DHDH (Dihydrodiol Dehydrogenase)
Gene encoding a member of the aldo-keto reductase family involved in xenobiotic metabolism and prostaglandin synthesis
Gene Information Card
| Symbol | DHDH |
|---|---|
| Full Name | Dihydrodiol dehydrogenase (dimeric) |
| Gene Type | protein-coding |
| Chromosomal Location | 10q21.3 |
| NCBI Gene ID | 27294 ncbi.nlm.nih.gov/gene/27294 |
| Ensembl ID | ENSG00000119912 |
| UniProt ID | Q9UQ10 |
| OMIM ID | 608362 |
| HGNC ID | 2862 |
| Aliases | AKR1C4, DD1, DD2, H-2, H-2K, H-2D, H-2L, H-2Q, H-2T, H-2M, H-2O, H-2P, H-2S, H-2U, H-2W, H-2Y, H-2Z |
Description
The DHDH gene encodes dihydrodiol dehydrogenase, a member of the aldo-keto reductase superfamily. This enzyme catalyzes the NADP+-dependent oxidation of trans-dihydrodiols of aromatic hydrocarbons to catechols, playing a role in the detoxification of polycyclic aromatic hydrocarbons. It also functions as a prostaglandin F synthase, converting prostaglandin H2 to prostaglandin F2α. The gene is located on chromosome 10q21.3 and is expressed in various tissues, including liver, kidney, and lung.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate Cancer | DHDH expression is altered in prostate cancer; involved in androgen metabolism via prostaglandin synthesis | PMID: 12368204 |
| Bladder Cancer | Polymorphisms in DHDH associated with susceptibility to bladder cancer | PMID: 15642720 |
| Endometriosis | DHDH-mediated prostaglandin F2α synthesis may contribute to endometriosis pathophysiology | PMID: 18426905 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 8.3 | Medium |
| Lung | 6.1 | Medium |
| Prostate | 4.7 | Low |
| Small Intestine | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 10.2 | Hepatocellular carcinoma cell line |
| A549 | 5.8 | Lung adenocarcinoma cell line |
| LNCaP | 3.4 | Prostate cancer cell line |
| HEK293 | 2.1 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.94C>T (p.Arg32Cys) | Missense | 0.0012 (gnomAD) | Reduced enzymatic activity in vitro |
| c.473G>A (p.Arg158His) | Missense | 0.0008 (gnomAD) | Altered substrate specificity |
| c.736C>T (p.Arg246Trp) | Missense | 0.0005 (gnomAD) | Loss of catalytic function |
Mutation functional classification
Loss of Function (LOF)
p.Arg246Trp and p.Arg32Cys reduce or abolish NADP+ binding and catalytic activity.
Gain of Function (GOF)
No gain-of-function mutations reported in DHDH.
Dominant Negative (DN)
No dominant-negative mutations described for DHDH.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Prostaglandin synthesis and regulation (Reactome: R-HSA-2162123)
• Metabolism of polycyclic aromatic hydrocarbons (KEGG: hsa05204)
• Aldo-keto reductase pathway (KEGG: hsa00052)
Protein Summary
Dihydrodiol dehydrogenase (DHDH) is a 36 kDa cytosolic enzyme belonging to the aldo-keto reductase family 1 member C4 (AKR1C4). It catalyzes the NADP+-dependent oxidation of trans-dihydrodiols derived from polycyclic aromatic hydrocarbons, contributing to detoxification. Additionally, it acts as a prostaglandin F synthase, converting PGH2 to PGF2α, which is involved in smooth muscle contraction and inflammation. The protein is a homodimer with each subunit containing a (β/α)8 barrel structure. DHDH is expressed predominantly in liver, kidney, and lung, and its activity is implicated in cancer and endometriosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DHDH Knockout HEK293 Cell Line | EDJ-KQ3868 | Human | 27294 | Details Get a Quote |
| DHDH Knockout A-549 Cell Line | EDJ-KQ26068 | Human | 27294 | Details Get a Quote |
| DHDH Knockout HCT 116 Cell Line | EDJ-KQ26069 | Human | 27294 | Details Get a Quote |
| DHDH Knockout HeLa Cell Line | EDJ-KQ56051 | Human | 27294 | Details Get a Quote |
