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.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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