Alternative titles; symbols
HGNC Approved Gene Symbol: NXNL1
Cytogenetic location: 19p13.11 Genomic coordinates (GRCh38) : 19:17,455,425-17,460,926 (from NCBI)
By expression cloning using a viability assay based on cone-enriched primary cultures from chicken embryos to isolate factors that could support cone survival, Leveillard et al. (2004) identified Nxnl1, which they called Rdcvf, a truncated thioredoxin-like protein specifically expressed in photoreceptors. Rdcvf has 33% similarity to thioredoxin (TXN; 187700). The Rdcvf protein contains a potential N-glycosylation site and lacks a signal peptide sequence. The C terminus of Rdcvf interrupts the thioredoxin motif, and unlike other members of the thioredoxin family, Rdcvf did not have detectable oxidoreductase activity; however, an alternatively spliced form of Rdcvf mRNA results in a longer protein with a C-terminal extension and could have oxidoreductase activity. Leveillard et al. (2004) suggested that Rdcvf may be a bifunctional protein, with one extracellular form involved in cone viability and the other, with the extended C terminus, having oxidoreductase activity. Factors secreted from rods have been shown to be essential for cone viability (see Fintz et al., 2003). As cone loss is responsible for the main visual handicap in retinitis pigmentosa (RP; 268000), the identification of the Rdcvf protein was seen by Leveillard et al. (2004) as presenting new treatment possibilities for RP.
Chalmel et al. (2007) identified NXNL1 genes predicted to encode long and short NXNL1 variants, which they called RDCVFL and RDCVFS, respectively, in most vertebrates examined. Human RDCVFL contains 212 amino acids and, like the mouse protein, has a predicted C-terminal thioredoxin-like domain that is absent in the predicted RDCVFS isoform.
Reichman et al. (2010) identified the homeodomain proteins CHX10/VSX2 (142993), VSX1 (605020), and PAX4 (167413), as well as the zinc finger protein SP3 (601804), as factors that could stimulate both the mouse and human NXNL1 promoter. In addition, CHX10/VSX2 bound to the NXNL1 promoter in vivo. Rdcvf was expressed in the inner as well as the outer retina of mice. The loss of rods in the rd1 mouse, a model of retinitis pigmentosa, was associated with decreased expression of Rdcvf by inner retinal cells as well as by rods. Reichman et al. (2010) proposed an alternative therapeutic strategy aimed at recapitulating RDCVF expression in the inner retina, where cell loss is not significant, to prevent secondary cone death and central vision loss in patients suffering from retinitis pigmentosa.
Chalmel et al. (2007) determined that the NXNL1 gene contains 2 exons.
Hartz (2013) mapped the NXNL1 gene to chromosome 19p13.11 based on an alignment of the NXNL1 sequence (GenBank BC014127) with the genomic sequence (GRCh37).
Chalmel et al. (2007) mapped the mouse Nxnl1 gene to chromosome 8.
Chalmel, F., Leveillard, T., Jaillard, C., Lardenois, A., Berdugo, N., Morel, E., Koehl, P., Lambrou, G., Holmgren, A., Sahel, J. A., Poch, O. Rod-derived cone viability factor-2 is a novel bifunctional-thioredox in-like protein with therapeutic potential. BMC Molec. Biol. 8: 74, 2007. Note: Electronic Article. [PubMed: 17764561] [Full Text: https://doi.org/10.1186/1471-2199-8-74]
Fintz, A. C., Audo, I., Hicks, D., Mohand-Said, S., Leveillard, T., Sahel, J. Partial characterization of retina-derived cone neuroprotection in two culture models of photoreceptor degeneration. Invest. Ophthal. Vis. Sci. 44: 818-825, 2003. [PubMed: 12556418] [Full Text: https://doi.org/10.1167/iovs.01-1144]
Hartz, P. A. Personal Communication. Baltimore, Md. 7/10/2013.
Leveillard, T., Mohand-Said, S., Lorentz, O., Hicks, D., Fintz, A.-C., Clerin, E., Simonutti, M., Forster, V., Cavusoglu, N., Chalmel, F., Dolle, P., Poch, O., Lambrou, G., Sahel, J.-A. Identification and characterization of rod-derived cone viability factor. Nature Genet. 36: 755-759, 2004. [PubMed: 15220920] [Full Text: https://doi.org/10.1038/ng1386]
Reichman, S., Kalathur, R. K. R., Lambard, S., Ait-Ali, N., Yang, Y., Lardenois, A., Ripp, R., Poch, O., Zack, D. J., Sahel, J.-A., Leveillard, T. The homeobox gene CHX10/VSX2 regulates RdCVF promoter activity in the inner retina. Hum. Molec. Genet. 19: 250-261, 2010. [PubMed: 19843539] [Full Text: https://doi.org/10.1093/hmg/ddp484]