Health Conditions Related to Genetic Changes
Kallmann syndrome
At least 16 mutations in the PROK2 gene have been identified in people with Kallmann syndrome, a disorder characterized by the combination of hypogonadotropic hypogonadism (a condition affecting the production of hormones that direct sexual development) and an impaired sense of smell. Researchers estimate that mutations in the PROK2 and PROKR2 genes together account for about 9 percent of all cases of Kallmann syndrome.
Most of the PROK2 gene mutations that cause Kallmann syndrome change single protein building blocks (amino acids) in prokineticin 2. These mutations disrupt the protein's activity, affecting its ability to bind to its receptor to send signals normally. Studies suggest that a loss of this signaling disrupts the migration and survival of olfactory neurons and GnRH-producing neurons in the developing brain. If olfactory nerve cells do not extend to the olfactory bulb, a person's sense of smell will be impaired or absent. Misplacement or premature loss of GnRH-producing neurons prevents the production of sex hormones, which interferes with normal sexual development and causes puberty to be delayed or absent.
Because the features and severity of Kallmann syndrome vary among individuals, researchers believe that additional genetic and environmental factors may be involved. Some affected individuals have mutations in one of several other genes in addition to PROK2, and these genetic changes may contribute to the varied features of the condition.
More About This Health ConditionOther Names for This Gene
- BV8
- KAL4
- MIT1
- PK2
- PROK2_HUMAN
- Protein Bv8 homolog
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Balasubramanian R, Crowley WF Jr. Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency. 2007 May 23 [updated 2022 May 12]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1334/ Citation on PubMed
- Cheng MY, Bullock CM, Li C, Lee AG, Bermak JC, Belluzzi J, Weaver DR, Leslie FM, Zhou QY. Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus. Nature. 2002 May 23;417(6887):405-10. doi: 10.1038/417405a. Citation on PubMed
- Dode C, Rondard P. PROK2/PROKR2 Signaling and Kallmann Syndrome. Front Endocrinol (Lausanne). 2013 Apr 12;4:19. doi: 10.3389/fendo.2013.00019. eCollection 2013. Citation on PubMed or Free article on PubMed Central
- Dode C, Teixeira L, Levilliers J, Fouveaut C, Bouchard P, Kottler ML, Lespinasse J, Lienhardt-Roussie A, Mathieu M, Moerman A, Morgan G, Murat A, Toublanc JE, Wolczynski S, Delpech M, Petit C, Young J, Hardelin JP. Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. PLoS Genet. 2006 Oct 20;2(10):e175. doi: 10.1371/journal.pgen.0020175. Epub 2006 Sep 1. Citation on PubMed or Free article on PubMed Central
- Moya-Plana A, Villanueva C, Laccourreye O, Bonfils P, de Roux N. PROKR2 and PROK2 mutations cause isolated congenital anosmia without gonadotropic deficiency. Eur J Endocrinol. 2012 Dec 10;168(1):31-7. doi: 10.1530/EJE-12-0578. Print 2013 Jan. Citation on PubMed
- Ng KL, Li JD, Cheng MY, Leslie FM, Lee AG, Zhou QY. Dependence of olfactory bulb neurogenesis on prokineticin 2 signaling. Science. 2005 Jun 24;308(5730):1923-7. doi: 10.1126/science.1112103. Citation on PubMed
- Pitteloud N, Zhang C, Pignatelli D, Li JD, Raivio T, Cole LW, Plummer L, Jacobson-Dickman EE, Mellon PL, Zhou QY, Crowley WF Jr. Loss-of-function mutation in the prokineticin 2 gene causes Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17447-52. doi: 10.1073/pnas.0707173104. Epub 2007 Oct 24. Citation on PubMed or Free article on PubMed Central
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