PROKR2

PROKINETICIN RECEPTOR 2

• OMIM 607123
• Located at chromosome 20p12.3
• Encodes the G protein-coupled prokineticin receptor 2.
• PROKR2 comprises 3 exons and the corresponding mRNA (NM_144773.2) encodes a 384 amino acid protein.

Human genetics

• Mutations in PROKR2 cause congenital hypogonadotropic hypogonadism with (Kallmann syndrome) or without anosmia and are spread throughout the gene (Dode, Teixeira et al. 2006; (Balasubramanian, Dwyer et al. 2010).

• Most mutations of PROKR2 are missense mutations found in the heterozygous state in most patients. Several PROKR2 mutations (those marked with*) have, however, been found in both the heterozygous and homozygous (or compound heterozygous) states suggesting that patients heterozygous for PROKR2 mutations carry additional mutations, presumably in other, as yet unidentified Kallmann syndrome genes in most cases (Dode, Teixeira et al. 2006; Sarfati, Guiochon-Mantel et al. 2010).

Animal models

Prokr2 knockout mice have hypoplasia of the olfactory bulbs and reproductive organs. Immunohistochemical analysis revealed that GnRH neurons were absent in the hypothalamus (Matsumoto, Yamazaki et al. 2006).

References

Balasubramanian, R., A. Dwyer, et al. (2010). "Human GnRH deficiency: a unique disease model to unravel the ontogeny of GnRH neurons." Neuroendocrinology92(2): 81-99.

Dode, C., L. Teixeira, et al. (2006). "Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2." PLoS Genet2(10): e175.

Matsumoto, S., C. Yamazaki, et al. (2006). "Abnormal development of the olfactory bulb and reproductive system in mice lacking prokineticin receptor PKR2." Proc Natl Acad Sci U S A103(11): 4140-4145.

Sarfati, J., A. Guiochon-Mantel, et al. (2010). "A comparative phenotypic study of kallmann syndrome patients carrying monoallelic and biallelic mutations in the prokineticin 2 or prokineticin receptor 2 genes." J Clin Endocrinol Metab95(2): 659-669.