SELENOK
protein-codingselenoprotein K, the group of Selenoproteins
Gene summary
The protein encoded by this gene belongs to the selenoprotein K family. It is a transmembrane protein that is localized in the endoplasmic reticulum (ER), and is involved in ER-associated degradation (ERAD) of misfolded, glycosylated proteins. It also has a role in the protection of cells from ER stress-induced apoptosis. Knockout studies in mice show the importance of this gene in promoting Ca(2+) flux in immune cells and mounting effective immune response. 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. Pseudogenes of this locus have been identified on chromosomes 6 and 19.[provided by RefSeq, Aug 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.5 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 SELENOK variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021237.5. 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 | 13 | 1 | 14 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 15 | 1 | 0 | 16 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_067060.2 | 5 | MANE Select | |
| Ensembl | ENSP00000418813.1 | 5 | MANE Select | |
| Ensembl | ENSP00000417272.1 | 4 | Standard | |
| Ensembl | ENSP00000813377.1 | 5 | 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
- positive regulation of defense response to virus by host
- calcium ion transport
- response to oxidative stress
- macrophage derived foam cell differentiation
- protein palmitoylation
Molecular Function
- protein binding
- identical protein binding
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- Golgi apparatus
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000495461
- Coding exons
- 5
- Length
- 7579
- Individuals with no LoFs
- 125047
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 14
- Defined
- 125061
- p
- 0.0000560
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.339 | 37 | 43.3 | 0.855 | 0.00000214 | 587 |
| Missense (PolyPhen) | 8 | 14.664 | 0.54556 | 214 | ||
| Synonymous | -0.244 | 14 | 12.9 | 1.09 | 5.54e-7 | 167 |
| Loss of Function | 0.0775 | 6 | 6.21 | 0.966 | 2.62e-7 | 85 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for Ca(2+) flux in immune cells and plays a role in T-cell proliferation and in T-cell and neutrophil migration (By similarity). Involved in endoplasmic reticulum- associated degradation (ERAD) of soluble glycosylated proteins (PubMed:22016385). Required for palmitoylation and cell surface expression of CD36 and involved in macrophage uptake of low- density lipoprotein and in foam cell formation (By similarity). Together with ZDHHC6, required for palmitoylation of ITPR1 in immune cells, leading to regulate ITPR1 stability and function (PubMed:25368151). Plays a role in protection of cells from ER stress-induced apoptosis (PubMed:20692228). Protects cells from oxidative stress when overexpressed in cardiomyocytes (PubMed:16962588). {ECO:0000250|UniProtKB:Q9JLJ1, ECO:0000269|PubMed:16962588, ECO:0000269|PubMed:20692228, ECO:0000269|PubMed:22016385, ECO:0000269|PubMed:25368151}.;
Intolerance Scores
- RVIS EVS
- 0.19
- RVIS percentile EVS
- 66.57