Reviewed December 2013
What is the official name of the GPI gene?
The official name of this gene is “glucose-6-phosphate isomerase.”
GPI is the gene's official symbol. The GPI gene is also known by other names, listed below.
What is the normal function of the GPI gene?
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).
How are changes in the GPI gene related to health conditions?
- glucose phosphate isomerase deficiency - caused by mutations in the GPI gene
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.
Where is the GPI gene located?
Cytogenetic Location: 19q13.1
Molecular Location on chromosome 19: base pairs 34,359,592 to 34,402,413
The GPI gene is located on the long (q) arm of chromosome 19 at position 13.1.
More precisely, the GPI gene is located from base pair 34,359,592 to base pair 34,402,413 on chromosome 19.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about GPI?
You and your healthcare professional may find the following resources about GPI helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28%28glucose%20phosphate%20isomerase%5BTIAB%5D%29%20OR%20%28glucose-6-phosphate%20isomerase%5BTIAB%5D%29%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/172400)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_GPI.html)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=4458)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2821)
What other names do people use for the GPI gene or gene products?
- autocrine motility factor
- glucose phosphate isomerase
- hexose monophosphate isomerase
- hexosephosphate isomerase
- phosphoglucose isomerase
- phosphohexose isomerase
- sperm antigen 36
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding GPI?
hemolytic anemia ;
red cells ;
simple sugar ;
You may find definitions for these and many other terms in the Genetics Home Reference
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/8822952?dopt=Abstract)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/9446754?dopt=Abstract)
- 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/8931949?dopt=Abstract)
- OMIM: GLUCOSE-6-PHOSPHATE ISOMERASE (http://omim.org/entry/172400)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/8822954?dopt=Abstract)
- Kugler W, Breme K, Laspe P, Muirhead H, Davies C, Winkler H, Schröter 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. (http://www.ncbi.nlm.nih.gov/pubmed/9856489?dopt=Abstract)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/9362562?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2821)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/17041899?dopt=Abstract)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/22782259?dopt=Abstract)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/7989588?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.