SELENBP1
protein-codingselenium binding protein 1
Gene summary
This gene encodes a member of the selenium-binding protein family. Selenium is an essential nutrient that exhibits potent anticarcinogenic properties, and deficiency of selenium may cause certain neurologic diseases. The effects of selenium in preventing cancer and neurologic diseases may be mediated by selenium-binding proteins, and decreased expression of this gene may be associated with several types of cancer. The encoded protein may play a selenium-dependent role in ubiquitination/deubiquitination-mediated protein degradation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Apr 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0005090
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0029144
Submitter: ClinGen
*SELENBP1* was first reported in relation to autosomal recessive extraoral halitosis due to methanethiol oxidase deficiency in 2018 (Pol, et al., 2018, PMID:29255262). Indviduals reported with the disorder all share extra-oral halitosis with a specific "cabbage-like"odor caused by elevated levels of methanethiol and dimethylsulfide in the breath. Additionally, indviduals with the disorder demonstrate reduced SELENBP1 protien levels and methanethiol oxidase activity. Evidence supporting this gene-disease relationship includes case-level data and experimental data. At least 2 variants (nonsense and splicing) have been reported in 2 probands from 1 publication (PMID:29255262). Variants in this gene segregated with disease in 1 additional family member. The gene *SELENBP1* encodes an enzyme that serves as a methanethiol oxidase, converting methanethiol, oxygen, and water to formaldehyde, hydrogen sulfide, and hydrogen peroxide. This gene-disease association is further supported by its biochemical function as a methane oxidase in kinetic assays (PMID:29255262) and a knockout mouse model (PMID:29255262) which recapitulates the phenotype of evelated DMS levels in plasma and DMSO2 with decreased Methane Oxidase activity. Additionally, Bulk tissue expression data from the GTEx project demonstrates that *SELENBP1* is primary expressed in the transverse colon, supporting its function as a methane oxidase as methanethiol is produced in the large intestine. Finally, in nonpatient cells, variants of *SELENBP1* were found to have loss and impairment of Methanethiol oxidase function as indicated by little to no detectable H2S and H2O2 generation (PMIDs:33901808, 37437449). In summary, *SELENBP1* is moderately associated with autosomal recessive extraoral halitosis due to methanethiol oxidase deficiency. This gene-disease pair was originally evaluated by the Aminoacidopathy GCEP on November 11, 2022. It was reevaluated on December 6th, 2024. As a result of this reevaluation, new experimental evidence (PMID: 37437449) was added and the classification did not change.
Inheritance Pattern: AR
Disease ID:MONDO:0034186
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0029144
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0029144
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Biochemical
Intervention: General
Rationale: The clinical relevance is unclear
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SELENBP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003944.4. 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 | 1 | 5 | 3 | 9 | ||
| missense | 2 | 78 | 1 | 2 | 83 | |
| nonsense | 2 | 1 | 3 | |||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 10 | 11 | |||
| Total | 1 | 4 | 90 | 6 | 5 | 106 |
Highest pathogenic variant AF is 0.000044609224
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003935.2 | 12 | MANE Select | |
| Ensembl | ENSP00000357861.5 | 12 | MANE Select | |
| RefSeq | NP_001245217.1 | 11 | Standard | |
| RefSeq | NP_001245218.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Selenium Metabolism and Selenoproteins
- IL1 and megakaryocytes in obesity
Biological Process
- protein transport
- oxidation-reduction process
Molecular Function
- protein binding
- selenium binding
- methanethiol oxidase activity
Cellular Component
- fibrillar center
- extracellular space
- nucleolus
- cytosol
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368868
- Coding exons
- 12
- Length
- 8432
- Individuals with no LoFs
- 125700
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 47
- Defined
- 125747
- p
- 0.000187
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.449 | 262 | 283 | 0.925 | 0.0000164 | 3048 |
| Missense (PolyPhen) | 98 | 105.31 | 0.93057 | 1103 | ||
| Synonymous | -0.223 | 119 | 116 | 1.03 | 0.00000719 | 935 |
| Loss of Function | 0.354 | 25 | 27.0 | 0.926 | 0.00000140 | 285 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00086 | 0.00086 | rare |
| Latino/Admixed American | 0.00020 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the oxidation of methanethiol, an organosulfur compound known to be produced in substantial amounts by gut bacteria (PubMed:29255262). Selenium-binding protein which may be involved in the sensing of reactive xenobiotics in the cytoplasm. May be involved in intra-Golgi protein transport (By similarity). {ECO:0000250|UniProtKB:Q8VIF7, ECO:0000269|PubMed:29255262}.;
- Disease
- DISEASE: Note=SELENBP1 mutations are responsible for an autosomal recessive malodor condition characterized by extraoral blood-borne halitosis resulting from the accumulation of sulfur-containing metabolites. In extraoral blood-borne halitosis, malodorant compounds are carried to the lungs, where they enter the breath. Affected individuals have a cabbage-like breath odor, high levels of methanethiol and dimethylsulfide in oral and nasal breath, and elevated urinary excretion of dimethylsulfoxide in the absence of intake of dimethylsulfide-containing food or use of sulfur- containing medication, lower-gastrointestinal problems, and known metabolic defects, such as methionine adenosyltransferase deficiency and tyrosinemia. {ECO:0000269|PubMed:29255262}.;
Intolerance Scores
- LoFtool
- 0.285
- RVIS EVS
- -0.64
- RVIS percentile EVS
- 16.53
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.875
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |