LRTOMT

LRTOMT
Identifiers
Aliases	LRTOMT, CFAP111, DFNB63, LRRC51, leucine rich transmembrane and O-methyltransferase domain containing, TOMT, LRRC51-TOMT
External IDs	OMIM: 612414; MGI: 3769724; HomoloGene: 19664; GeneCards: LRTOMT; OMA:LRTOMT - orthologs
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q13.4 Start 72,080,331 bp[1] End 72,110,782 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 E2|7 Start 101,547,577 bp[2] End 101,555,566 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle right testis left testis olfactory zone of nasal mucosa ganglionic eminence stromal cell of endometrium uterine tube islet of Langerhans gonad ventricular zone Top expressed in morula embryo granulocyte blastocyst primary oocyte epiblast white adipose tissue placenta ovary proximal tubule More reference expression data BioGPS n/a
Gene ontology Molecular function methyltransferase activity transferase activity O-methyltransferase activity L-dopa O-methyltransferase activity catechol O-methyltransferase activity orcinol O-methyltransferase activity Cellular component cytoplasm integral component of membrane membrane plasma membrane endoplasmic reticulum cellular component Biological process methylation hearing catecholamine metabolic process neurotransmitter catabolic process catecholamine catabolic process auditory receptor cell development developmental process dopamine metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 220074 791260 Ensembl ENSG00000284922 ENSMUSG00000078630 UniProt Q8WZ04 Q96E66 A1Y9I9 RefSeq (mRNA) NM_001145308 NM_001145309 NM_001145310 NM_001081679 NM_001282088 RefSeq (protein) NP_001138779 NP_001138780 NP_001138781 NP_001138782 NP_001192067 NP_001258400 NP_001305732 NP_660352 NP_001138779.1 NP_001192067.1 NP_001258400.1 NP_660352.1 NP_001305732.1 NP_001075148 NP_001269017 Location (UCSC) Chr 11: 72.08 – 72.11 Mb Chr 7: 101.55 – 101.56 Mb PubMed search [3] [4]
Wikidata
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Transmembrane O-methyltransferase (TOMT) is a protein encoded by the LRTOMT gene in humans. Located on chromosome 11, mutations in LRTOMT are associated with the DFNB63 form of autosomal recessive nonsyndromic hearing loss.

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]

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]

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]