SELENOP
protein-codingselenoprotein P, the group of Selenoproteins
Gene summary
This gene encodes a selenoprotein that is predominantly expressed in the liver and secreted into the plasma. This selenoprotein is unique in that it contains multiple selenocysteine (Sec) residues per polypeptide (10 in human), and accounts for most of the selenium in plasma. It has been implicated as an extracellular antioxidant, and in the transport of selenium to extra-hepatic tissues via apolipoprotein E receptor-2 (apoER2). Mice lacking this gene exhibit neurological dysfunction, suggesting its importance in normal brain function. 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. The mRNA for this selenoprotein contains two SECIS elements. The use of alternative polyadenylation sites, one located in between the two SECIS elements, results in two populations of mRNAs containing either both (predominant) or just the upstream SECIS element (PMID:27881738). Alternatively spliced transcript variants have also been found for this gene. [provided by RefSeq, Oct 2018]
- SEPP1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~87.5 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 SELENOP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005410.4. 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 | 2 | 1 | 3 | |||
| missense | 46 | 4 | 50 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 47 | 7 | 1 | 55 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005401.3 | 4 | MANE Select | |
| Ensembl | ENSP00000420939.1 | 4 | MANE Select | |
| RefSeq | NP_001078955.1 | 4 | Standard | |
| RefSeq | NP_001087195.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Selenium Micronutrient Network
- Integrin-mediated Cell Adhesion
- Selenium Metabolism and Selenoproteins
- ESC Pluripotency Pathways
- Platelet degranulation
Biological Process
- selenium compound metabolic process
- platelet degranulation
- response to oxidative stress
- brain development
- locomotory behavior
Molecular Function
- selenium binding
Cellular Component
- extracellular region
- extracellular space
- platelet dense granule lumen
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000514985
- Coding exons
- 4
- Length
- 87513
- Individuals with no LoFs
- 124701
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 98
- Defined
- 124799
- p
- 0.000393
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0124 | 197 | 197 | 0.998 | 0.00000962 | 2497 |
| Missense (PolyPhen) | 47 | 44.34 | 1.06 | 569 | ||
| Synonymous | 0.176 | 63 | 64.8 | 0.972 | 0.00000290 | 701 |
| Loss of Function | 1.27 | 12 | 17.8 | 0.675 | 0.00000112 | 199 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00019 | rare |
| Latino/Admixed American | 0.0014 | 0.0014 | notable |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00058 | 0.00056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00026 | 0.00026 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Might be responsible for some of the extracellular antioxidant defense properties of selenium or might be involved in the transport of selenium. May supply selenium to tissues such as brain and testis.;
Recessive Scores
- pRec
- 0.530
Intolerance Scores
- RVIS EVS
- 0.57
- RVIS percentile EVS
- 82.08