The reference OMIM entry for this protein is 613072

Lipoxygenase homology domain-containing 1; loxhd1

CLONING

Grillet et al. (2009) cloned mouse Loxhd1, and by database analysis, they identified human LOXHD1. They also cloned a splice variant of Loxhd1 from a mouse inner ear cDNA library, which encodes a deduced 2,068-amino acid mouse protein made up of 15 polycystin (see 601313)/lipoxygenase (see 607206)/alpha-toxin (PLAT) domains. PLAT domains are about 120 amino acids long, form a beta-sandwich consisting of 2 sheets of 4 strands each, and appear to function in plasma membrane targeting. Grillet et al. (2009) identified LOXHD1 orthologs in vertebrates, cephalochordates, and urochordates, but not in arthropods or nematode. In situ hybridization detected Loxhd1 expression in the developing mouse inner ear at embryonic days 13.5 and 16, but not in any other tissue. At postnatal day 4, expression was detected in cochlear and vestibular hair cells, with highest concentration in the nucleus. Loxhd1 progressively localized to the cytoplasm, and in the adult, Loxhd1 was expressed in hair cells along the length of stereocilia. Riazuddin et al. (2012) detected expression of LOXHD1 in cultured human corneal endothelial cells. In mouse corneas at postnatal day 120, Loxhd1 was detected both in the corneal epithelium and in the endothelium, but with significantly higher expression in epithelial cells.

GENE STRUCTURE

Based on conservation between the mouse and human LOXHD1 genes, Grillet et al. (2009) determined that the LOXHD1 gene contains at least 43 exons.

MAPPING

By genomic sequence analysis, Grillet et al. (2009) mapped the LOXHD1 gene to chromosome 18q12-q21.

MOLECULAR GENETICS

- Autosomal Recessive Deafness 77 In a 5-generation consanguineous Iranian family with nonsyndromic hearing loss mapping to chromosome 18q12-q21 (DFNB77; 613079), Grillet et al. (2009) sequenced the LOXHD1 gene and identified a homozygous mutation (R670X; 613072.0001) in all affected family members tested. Unaffected family members were heterozygous for the mutation, which was not found in 243 controls. In 9 affected children from 2 unrelated Ashkenazi Jewish families with severe to profound congenital nonprogressive nonsyndromic hearing loss in which linkage to the GJB2 (121011)/GJB6 (604418) genes had been excluded, Edvardson et al. (2011) identified homozygosity for a nonsense mutation in the LOXHD1 gene (R1572X; 613072.0002). - Associations Pending Confirmation For discussion of a possible role of variation in the LOXHD1 gene in Fuchs endothelial corneal dystrophy mapping to chromosome 18q21 (FECD3; 613267), see 613072.0003.

ANIMAL MODEL

Using an N-ethyl-N-nitrosourea (ENU) mutagenesis screen, Grillet et al. (2009) developed the 'samba' mouse line that becomes hearing impaired by 3 weeks of age and deaf by 8 weeks of age. Homozygous samba mice showed no other neurologic or vestibular abnormalities, and heterozygous samba mice appeared completely normal. Stereociliary development was not affected in homozygous samba mice, but hair cell function was perturbed and hair cells eventually degenerated. Grillet et al. (2009) found that samba was a mutation in the mouse Loxhd1 gene that destabilized the beta-sandwich structure of PLAT domain 10. The mutation did not alter mRNA or protein stability or localization of Loxhd1 protein along the length of stereocilia. However, by postnatal day 21, some hair cells showed morphologic defects with fused stereocilia and membrane ruffling at the apical cell surface. Profound deg ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 613072 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).