Alternative titles; symbols
HGNC Approved Gene Symbol: NRTN
Cytogenetic location: 19p13.3 Genomic coordinates (GRCh38): 19:5,805,067-5,828,324 (from NCBI)
Neurturin, a potent neurotrophic factor, was purified from Chinese hamster ovary cell-conditioned media by Kotzbauer et al. (1996). It is closely related to glial cell line-derived neurotrophic factor (GDNF; 600837). NRTN and GDNF form a distinct TGF-beta subfamily, referred to as TRNs (for 'TGF-beta-related neurotrophins'). GDNF is a ligand for the tyrosine kinase receptor RET (164761). Signaling requires an additional GPI-linked protein, GDNF receptor-alpha (GDNFRA; 601496). NRTN also signals through RET and a GPI-linked coreceptor. Like GDNF, neurturin can promote the survival of numerous neuronal populations, including sympathetic, nodose, and dorsal root ganglion sensory neurons. Heuckeroth et al. (1997) isolated mouse and human genomic neurturin clones.
Heuckeroth et al. (1997) determined that preproneurturin is encoded by 2 exons. Mouse and human clones had common intron/exon boundaries.
Heuckeroth et al. (1997) used interspecific backcross analysis to localize neurturin to mouse chromosome 17 and fluorescence in situ hybridization to localize human neurturin to the syntenic region of 19p13.3.
Considering that RET and GDNF mutations had been reported in Hirschsprung disease, Doray et al. (1998) regarded the other RET ligand, neurturin, as an attractive candidate gene, especially as it shares large homologies with GDNF. Doray et al. (1998) reported a heterozygous missense NTN mutation in a large nonconsanguineous family including 4 children affected with a severe aganglionosis phenotype extending up to the small intestine. It appeared that the NTN mutation they found was not sufficient to cause HSCR, and this multiplex family also segregated a RET mutation (164761.0035). Doray et al. (1998) concluded that this cascade of independent and additive genetic events fits well with the multigenic pattern of inheritance expected in HSCR, and further supports the role of RET ligands in the development of the enteric nervous system.
Doray, B., Salomon, R., Amiel, J., Pelet, A., Touraine, R., Billaud, M., Attie, T., Bachy, B., Munnich, A., Lyonnet, S. Mutation of the RET ligand, neurturin, supports multigenic inheritance in Hirschsprung disease. Hum. Molec. Genet. 7: 1449-1452, 1998. Note: Erratum: Hum. Molec. Genet. 7: 1831 only, 1998. [PubMed: 9700200] [Full Text: https://doi.org/10.1093/hmg/7.9.1449]
Heuckeroth, R. O., Kotzbauer, P., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Zimonjic, D. B., Popescu, N. C., Johnson, E. M., Jr., Milbrandt, J. Neurturin, a novel neurotrophic factor, is localized to mouse chromosome 17 and human chromosome 19p13.3. Genomics 44: 137-140, 1997. [PubMed: 9286710] [Full Text: https://doi.org/10.1006/geno.1997.4846]
Kotzbauer, P. T., Lampe, P. A., Heuckeroth, R. O., Golden, J. P., Creedon, D. J., Johnson, E. M., Jr., Milbrandt, J. Neurturin, a relative of glial-cell-line-derived neurotrophic factor. Nature 384: 467-470, 1996. [PubMed: 8945474] [Full Text: https://doi.org/10.1038/384467a0]