1. Normal Function
The GALE gene provides instructions for making an enzyme called UDP-galactose-4-epimerase. This enzyme enables the body to process a simple sugar called galactose, which is present in small amounts in many foods. Galactose is primarily part of a larger sugar called lactose, which is found in all dairy products and many baby formulas.
UDP-galactose-4-epimerase converts a modified form of galactose (UDP-galactose) to another modified sugar (UDP-glucose). Glucose is a simple sugar that is the main energy source for most cells. This enzyme also promotes the reverse chemical reaction, the conversion of UDP-glucose to UDP-galactose. UDP-galactose is used to build galactose-containing proteins and fats, which play critical roles in chemical signaling, building cellular structures, transporting molecules, and producing energy.
2. Health Conditions Related to Genetic Changes
More than 20 mutations in the GALE gene have been identified in people with a form of galactosemia known as type III or galactose epimerase deficiency. The signs and symptoms of this condition begin shortly after birth and can vary from mild to severe. Most of the genetic changes alter a single protein building block (amino acid) in UDP-galactose-4-epimerase, which makes the enzyme unstable or impairs its usual function.
Some GALE gene mutations severely reduce or eliminate the activity of UDP-galactose-4-epimerase in all of the body's tissues. These genetic changes lead to a severe form of galactosemia type III described as the generalized form. A loss of enzyme activity prevents cells from processing galactose obtained from the diet. As a result, compounds associated with galactose processing can build up to toxic levels in the body. The accumulation of these substances damages tissues and organs, leading to serious complications such as clouding of the lens of the eye (cataract), intellectual disability, and damage to the liver, kidneys, and brain.
Other mutations in the GALE gene reduce the activity of UDP-galactose-4-epimerase in red blood cells only. These genetic changes underlie a much milder form of galactosemia type III described as the peripheral form. Affected individuals may not have any of the complications typically associated with galactosemia and often do not require treatment. Researchers are unclear why the effects of some GALE mutations are restricted to blood cells, while other mutations affect all of the body's tissues and cause severe health problems.
3. Other Names for This Gene
UDP - Uridyl diphosphate galactose-4-epimerase
UDP Galactose Epimerase
Uridine diphosphate galactose-4-epimerase
Uridine Diphosphate Glucose Epimerase
The entry is from https://medlineplus.gov/genetics/gene/gale
- Fridovich-Keil J, Bean L, He M, Schroer R. Epimerase Deficiency Galactosemia. 2011 Jan 25 [updated 2016 Jun 16]. In: Adam MP, Ardinger HH, Pagon RA, WallaceSE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle(WA): University of Washington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK51671/
- Pey AL, Padín-Gonzalez E, Mesa-Torres N, Timson DJ. The metastability of humanUDP-galactose 4'-epimerase (GALE) is increased by variants associated with typeIII galactosemia but decreased by substrate and cofactor binding. Arch BiochemBiophys. 2014 Nov 15;562:103-14. doi: 10.1016/j.abb.2014.07.030.
- Schulz JM, Watson AL, Sanders R, Ross KL, Thoden JB, Holden HM, Fridovich-KeilJL. Determinants of function and substrate specificity in human UDP-galactose4'-epimerase. J Biol Chem. 2004 Jul 30;279(31):32796-803.
- Timson DJ, Lindert S. Comparison of dynamics of wildtype and V94M humanUDP-galactose 4-epimerase-A computational perspective on severeepimerase-deficiency galactosemia. Gene. 2013 Sep 10;526(2):318-24. doi:10.1016/j.gene.2013.05.027.
- Timson DJ. Functional analysis of disease-causing mutations in humanUDP-galactose 4-epimerase. FEBS J. 2005 Dec;272(23):6170-7.
- Timson DJ. The structural and molecular biology of type III galactosemia.IUBMB Life. 2006 Feb;58(2):83-9. Review.