SECISBP2
protein-codingSECIS binding protein 2
Gene summary
The protein encoded by this gene is one of the essential components of the machinery involved in co-translational insertion of selenocysteine (Sec) into selenoproteins. Sec is encoded by the UGA codon, which normally signals translation termination. The recoding of UGA as Sec codon requires a Sec insertion sequence (SECIS) element; present in the 3' untranslated regions of eukaryotic selenoprotein mRNAs. This protein specifically binds to the SECIS element, which is stimulated by a Sec-specific translation elongation factor. Mutations in this gene have been associated with reduction in enzymatic activity of type II iodothyronine deiodinase (a selenoprotein) and abnormal thyroid hormone metabolism. Alternatively spliced transcript variants have been found for this gene. [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 ~41.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0800046
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0800046
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0012332
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0800046
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Endocrine; Musculoskeletal; Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
Comments: Findings, such as growth retardation, may be transient, and the overall phenotypic range has been described as wide
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SECISBP2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024077.5. 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 | 5 | 11 | 1 | 17 | ||
| missense | 1 | 123 | 8 | 3 | 135 | |
| nonsense | 3 | 4 | 1 | 8 | ||
| start loss | 0 | |||||
| frameshift | 2 | 4 | 6 | |||
| splice donor/acceptor (+/-2bp) | 1 | 2 | 2 | 5 | ||
| Total | 6 | 11 | 131 | 19 | 4 | 171 |
Highest pathogenic variant AF is 0.00003035913
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_076982.3 | 17 | MANE Select | |
| Ensembl | ENSP00000364965.3 | 17 | MANE Select | |
| RefSeq | NP_001269617.1 | 17 | Standard | |
| RefSeq | NP_001269618.1 | 16 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Selenocysteine synthesis
- Metabolism of amino acids and derivatives
- Metabolism
- Selenoamino acid metabolism
Biological Process
- selenocysteine incorporation
- striatum development
- neuron development
- negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
Molecular Function
- RNA binding
- mRNA 3'-UTR binding
- protein binding
- selenocysteine insertion sequence binding
- ribonucleoprotein complex binding
Cellular Component
- nucleus
- mitochondrion
- ribonucleoprotein complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000375807
- Coding exons
- 17
- Length
- 41137
- Individuals with no LoFs
- 125564
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 184
- Defined
- 125748
- p
- 0.000732
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.00520 | 439 | 439 | 0.999 | 0.0000230 | 5580 |
| Missense (PolyPhen) | 131 | 134.64 | 0.97295 | 1780 | ||
| Synonymous | -2.23 | 201 | 165 | 1.22 | 0.00000872 | 1645 |
| Loss of Function | 1.41 | 33 | 42.9 | 0.768 | 0.00000234 | 546 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00050 | 0.00049 | rare |
| Latino/Admixed American | 0.0013 | 0.0013 | notable |
| Ashkenazi Jewish | 0.00069 | 0.00069 | rare |
| East Asian | 0.0011 | 0.0011 | notable |
| Finnish | 0.00042 | 0.00042 | rare |
| European (Non-Finnish) | 0.00060 | 0.00060 | rare |
| South Asian | 0.00072 | 0.00072 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds to the SECIS element in the 3'-UTR of some mRNAs encoding selenoproteins. Binding is stimulated by SELB.;
Recessive Scores
- pRec
- 0.0900
Intolerance Scores
- LoFtool
- 0.878
- RVIS EVS
- -0.53
- RVIS percentile EVS
- 20.82
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.479
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |