This website was created as an assignment for Genetics 564 at the University of Wisconsin-Madison
RYR2 Gene
The RYR2 gene is located on the first chromosome at position 43. It contains 791,778 base pairs and 105 exons[1,3]. Once processed and introns are spliced out, the mRNA sequence contains 16,365 base pairs and codes a 4967 amino acid protein called the Ryanodine Receptor 2 protein. Gene expression is localized to cardiac myometrium tissue or heart muscle cells and expression has been seen as early as cardiac development in utero[2]. The Ryanodine receptor 2 protein is present in the sacroplasmic reticulum and is responsible for shuttling calcium ions back and forth across the membrane of this organelle[1]. It works together as a tetrad of Ryanodine Receptor 2 proteins to create the calcium ion channel of the tissue. This calcium channel pumps ions back and forth between the sacroplasmic reticulum and the cytoplasm and works in collaboration with potassium and sodium channels to create an ion gradient that produces both contraction and relaxation of the heart[3]. A defective Ryanodine Receptor 2 protein causes a leaky calcium ion channel and leads to a CPVT phenotype[1,3]. The CPVT phenotype is inherited autosomal dominantly, affecting both the male and female genders equally and is inherited at a 50% rate[2].
Single Nucleotide Polymorphisms
A single nucleotide polymorphism (SNP) is a mutation that occurs at only one nucleotide in a sequence. A change in a single nucleotide can disrupt the codon that is responsible for coding a specific amino acid. Due to the variety of shape and function of amino acids, one SNP can be very detrimental. Protein function and folding processes depend heavily of amino-amino interactions within the polypeptide and thus one miscoded amino acid can result in a defective protein. This is exactly what happens in RYR2 gene. There have been over 70 SNPs discovered in the RYR2 gene that produce the CPVT phenotype[1]. These mutations don't cause a complete loss of function of the protein, but instead create a partially functional Ryanodine Receptor that is leaky. These mutations are responsible for 50-65% of cases of CPVT [2].
References:
[1]Ryr2 ryanodine receptor 2 (cardiac) homo sapiens. (2014). Electronic References. Retrieved February 14,2014 from
http://www.ncbi.nlm.nih.gov/gene?cmd=retrieve&list_uids=6262
[2] Gene Reviews. (2013). Electronic references. Retrieved January 31, 2014, from
http://www.ncbi.nlm.nih.gov/books/NBK1289/
[3]OMIM. (2011). Electronic References. Retrieved January 28, 2014 from http://www.omim.org/entry/180902
[1]Ryr2 ryanodine receptor 2 (cardiac) homo sapiens. (2014). Electronic References. Retrieved February 14,2014 from
http://www.ncbi.nlm.nih.gov/gene?cmd=retrieve&list_uids=6262
[2] Gene Reviews. (2013). Electronic references. Retrieved January 31, 2014, from
http://www.ncbi.nlm.nih.gov/books/NBK1289/
[3]OMIM. (2011). Electronic References. Retrieved January 28, 2014 from http://www.omim.org/entry/180902
Site created by: Mercede Davis
Email contact: [email protected]
Date last updated: 5/14/14
Genetics 564, University of Wisconsin-Madison
Email contact: [email protected]
Date last updated: 5/14/14
Genetics 564, University of Wisconsin-Madison