Normal Function
The ATP2A1 gene provides instructions for making an enzyme called sarco(endo)plasmic reticulum calcium-ATPase 1 (SERCA1). This enzyme belongs to a family of ATPase enzymes that help control the level of positively charged calcium atoms (calcium ions) inside cells. The SERCA1 enzyme is found in skeletal muscle cells. (Skeletal muscles are the muscles used for movement.) Within muscle cells, the SERCA1 enzyme is located in the membrane of a structure called the sarcoplasmic reticulum. This structure plays a major role in muscle contraction and relaxation by storing and releasing calcium ions. When calcium ions are transported out of the sarcoplasmic reticulum, muscles contract; when calcium ions are transported into the sarcoplasmic reticulum, muscles relax. The SERCA1 enzyme transports calcium ions from the cell into the sarcoplasmic reticulum, triggering muscle relaxation.
Health Conditions Related to Genetic Changes
Brody myopathy
At least 10 mutations in the ATP2A1 gene have been found to cause Brody myopathy, a muscle disorder characterized by muscle cramping after exercise. Most ATP2A1 gene mutations lead to a premature stop signal in the instructions for making the SERCA1 enzyme, resulting in a nonfunctional enzyme. Other mutations lead to the production of a SERCA1 enzyme with decreased function. As a result, calcium ions are slow to enter the sarcoplasmic reticulum and muscle relaxation is delayed. After exercise or other strenuous activity, during which the muscles rapidly contract and relax, people with Brody myopathy develop muscle cramps because their muscles cannot fully relax. Scientists believe that other proteins or other pathways may function in the absence of a fully functional SERCA1 enzyme to transport calcium ions into the sarcoplasmic reticulum and help with muscle relaxation.
More About This Health ConditionOther Names for This Gene
- AT2A1_HUMAN
- ATP2A
- ATPase, Ca++ transporting, cardiac muscle, fast twitch 1
- calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform 1
- endoplasmic reticulum class 1 Ca2+ ATPase
- sarcoplasmic/endoplasmic reticulum calcium ATPase 1
- SERCA1
- SR Ca2+ ATPase 1
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Odermatt A, Taschner PE, Khanna VK, Busch HF, Karpati G, Jablecki CK, Breuning MH, MacLennan DH. Mutations in the gene-encoding SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase, are associated with Brody disease. Nat Genet. 1996 Oct;14(2):191-4. doi: 10.1038/ng1096-191. Citation on PubMed
- Shull GE, Okunade G, Liu LH, Kozel P, Periasamy M, Lorenz JN, Prasad V. Physiological functions of plasma membrane and intracellular Ca2+ pumps revealed by analysis of null mutants. Ann N Y Acad Sci. 2003 Apr;986:453-60. doi: 10.1111/j.1749-6632.2003.tb07229.x. Citation on PubMed
- Vattemi G, Gualandi F, Oosterhof A, Marini M, Tonin P, Rimessi P, Neri M, Guglielmi V, Russignan A, Poli C, van Kuppevelt TH, Ferlini A, Tomelleri G. Brody disease: insights into biochemical features of SERCA1 and identification of a novel mutation. J Neuropathol Exp Neurol. 2010 Mar;69(3):246-52. doi: 10.1097/NEN.0b013e3181d0f7d5. Citation on PubMed
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