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Normal Function
The GALNT3 gene provides instructions for making a protein called ppGalNacT3, which is found in many types of cells. This protein plays a major role in regulating phosphate levels within the body (phosphate homeostasis). Among its many functions, phosphate plays a critical role in the formation and growth of bones in childhood and helps maintain bone strength in adults. Phosphate levels are controlled in large part by the kidneys. The kidneys normally rid the body of excess phosphate by excreting it in urine, and they reabsorb this mineral into the bloodstream when more is needed.
The ppGalNacT3 protein regulates the activity of a protein called fibroblast growth factor 23, which is produced in bone cells and whose function is to signal the body to decrease phosphate reabsorption by the kidneys. The ppGalNacT3 protein attaches sugar molecules to particular regions of fibroblast growth factor 23 through a process called glycosylation. These sugar molecules are required for the protein's transport out of cells and to protect the protein from being broken down. When phosphate levels are increased, ppGalNacT3 glycosylates fibroblast growth factor 23 so it will not be broken down. Signaling from fibroblast growth factor 23 leads to a decrease in phosphate reabsorption, which helps to maintain normal phosphate levels in the body.
Health Conditions Related to Genetic Changes
Hyperphosphatemic familial tumoral calcinosis
At least 25 mutations in the GALNT3 gene have been found to cause hyperphosphatemic familial tumoral calcinosis (HFTC), a condition characterized by an increase in the levels of phosphate in the blood (hyperphosphatemia) and abnormal deposits of phosphate and calcium (calcinosis) in the body's tissues. GALNT3 gene mutations result in the production of ppGalNacT3 protein with little or no function. As a result, ppGalNacT3 cannot glycosylate fibroblast growth factor 23. Fibroblast growth factor 23 becomes trapped within the cell and is broken down rather than being released from cells (secreted) as usual. Without fibroblast growth factor 23, more phosphate is reabsorbed back into the bloodstream by the kidneys, leading to hyperphosphatemia. Calcinosis results when the excess phosphate combines with calcium to form deposits that build up in soft tissues.
More About This Health ConditionOther Names for This Gene
- GalNAc transferase 3
- GalNAc-T3
- GALT3_HUMAN
- polypeptide GalNAc transferase 3
- polypeptide GalNAc-transferase T3
- pp-GaNTase 3
- protein-UDP acetylgalactosaminyltransferase 3
- UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 3
- UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GalNAc-T3)
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Chefetz I, Kohno K, Izumi H, Uitto J, Richard G, Sprecher E. GALNT3, a gene associated with hyperphosphatemic familial tumoral calcinosis, is transcriptionally regulated by extracellular phosphate and modulates matrix metalloproteinase activity. Biochim Biophys Acta. 2009 Jan;1792(1):61-7. doi: 10.1016/j.bbadis.2008.09.016. Epub 2008 Oct 11. Citation on PubMed or Free article on PubMed Central
- Chefetz I, Sprecher E. Familial tumoral calcinosis and the role of O-glycosylation in the maintenance of phosphate homeostasis. Biochim Biophys Acta. 2009 Sep;1792(9):847-52. doi: 10.1016/j.bbadis.2008.10.008. Epub 2008 Oct 25. Citation on PubMed or Free article on PubMed Central
- Farrow EG, Imel EA, White KE. Miscellaneous non-inflammatory musculoskeletal conditions. Hyperphosphatemic familial tumoral calcinosis (FGF23, GALNT3 and alphaKlotho). Best Pract Res Clin Rheumatol. 2011 Oct;25(5):735-47. doi: 10.1016/j.berh.2011.10.020. Citation on PubMed or Free article on PubMed Central
- Ichikawa S, Baujat G, Seyahi A, Garoufali AG, Imel EA, Padgett LR, Austin AM, Sorenson AH, Pejin Z, Topouchian V, Quartier P, Cormier-Daire V, Dechaux M, Malandrinou FCh, Singhellakis PN, Le Merrer M, Econs MJ. Clinical variability of familial tumoral calcinosis caused by novel GALNT3 mutations. Am J Med Genet A. 2010 Apr;152A(4):896-903. doi: 10.1002/ajmg.a.33337. Citation on PubMed or Free article on PubMed Central
- Sprecher E. Familial tumoral calcinosis: from characterization of a rare phenotype to the pathogenesis of ectopic calcification. J Invest Dermatol. 2010 Mar;130(3):652-60. doi: 10.1038/jid.2009.337. Epub 2009 Oct 29. Citation on PubMed or Free article on PubMed Central
- Yancovitch A, Hershkovitz D, Indelman M, Galloway P, Whiteford M, Sprecher E, Kilic E. Novel mutations in GALNT3 causing hyperphosphatemic familial tumoral calcinosis. J Bone Miner Metab. 2011 Sep;29(5):621-5. doi: 10.1007/s00774-011-0260-1. Epub 2011 Feb 25. Citation on PubMed
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