Alternative titles; symbols
HGNC Approved Gene Symbol: SELENBP1
SNOMEDCT: 1269235004;
Cytogenetic location: 1q21.3 Genomic coordinates (GRCh38) : 1:151,364,304-151,372,705 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1q21.3 | Extraoral halitosis due to MTO deficiency | 618148 | Autosomal recessive | 3 |
The SELENBP1 gene encodes methanethiol oxidase (MTO; EC 1.8.3.4), which converts methanethiol, water, and oxygen to formaldehyde, hydrogen sulfide, and hydrogen peroxide.
Selenium is an essential nutrient that exhibits potent anticarcinogenic properties, and deficiency of selenium may cause certain neurologic diseases. It has been proposed that the effects of selenium in preventing cancer and neurologic diseases may be mediated by selenium-binding proteins. By sequencing randomly selected human fetal heart cDNAs, followed by searching sequence databases for sequence similarities, Chang et al. (1997) identified a cDNA that has sequence similarity to the mouse 56-kD selenium-binding protein (Sp56) gene. The deduced 472-amino acid human SP56 (SELENBP1) has 87.3% and 86.4% amino acid identity to mouse Sp56 and the acetaminophen metabolite-binding protein AP56, respectively. Northern blot analysis of mouse tissues detected the highest Sp56 expression in liver, kidney, and lung (see also Lanfear et al., 1993).
Pol et al. (2018) found that human SELENBP1 mRNA is ubiquitously expressed, with highest expression in adult kidney, duodenum, liver, lung, and brain.
Okunuki et al. (2007) identified selenium-binding protein as a candidate retinal autoantigen in patients with Behcet disease (109650). Because anti-SELENBP1 antibody-positive patients showed more frequent ocular inflammation than the antibody-negative patient group, Okunuki et al. (2007) concluded that autoimmunity against this retinal antigen might contribute to the pathogenesis of uveitis in BD patients.
By FISH, Chang et al. (1997) mapped the SELENBP1 gene to chromosome 1q21-q22.
Pol et al. (2018) identified SELENBP1 as the human methanethiol oxidase (MTO), catalyzing the conversion of methanethiol to formaldehyde, hydrogen sulfide, and hydrogen peroxide. MTO activity is relatively high in erythrocytes, low in leukocytes, and scarcely detectable in plasma.
Pol et al. (2018) identified 4 different pathogenic variants in the SELENBP1 gene in 3 families with autosomal recessive extraoral halitosis due to MTO deficiency. Patients with deficiency of MTO showed elevated methanethiol and dimethylsulfide (DMS) in breath and elevated DMS, dimethylsulfoxide (DMSO), and dimethylsulfone (DMSO2) in blood, cerebrospinal fluid (CSF), and urine. Sibs from a family of Turkish origin were homozygous for a nonsense mutation (604188.0001); a Portuguese patient was homozygous for a splice site mutation (604188.0002); and Dutch sibs carried compound heterozygous missense mutations (604188.0003, 604188.0004).
In 2 sibs from a German family of Turkish origin with extraoral halitosis due to methanethiol oxidase deficiency (EHMTO; 618148), Pol et al. (2018) identified homozygosity for a c.1039G-T transversion (c.1039G-T, NM_003944.3) in the SELENBP1 gene, resulting in the substitution of a premature termination codon for glycine-347 (G347X). The G347X variant was not present in the ExAC database (10/12/2018) (Hamosh, 2018). In addition to mutation in SELENBP1, the affected male in this family, who had additional neurologic features, carried homozygous premature termination mutations in the OR4S2 and THAP4 (612533) genes; Pol et al. (2018) considered mutation in THAP4 possibly responsible for the broader neurologic phenotype in this patient.
In a Portuguese boy with extraoral halitosis due to methanethiol oxidase deficiency (EHMTO; 618148), born of consanguineous parents, Pol et al. (2018) identified homozygosity for a splice site mutation in the SELENBP1 gene, a G-to-A substitution at the +1 position of the 5-prime splice site of intron 5 (c.481+1G-A, NM_003944.3). The c.481+1G-A variant was not present in the ExAC database (10/12/2018) (Hamosh, 2018). This patient was also diagnosed with severely progressive ALS and died at the age of 16.5 years; no mutation in SOD1 (147450) was identified.
In 2 sibs with extraoral halitosis due to methanethiol oxidase deficiency (EHMTO; 618148) from a nonconsanguineous Dutch family, Pol et al. (2018) identified compound heterozygosity for mutations in the SELENBP1 gene: a G-to-T transversion at nucleotide 673 (c.673G-T, NM_003944.3), resulting in a glycine-to-tryptophan substitution at codon 225 (G225W), and a c.985C-T transition resulting in a his329-to-tyr (H329Y) substitution (604188.0004). Neither the G225W nor the H329Y variant was present in the ExAC database (10/12/2018) (Hamosh, 2018).
For discussion of the c.985C-T transition (c.985C-T, NM_003944.3) in the SELENBP1 gene, resulting in a his329-to-tyr (H329Y) substitution, that was found in compound heterozygous state in a patient with extraoral halitosis due to methanethiol oxidase deficiency (EHMTO; 618148) by Pol et al. (2018), see 604188.0003.
Chang, P. W. G., Tsui, S. K. W., Liew, C., Lee, C., Waye, M. M. Y., Fung, K. Isolation, characterization, and chromosomal mapping of a novel cDNA clone encoding human selenium binding protein. J. Cell. Biochem. 64: 217-224, 1997. [PubMed: 9027582] [Full Text: https://doi.org/10.1002/(sici)1097-4644(199702)64:2<217::aid-jcb5>3.0.co;2-#]
Hamosh, A. Personal Communication. Baltimore, Md. 10/12/2018.
Lanfear, J., Fleming, J., Walker, M., Harrison, P. Different patterns of regulation of the genes encoding the closely related 56 kDa selenium- and acetaminophen-binding proteins in normal tissues and during carcinogenesis. Carcinogenesis 14: 335-340, 1993. [PubMed: 8453708] [Full Text: https://doi.org/10.1093/carcin/14.3.335]
Okunuki, Y., Usui, Y., Takeuchi, M., Kezuka, T., Hattori, T., Masuko, K., Nakamura, H., Yudoh, K., Usui, M., Nishioka, K., Kato, T. Proteomic surveillance of autoimmunity in Behcet's disease with uveitis: selenium binding protein is a novel autoantigen in Behcet's disease. Exp. Eye Res. 84: 823-831, 2007. [PubMed: 17343851] [Full Text: https://doi.org/10.1016/j.exer.2007.01.003]
Pol, A., Renkema, G. H., Tangerman, A., Winkel, E. G., Engelke, U. F., de Brouwer, A. P. M., Lloyd, K. C., Araiza, R. S., van den Heuvel, L., Omran, H., Olbrich, H., Oude Elberink, M., and 9 others. Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis. Nature Genet. 50: 120-129, 2018. [PubMed: 29255262] [Full Text: https://doi.org/10.1038/s41588-017-0006-7]