The MKRN3 gene provides instructions for making a protein called makorin ring finger protein 3 (MKRN3). This protein plays a role in directing the onset of puberty, which describes the changes in the body related to sexual development that normally occur in adolescence. Puberty begins when a gland in the brain called the hypothalamus is stimulated to release bursts of a hormone called gonadotropin releasing hormone (GnRH). This hormone triggers the release of other hormones that direct sexual development. Research suggests that the MKRN3 protein blocks (inhibits) the release of GnRH from the hypothalamus, thus holding off the onset of puberty.

The exact function of the MKRN3 protein is unknown. Based on its structure, the protein is thought to play a role in the cell machinery that breaks down (degrades) unwanted proteins, called the ubiquitin-proteasome system, by helping attach a molecule called ubiquitin to unwanted proteins. Ubiquitin acts as a signal to the ubiquitin-proteasome system to break the protein down. Researchers speculate that MKRN3 adds ubiquitin to proteins that would otherwise stimulate GnRH release. The breakdown of such proteins ensures that puberty does not begin until the right time.

For most genes, both copies of the gene (one copy inherited from each parent) are active in all cells. However, the activity of the MKRN3 gene depends on which parent it was inherited from. Only the copy inherited from a person's father is active; the copy inherited from the mother is not active. This sort of parent-specific difference in gene activation is caused by a phenomenon called genomic imprinting.

Tests Listed in the Genetic Testing Registry

• Tests of MKRN3

Scientific Articles on PubMed

• PubMed

Catalog of Genes and Diseases from OMIM

• MAKORIN 3; MKRN3

Gene and Variant Databases

• NCBI Gene
• ClinVar

• Abreu AP, Dauber A, Macedo DB, Noel SD, Brito VN, Gill JC, Cukier P, Thompson IR, Navarro VM, Gagliardi PC, Rodrigues T, Kochi C, Longui CA, Beckers D, de Zegher F, Montenegro LR, Mendonca BB, Carroll RS, Hirschhorn JN, Latronico AC, Kaiser UB. Central precocious puberty caused by mutations in the imprinted gene MKRN3. N Engl J Med. 2013 Jun 27;368(26):2467-75. doi: 10.1056/NEJMoa1302160. Epub 2013 Jun 5. Citation on PubMed or Free article on PubMed Central
• Hagen CP, Sorensen K, Mieritz MG, Johannsen TH, Almstrup K, Juul A. Circulating MKRN3 levels decline prior to pubertal onset and through puberty: a longitudinal study of healthy girls. J Clin Endocrinol Metab. 2015 May;100(5):1920-6. doi: 10.1210/jc.2014-4462. Epub 2015 Feb 19. Citation on PubMed
• Neocleous V, Shammas C, Phelan MM, Nicolaou S, Phylactou LA, Skordis N. In silico analysis of a novel MKRN3 missense mutation in familial central precocious puberty. Clin Endocrinol (Oxf). 2016 Jan;84(1):80-4. doi: 10.1111/cen.12854. Epub 2015 Aug 6. Citation on PubMed
• Simon D, Ba I, Mekhail N, Ecosse E, Paulsen A, Zenaty D, Houang M, Jesuran Perelroizen M, de Filippo GP, Salerno M, Simonin G, Reynaud R, Carel JC, Leger J, de Roux N. Mutations in the maternally imprinted gene MKRN3 are common in familial central precocious puberty. Eur J Endocrinol. 2016 Jan;174(1):1-8. doi: 10.1530/EJE-15-0488. Epub 2015 Oct 1. Citation on PubMed