HGNC Approved Gene Symbol: EPHA10
Cytogenetic location: 1p34.3 Genomic coordinates (GRCh38): 1:37,713,880-37,765,120 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1p34.3 | ?Deafness, autosomal dominant 88 | 620283 | Autosomal dominant | 3 |
Ephrin receptors, the largest subfamily of receptor tyrosine kinases (RTKs), and their ephrin ligands are important mediators of cell-cell communication regulating cell attachment, shape, and mobility in neuronal and epithelial cells (Aasheim et al., 2005). See 179610 for additional background on Eph receptors and ephrins.
By database analysis, Robinson et al. (2000) identified EPHA10. By further database analysis and PCR of a testis cDNA library, Aasheim et al. (2005) cloned EPHA10 and identified 3 isoforms. A 295-amino acid soluble secreted Eph receptor (EphA10s) contains the Eph receptor ligand-binding domain but lacks fibronectin III repeats. Full-length EphA10 is composed of 1008 predicted amino acids, the first 283 of which are identical to EphA10s, and its sequence predicts the canonic Eph receptor structure containing an Eph ligand-binding domain, 2 fibronectin III repeats, an intracellular conserved kinase domain, and a SAM domain. The third isoform, EphA10*, lacks the SAM domain. EPHA10 shares 91% amino acid identity with its mouse ortholog. Northern blot analysis of human tissues detected expression in testis only. Binding studies with EphA10s showed strong binding to EFNA3 (601381), EFNA4 (601380) and EFNA5 (601535), but weak binding to EFNB1 (300035) and EFNB2 (600527).
By RT-PCR and Western blot in mouse cochlea, Huang et al. (2023) observed expression of Epha10. Immunohistochemistry and immunofluorescence confirmed expression and demonstrated wide distribution of Epha10 in the organ of Corti, spiral ganglion, and stria vascularis.
Aasheim et al. (2005) determined that the EPHA10 gene contains 17 exons. Alternative splicing of exons 3 and 15 results in a soluble isoform EphA10s, which contains only the first 3 exons, and an isoform lacking the SAM domain, which they called EphA10*.
Aasheim et al. (2005) noted that the EPHA10 gene maps to chromosome 1p34.3.
In a large 4-generation Han Chinese family with autosomal dominant nonsyndromic postlingual profound deafness mapping to 1p34 (DFNA88; 620283), Huang et al. (2023) identified heterozygosity for a deletion/insertion in the 5-prime UTR of the EPHA10 gene (611123.0001) that segregated fully with disease and was not found in public variant databases. Patient cells showed upregulation of EPHA10 compared to controls.
Huang et al. (2023) created fly models of Eph overexpression in the Drosophila melanogaster chordotonal organ (Johnston organ), which senses sound as well as gravity and wind. Immunofluorescence staining demonstrated a looser and less orderly arrangement of the scolopale rods than in control flies. In addition, the Eph-overexpressed flies exhibited poorer performance on negative geotaxis assays, suggesting that both structural and functional changes in the Johnston organ resulted from overexpression of Eph.
In a large 4-generation Han Chinese family with autosomal dominant nonsyndromic postlingual profound deafness mapping to 1p34 (DFNA88; 620283), originally described by Jiang et al. (2011), Huang et al. (2023) identified heterozygosity for a deletion/insertion (c.-81_-73delinsAGC, NM_001099439.1) within the highly conserved 5-prime UTR of the EPHA10 gene. Sanger sequencing confirmed the mutation, which segregated fully with disease in the family and was not found in the 1000 Genomes Project, ExAC, or gnomAD databases. Analysis of patient lymphoblastoid cell lines by qRT-PCR and Western blot revealed upregulation of EPHA10 compared to control cells.
Aasheim, H.-C., Patzke, S., Hjorthaug, H. S., Finne, E. F. Characterization of a novel Eph receptor tyrosine kinase, EphA10, expressed in testis. Biochem. Biophys. Acta 1723: 1-7, 2005. [PubMed: 15777695] [Full Text: https://doi.org/10.1016/j.bbagen.2005.01.011]
Huang, S., Ma, L., Liu, X., He, C., Li, J., Hu, Z., Jiang, L., Liu, Y., Liu, X., Feng, Y., Cai, X. A non-coding variant in 5-prime untranslated region drove up-regulation of pseudo-kinase EPHA10 and caused non-syndromic hearing loss in humans. Hum. Molec. Genet. 32: 720-731, 2023. [PubMed: 36048850] [Full Text: https://doi.org/10.1093/hmg/ddac223]
Jiang, L., Liu, Y., Feng, Y., Hu, Z., Mei, L., Long, L., Chen, H., Xue, J., Xia, K., He, C. Gene localization in a Chinese family with autosomal dominant non-syndromic deafness. Acta Otolaryng. 131: 1061-1068, 2011. [PubMed: 21651318] [Full Text: https://doi.org/10.3109/00016489.2011.591822]
Robinson, D. R., Wu, Y.-M., Lin, S.-F. The protein tyrosine kinase family of the human genome. Oncogene 19: 5548-5557, 2000. [PubMed: 11114734] [Full Text: https://doi.org/10.1038/sj.onc.1203957]