PROK2

PROKINETICIN 2

• OMIM 607002
• Located at chromosome 3p21.1
• Encodes prokineticin 2, a G protein-coupled receptor ligand
• PROK2 comprises 4 exons (exon 3 undergoing alternative splicing) and encodes the corresponding mRNA (NM_001126128.13). The mature form (signal peptide processed) contains 81 amino acids.

Human genetics

• Mutations in PROK2 cause congenital hypogonadotropic hypogonadism with (Kallmann syndrome) or without anosmia and are spread throughout the gene (Dode, Teixeira et al. 2006; Pitteloud, Zhang et al. 2007; Cole, Sidis et al. 2008; Chan, Broder-Fingert et al. 2009; Dode and Hardelin 2009).

• Most mutations of PROK2 are missense mutations. The mutations are found in the heterozygous state in most patients. Several PROK2 mutations have, however, been found in both the heterozygous and homozygous (or compound heterozygous) states, suggesting that patients heterozygous for PROK2 mutations carry additional mutations, presumably in other, as yet unidentified Kallmann syndrome genes in most cases (Sarfati, Guiochon-Mantel et al. 2010).

Animal models

• Prok2 knockout mice have olfactory bulb defects, defective GnRH neuron migration, and reproductive abnormalities (Pitteloud, Zhang et al. 2007)

References

Chan, Y. M., S. Broder-Fingert, et al. (2009). "Reproductive functions of kisspeptin and Gpr54 across the life cycle of mice and men." Peptides30(1): 42-48.

Cole, L. W., Y. Sidis, et al. (2008). "Mutations in prokineticin 2 and prokineticin receptor 2 genes in human gonadotrophin-releasing hormone deficiency: molecular genetics and clinical spectrum." J Clin Endocrinol Metab93(9): 3551-3559.

Dode, C. and J. P. Hardelin (2009). "Kallmann syndrome." Eur J Hum Genet17(2): 139-146.

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

Pitteloud, N., C. Zhang, et al. (2007). "Loss-of-function mutation in the prokineticin 2 gene causes Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism." Proc Natl Acad Sci U S A104(44): 17447-17452.

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