American | 0.00035 | 0.00032 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00012 | 0.00011 | rare |
| Finnish | 0.000051 | 0.000046 | rare |
| European (Non-Finnish) | 0.00016 | 0.00014 | rare |
| South Asian | 0.000067 | 0.000065 | rare |
| Other | 0.00054 | 0.00050 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the degradation process of misfolded endoplasmic reticulum (ER) luminal proteins. Participates in the transfer of misfolded proteins from the ER to the cytosol, where they are destroyed by the proteasome in a ubiquitin-dependent manner. Probably acts by serving as a linker between DERL1, which mediates the retrotranslocation of misfolded proteins into the cytosol, and the ATPase complex VCP, which mediates the translocation and ubiquitination. {ECO:0000269|PubMed:15215856}.;
Intolerance Scores
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 46.49