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Normal Function
The GPI gene provides instructions for making an enzyme called glucose phosphate isomerase (GPI). This enzyme has two distinct functions based on its structure. When two GPI molecules form a complex (a homodimer), the enzyme plays a role in a critical energy-producing process known as glycolysis, also called the glycolytic pathway. During glycolysis, the simple sugar glucose is broken down to produce energy. Specifically, GPI is involved in the second step of the glycolytic pathway; in this step, a molecule called glucose-6-phosphate is converted to another molecule called fructose-6-phosphate.
When GPI remains a single molecule (a monomer) it is involved in the development and maintenance of nerve cells (neurons). In this context, it is often known as neuroleukin (NLK).
The monomer is also produced by cancer cells and functions to promote spreading (metastasis) of the cancer; in this context it is called autocrine motility factor (AMF).
Health Conditions Related to Genetic Changes
Glucose phosphate isomerase deficiency
More than 30 GPI gene mutations have been identified in people with glucose phosphate isomerase (GPI) deficiency. GPI deficiency is an inherited disorder that affects red blood cells, which carry oxygen to the body's tissues. People with this disorder have a condition known as chronic hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, resulting in a shortage of red blood cells (anemia). Some affected individuals also have neurological problems, including intellectual disability and difficulty with coordinating movements (ataxia).
Most of the mutations that cause GPI deficiency replace single protein building blocks (amino acids) in the GPI enzyme. Some of these mutations may result in a less stable homodimer, impairing the activity of the enzyme in the glycolytic pathway. The resulting imbalance of molecules involved in the glycolytic pathway eventually impairs the ability of red cells to maintain their structure, leading to hemolysis.
Other GPI gene mutations may cause the monomer to break down more easily, thereby interfering with its function in nerve cells. In addition, the shortage of monomers hinders homodimer formation, which impairs the glycolytic pathway. These mutations have been identified in individuals with GPI deficiency who have both hemolytic anemia and neurological problems.
More About This Health ConditionOther Names for This Gene
- AMF
- autocrine motility factor
- G6PI_HUMAN
- glucose phosphate isomerase
- GNPI
- hexose monophosphate isomerase
- hexosephosphate isomerase
- neuroleukin
- NLK
- oxoisomerase
- PGI
- PHI
- phosphoglucose isomerase
- phosphohexomutase
- phosphohexose isomerase
- phosphosaccharomutase
- SA36
- sperm antigen 36
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Baronciani L, Zanella A, Bianchi P, Zappa M, Alfinito F, Iolascon A, Tannoia N, Beutler E, Sirchia G. Study of the molecular defects in glucose phosphate isomerase-deficient patients affected by chronic hemolytic anemia. Blood. 1996 Sep 15;88(6):2306-10. Citation on PubMed
- Beutler E, West C, Britton HA, Harris J, Forman L. Glucosephosphate isomerase (GPI) deficiency mutations associated with hereditary nonspherocytic hemolytic anemia (HNSHA). Blood Cells Mol Dis. 1997 Dec;23(3):402-9. doi: 10.1006/bcmd.1997.0157. Citation on PubMed
- Fujii H, Kanno H, Hirono A, Miwa S. Hematologically important mutations: molecular abnormalities of glucose phosphate isomerase deficiency. Blood Cells Mol Dis. 1996;22(2):96-7. doi: 10.1006/bcmd.1996.0014. No abstract available. Citation on PubMed
- Kanno H, Fujii H, Hirono A, Ishida Y, Ohga S, Fukumoto Y, Matsuzawa K, Ogawa S, Miwa S. Molecular analysis of glucose phosphate isomerase deficiency associated with hereditary hemolytic anemia. Blood. 1996 Sep 15;88(6):2321-5. Citation on PubMed
- Kugler W, Breme K, Laspe P, Muirhead H, Davies C, Winkler H, Schroter W, Lakomek M. Molecular basis of neurological dysfunction coupled with haemolytic anaemia in human glucose-6-phosphate isomerase (GPI) deficiency. Hum Genet. 1998 Oct;103(4):450-4. doi: 10.1007/s004390050849. Citation on PubMed
- Lakomek M, Winkler H. Erythrocyte pyruvate kinase- and glucose phosphate isomerase deficiency: perturbation of glycolysis by structural defects and functional alterations of defective enzymes and its relation to the clinical severity of chronic hemolytic anemia. Biophys Chem. 1997 Jun 30;66(2-3):269-84. doi: 10.1016/s0301-4622(97)00057-4. Citation on PubMed
- Repiso A, Oliva B, Vives-Corrons JL, Beutler E, Carreras J, Climent F. Red cell glucose phosphate isomerase (GPI): a molecular study of three novel mutations associated with hereditary nonspherocytic hemolytic anemia. Hum Mutat. 2006 Nov;27(11):1159. doi: 10.1002/humu.9466. Citation on PubMed
- Warang P, Kedar P, Ghosh K, Colah RB. Hereditary non-spherocytic hemolytic anemia and severe glucose phosphate isomerase deficiency in an Indian patient homozygous for the L487F mutation in the human GPI gene. Int J Hematol. 2012 Aug;96(2):263-7. doi: 10.1007/s12185-012-1122-x. Epub 2012 Jul 11. Citation on PubMed
- Xu W, Beutler E. The characterization of gene mutations for human glucose phosphate isomerase deficiency associated with chronic hemolytic anemia. J Clin Invest. 1994 Dec;94(6):2326-9. doi: 10.1172/JCI117597. Citation on PubMed or Free article on PubMed Central
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