G6PD

Official Full Name

glucose-6-phosphate dehydrogenase

Organism

Homo sapiens

Gene ID

2539

Background

This gene encodes glucose-6-phosphate dehydrogenase. This protein is a cytosolic enzyme encoded by a housekeeping X-linked gene whose main function is to produce NADPH, a key electron donor in the defense against oxidizing agents and in reductive biosynthetic reactions. G6PD is remarkable for its genetic diversity. Many variants of G6PD, mostly produced from missense mutations, have been described with wide ranging levels of enzyme activity and associated clinical symptoms. G6PD deficiency may cause neonatal jaundice, acute hemolysis, or severe chronic non-spherocytic hemolytic anemia. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Synonyms

G6PD1; CNSHA1

Cat.No.	Product Name	Price
CSC-DC006002	Panoply™ Human G6PD Knockdown Stable Cell Line	Inquiry
CSC-SC006002	Panoply™ Human G6PD Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD06506Z	Human G6PD adenoviral particles	Inquiry
LV13246L	human G6PD (NM_001042351) lentivirus particles	Inquiry
LV13247L	human G6PD (NM_000402) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH072821	shRNA set against Human G6PD(NM_001042351.1)	Inquiry
SHH072839	shRNA set against Human G6PD(NM_000402.3)	Inquiry
SHH298273	shRNA set against Human G6PD (NM_000402.3)	Inquiry
SHH298277	shRNA set against Mouse G6PD (NM_019468.2)	Inquiry
SHH298281	shRNA set against Rat G6PD (NM_017006.2)	Inquiry

Cat.No.	Product Name	Price
CDCL184351	Human G6PD ORF clone(NM_000402.3)	Inquiry
CDCR344204	Human G6PD ORF Clone(NM_001042351.1)	Inquiry
CDCR378119	Rat G6pd ORF Clone(NM_017006.2)	Inquiry
CDFH007245	Human G6PD cDNA Clone(NM_000402.3)	Inquiry
CDFH007247	Human G6PD cDNA Clone(NM_001042351.1)	Inquiry
CDFR011076	Rat G6pd cDNA Clone(NM_017006.2)	Inquiry
MiUTR1H-03896	G6PD miRNA 3'UTR clone	Inquiry
MiUTR1H-03897	G6PD miRNA 3'UTR clone	Inquiry
MiUTR1R-02001	G6PD miRNA 3'UTR clone	Inquiry
CDCB195106	Rabbit G6PD ORF clone (XM_008250287.1)	Inquiry
CDCS405640	Human G6PD ORF Clone (BC000337)	Inquiry

Cat.No.	Product Name	Price
CC-545	G6PD Easy KO Kit	Inquiry

Detailed Information

Mammalian cells possess a few enzymes that are able to produce NADPH and, among them, glucose-6-phosphate dehydrogenase (G6PD) is considered the most important one. G6PD, the first rate-limited enzyme of the pentose-phosphate pathway (PPP), is encoded by a housekeeping gene, which is located on the Xq28 region and expressed in all cells.

G6PD deficiency

G6PD is a ubiquitously expressed enzyme which has a housekeeping role in all cells, and is particularly important to the integrity and functioning of red blood cells (RBCs). The G6PD gene has a number of mutant alleles which entail a decrease in enzyme activity, expressing the G6PD deficient phenotype. This trait is widespread in human populations in whom several of the underlying mutant alleles are present at variable polymorphic frequencies.

The advent of molecular diagnostics following the successful mapping of the G6PD gene’s 13 exons which span 18.5 kb, and the gene’s cloning and sequencing started to uncover the genetic basis to the enzyme’s great variability (Figure 1). This Mendelian X-linked gene is one of the most highly polymorphic of the human genome with at least 186 mutations having been described. That is to say, not all mutations are polymorphic and of public health significance, but many instead appear only sporadically within populations: nearly half are associated with the most severe clinical phenotypes and are very rare.

G6PD Figure 1. The diversity of the G6PD gene mutations and enzyme mutations.

There are two reasons for G6PD deficiency selectively affecting RBCs. First, most known mutations cause a decreased stability of the enzyme, and as these cells do not have the ability to synthesize proteins, the enzyme level decreases as cells age during their 120 days lifespan in circulation. Second, RBCs are exquisitely susceptible to oxidative stress from exogenous oxidizing agents in the blood and the oxygen radicals continuously generated as hemoglobin cycles between its deoxygenated and oxygenated forms. When G6PD activity is deficient, they have a diminished ability to withstand stress, and therefore risk destruction (hemolysis).

Fortunately, the large majority of G6PD deficient subjects have no clinical manifestations and the condition remains asymptomatic until they are exposed to a hemolytic trigger. For centuries, the most common known trigger of hemolysis has been fava beans, and favism remains a public health problem in areas where these are a common food item and G6PD deficiency is prevalent. Nevertheless, a haemolysing trigger of great contemporary public health significance is the antimalarial primaquine, a key drug for malaria control. Since its introduction, primaquine has emerged as a major drug trigger of hemolysis in G6PD deficient individuals, making this a paradigm of pharmacogenetics.

G6PD and cancer

To date, G6PD is thought to be involved in the regulation of cells proliferation and transformation. For instance, Kuo et al. transfected NIH 3T3 cells (a mouse fibroblast cell line) with human G6PD cDNA, then found that cells overexpressing G6PD showed the altered cell morphology, exhibited tumorigenic properties and gave rise to tumors in nude mice, which indicated that G6PD is a promoter of tumorigenesis. Moreover, B. Batetta et al. found that cells incubated with G6PD inhibitors and white blood cells from G6PD totally deficient subjects proliferated at a lower extent than cells from normal subjects. Li et al. demonstrated that silencing G6PD expression by siRNA decreased tumor cell proliferation and enhanced apoptosis. And more importantly, elevated G6PD activities have been found in various human cancers, including renal cell carcinoma, ovarian cancer, prostatic carcinoma, fibrosarcoma, breast cancer, endometrial carcinoma, bladder cancer, cervical carcinoma, and lung carcinoma.

In a recent study, researchers found that the levels of G6PD protein and mRNA were significantly higher in gastric cancer tissue compared with paired normal tissues, and the overexpression of G6PD proteins was significantly related to tumor size, invasion depth, lymph node metastasis, TNM stage and distant metastasis. All of these results show a strong correlation between G6PD and gastric cancer.

References:

Luzzatto L. G6PD deficiency and malaria selection. Heredity, 2012, 108(4):456.
Howes R E, et al. G6PD deficiency: global distribution, genetic variants and primaquine therapy. Advances in Parasitology, 2013, 81(81):133-201.
Sandrina N P, et al. G6PD protects from oxidative damage and improves healthspan in mice. Nature Communications, 2016, 7:10894.
Minucci A, et al. Glucose-6-phosphate dehydrogenase (G6PD) mutations database: review of the "old" and update of the new mutations. Blood Cells Molecules & Diseases, 2012, 48(3):154-165.
Wang J, et al. Overexpression of G6PD is associated with poor clinical outcome in gastric cancer. Tumor Biology, 2012, 33(1):95-101.

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