GPI (Glucose-6-Phosphate Isomerase)
Key enzyme in glycolysis and gluconeogenesis, associated with hemolytic anemia and cancer metabolism
Gene Information Card
| Symbol | GPI |
|---|---|
| Full Name | Glucose-6-Phosphate Isomerase |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.11 |
| NCBI Gene ID | 2821 ncbi.nlm.nih.gov/gene/2821 |
| Ensembl ID | ENSG00000105220 |
| UniProt ID | P06744 |
| OMIM ID | 172400 |
| HGNC ID | 4458 |
| Aliases | AMF, GNPI, NLK, PGI, PHI, SA-36, HEL-S-49 |
Description
The GPI gene encodes glucose-6-phosphate isomerase, a cytosolic enzyme that catalyzes the reversible isomerization of glucose-6-phosphate to fructose-6-phosphate in glycolysis and gluconeogenesis. The protein also functions as a neurotrophic factor (neuroleukin) and as an autocrine motility factor (AMF) in cancer cells. Mutations in GPI cause GPI deficiency, a rare autosomal recessive disorder leading to hereditary nonspherocytic hemolytic anemia and neurological impairment.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| GPI Deficiency (Hereditary Nonspherocytic Hemolytic Anemia) | Loss-of-function mutations impair glycolysis, reducing ATP production in erythrocytes, leading to hemolysis. | ClinVar, OMIM |
| Neuropathy (associated with GPI deficiency) | Deficiency of neuroleukin activity affects motor neuron survival and function. | OMIM, PubMed |
| Cancer (various) | Overexpression of GPI/AMF promotes tumor cell motility, invasion, and metastasis. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 78.5 | High |
| Heart | 56.3 | High |
| Liver | 42.1 | High |
| Brain | 38.7 | High |
| Kidney | 35.2 | High |
| Lung | 28.9 | Medium |
| Pancreas | 25.6 | Medium |
| Spleen | 22.4 | Medium |
| Colon | 20.1 | Medium |
| Breast | 18.7 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 85.2 | Cervical cancer cell line |
| K-562 | 72.3 | Leukemia cell line |
| A549 | 68.1 | Lung cancer cell line |
| MCF7 | 55.4 | Breast cancer cell line |
| HEK293 | 49.7 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1040G>A (p.Arg347His) | Missense | ~5% of GPI deficiency cases | Reduces enzyme activity; causes hemolytic anemia |
| c.1028A>G (p.Asn343Ser) | Missense | ~3% | Impaired catalytic function; neurological symptoms |
| c.1459C>T (p.Arg487Cys) | Missense | ~2% | Decreased stability; mild anemia |
| c.166G>A (p.Gly56Arg) | Missense | <1% | Severe enzyme deficiency; hemolytic crisis |
Mutation functional classification
Loss of Function (LOF)
Most GPI mutations are loss-of-function, reducing or abolishing enzymatic activity, leading to hemolytic anemia and neurological deficits.
Gain of Function (GOF)
Not reported in germline; somatic overexpression in tumors may confer gain-of-function in cell motility.
Dominant Negative (DN)
Not described; GPI deficiency is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Glycolysis / Gluconeogenesis (KEGG: hsa00010)
• Pentose phosphate pathway (KEGG: hsa00030)
• Metabolic pathways (KEGG: hsa01100)
Protein Summary
Glucose-6-phosphate isomerase (GPI) is a 558-amino-acid homodimeric enzyme that interconverts glucose-6-phosphate and fructose-6-phosphate. It is ubiquitously expressed with highest levels in muscle and heart. Beyond its metabolic role, GPI acts as a neurotrophic factor (neuroleukin) supporting motor neuron survival, and as an autocrine motility factor (AMF) secreted by tumor cells to enhance migration and metastasis. Mutations cause GPI deficiency, a rare autosomal recessive disorder characterized by chronic hemolytic anemia and variable neurological involvement.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GPIHBP1 Knockout HEK293 Cell Line | EDJ-KQ13654 | Human | 338328 | Details Get a Quote |
| GPIHBP1 Knockout HeLa Cell Line | EDJ-KQ59607 | Human | 338328 | Details Get a Quote |
| GPIHBP1 Knockout A-549 Cell Line | EDJ-KQ68072 | Human | 338328 | Details Get a Quote |
| GPIHBP1 Knockout HCT 116 Cell Line | EDJ-KQ76449 | Human | 338328 | Details Get a Quote |
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