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LRTOMT
Protein-coding gene in the species Homo sapiens From Wikipedia, the free encyclopedia
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Leucine rich transmembrane and O-methyltransferase domain containing is a protein that is encoded by the LRTOMT gene in humans. This locus represents naturally occurring read-through transcript between the neighboring LRRC51 (leucine-rich repeat containing 51) and TOMT (transmembrane O-methyltransferase) genes on chromosome 11. Mutations in LRTOMT are associated with the DFNB63 form of autosomal recessive nonsyndromic hearing loss.
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Gene
LRTOMT is a fusion between the LRRC51 and TOMT genes in humans. The fusion gene contains 10 exons that encode two separate proteins translated from unique and overlapping open reading frames (ORFs). Translation of LRTOMT1, a protein that contains leucine-rich repeats, starts in exon 3 and stops at exon 6. Translation of LRTOMT2, also known as TOMT or COMT2, starts in exon 5 and ends at exon 10. Human TOMT has a predicted methyltransferase domain that is conserved with catechol-o-methyltransferase (COMT) and a single predicted transmembrane alpha helix. Mice and zebrafish have separate genes for Lrrc51 and Tomt.[5]
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Function
TOMT is required for cochlear hair cell function and is associated with components of the mechanoelectrical transduction (MET) channel, including TMC1. While the mechanism by which TOMT contributes to MET currents and auditory function is currently unknown, the methyltransferase domain is likely not involved. Mutations in TOMT disrupt the stereocilia localization of MET channel subunits and are thus thought to affect MET currents. These results have also been illustrated in multiple mutations in both mice and zebrafish.[6][7]
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Clinical significance
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Over 20 variants in TOMT have been shown to cause hearing loss in humans. Populations reported to be most affected by TOMT-related hearing loss include Iranian and Tunisian families.[8]
While most variations cause prelingual profound sensorineural deafness, one patient with compound heterozygous mutations (Arg52Trp and Arg54Gln) was reported to develop ski-slope hearing loss starting at age 11.[9]
TOMT has also been associated with postmenopausal osteoporosis in rats. Specifically, LRTOMT downregulation after ovariectomy was significantly correlated with decreased bone density and changes in bone microstructure.[10]
References
Further reading
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