H6PD (Hexose-6-Phosphate Dehydrogenase)
Glucose-6-Phosphate Dehydrogenase-Like Enzyme in Endoplasmic Reticulum Redox Homeostasis
Gene Information Card
| Symbol | H6PD |
|---|---|
| Full Name | Hexose-6-Phosphate Dehydrogenase (Glucose 1-Dehydrogenase) |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.22 |
| NCBI Gene ID | 9563 ncbi.nlm.nih.gov/gene/9563 |
| Ensembl ID | ENSG00000149231 |
| UniProt ID | O95479 |
| OMIM ID | 138090 |
| HGNC ID | 4795 |
| Aliases | G6PDH, H6PDH, GDH, CORTRD2 |
Description
The H6PD gene encodes hexose-6-phosphate dehydrogenase, an endoplasmic reticulum (ER)-resident enzyme that catalyzes the first two steps of the pentose phosphate pathway within the ER lumen. It generates NADPH, which is essential for the activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), thereby regulating local glucocorticoid activation. Mutations in H6PD cause cortisone reductase deficiency type 2 (CORTRD2), a disorder of glucocorticoid metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cortisone reductase deficiency 2 (CORTRD2) | Loss-of-function mutations impair NADPH generation, reducing 11β-HSD1 reductase activity and causing glucocorticoid excess with androgen excess | OMIM #604931; ClinVar |
| Apparent cortisone reductase deficiency | Defective H6PD leads to inability to convert cortisone to cortisol, resulting in ACTH-driven adrenal hyperandrogenism | OMIM #138090; NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Adipose tissue | 8.3 | Medium |
| Kidney | 6.7 | Low |
| Adrenal gland | 5.1 | Low |
| Small intestine | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 10.2 | Hepatocyte line |
| HEK293 | 7.5 | Embryonic kidney |
| 3T3-L1 | 6.0 | Adipocyte precursor |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.325G>A (p.Gly109Arg) | Missense | Rare | Loss of enzymatic activity; associated with CORTRD2 |
| c.674C>T (p.Pro225Leu) | Missense | Rare | Reduced NADPH production; impaired 11β-HSD1 coupling |
| c.1039C>T (p.Arg347*) | Nonsense | Rare | Truncated protein; complete loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense and nonsense mutations reduce or abolish NADPH generation, leading to cortisone reductase deficiency.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported; H6PD deficiency is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • glucose-6-phosphate dehydrogenase activity (GO:0004345) | • aldehyde dehydrogenase [NAD(P)+] activity (GO:0004030) |
| • endoplasmic reticulum lumen (GO:0005783) | • pentose-phosphate shunt (GO:0006098) |
| • oxidation-reduction process (GO:0055114) |
Pathways
• Pentose phosphate pathway (endoplasmic reticulum variant)
• Glucocorticoid metabolism via 11β-HSD1
Protein Summary
Hexose-6-phosphate dehydrogenase is a 89 kDa ER luminal enzyme that catalyzes the conversion of glucose-6-phosphate to 6-phosphoglucono-δ-lactone, generating NADPH. This NADPH pool is specifically used by 11β-hydroxysteroid dehydrogenase type 1 to reduce cortisone to active cortisol. H6PD is structurally similar to cytosolic G6PD but contains an N-terminal signal peptide for ER targeting. Its activity is critical for tissue-specific glucocorticoid regulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| H6PD Knockout HEK293 Cell Line | EDJ-KQ5983 | Human | 9563 | Details Get a Quote |
| H6PD Knockout A-549 Cell Line | EDJ-KQ30907 | Human | 9563 | Details Get a Quote |
| H6PD Knockout HCT 116 Cell Line | EDJ-KQ30909 | Human | 9563 | Details Get a Quote |
| H6PD Knockout HeLa Cell Line | EDJ-KQ30910 | Human | 9563 | Details Get a Quote |
