XDH (Xanthine Dehydrogenase) Gene
Key enzyme in purine metabolism and uric acid production
Gene Information Card
| Symbol | XDH |
|---|---|
| Full Name | Xanthine Dehydrogenase |
| Gene Type | Protein coding |
| Chromosomal Location | 2p23.1 |
| NCBI Gene ID | 7498 ncbi.nlm.nih.gov/gene/7498 |
| Ensembl ID | ENSG00000158125 |
| UniProt ID | P47989 |
| OMIM ID | 607633 |
| HGNC ID | 12805 |
| Aliases | XO, XOR, XDH1 |
Description
The XDH gene encodes xanthine dehydrogenase, a key enzyme in purine catabolism that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid. It belongs to the molybdenum cofactor hydroxylase family and can be converted to xanthine oxidase (XO) by reversible sulfhydryl oxidation or irreversible proteolytic cleavage. XDH plays a central role in uric acid production and is implicated in gout, xanthinuria, and oxidative stress.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Xanthinuria Type I | Loss-of-function mutations in XDH cause deficiency of xanthine dehydrogenase, leading to accumulation of xanthine and hypoxanthine and formation of xanthine stones. | ClinVar, OMIM #278300 |
| Hereditary Xanthinuria Type II | Combined deficiency of XDH and aldehyde oxidase due to defects in molybdenum cofactor sulfurase (MOCOS), but XDH mutations alone can mimic this phenotype. | OMIM #603592 |
| Gout | Increased XDH activity leads to elevated uric acid production, contributing to hyperuricemia and gout flares. | NCBI Gene, ClinVar |
| Xanthinuria with nephrolithiasis | XDH deficiency results in low uric acid and high xanthine levels, causing xanthine stones in the urinary tract. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 22.5 | High |
| Small intestine | 8.3 | Medium |
| Kidney | 6.1 | Medium |
| Breast | 4.2 | Low |
| Lung | 3.8 | Low |
| Heart | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 18.7 | Liver cancer cell line, high expression |
| Caco-2 | 9.5 | Colorectal adenocarcinoma, medium expression |
| HEK 293 | 2.1 | Embryonic kidney, low expression |
| A549 | 1.8 | Lung carcinoma, low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.682C>T (p.Arg228*) | Nonsense | Rare | Loss of function, associated with xanthinuria |
| c.2567G>A (p.Arg856His) | Missense | Rare | Reduced enzyme activity, linked to xanthinuria |
| c.1210C>T (p.Arg404Trp) | Missense | Rare | Loss of function, reported in xanthinuria patients |
| c.3448G>A (p.Gly1150Ser) | Missense | Rare | Decreased activity, possible modifier of gout risk |
Mutation functional classification
Loss of Function (LOF)
XDH loss-of-function mutations cause hereditary xanthinuria type I, characterized by low serum uric acid and xanthine stones.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported; increased expression or activity may contribute to hyperuricemia and gout.
Dominant Negative (DN)
No dominant-negative effects described for XDH; disease is typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Purine metabolism (KEGG: hsa00230)
• Metabolic pathways (KEGG: hsa01100)
• Caffeine metabolism (KEGG: hsa00232)
• Drug metabolism – other enzymes (KEGG: hsa00983)
Protein Summary
Xanthine dehydrogenase (XDH) is a homodimeric enzyme (150 kDa per subunit) that contains two 2Fe-2S clusters, one FAD cofactor, and one molybdenum cofactor (Moco). It catalyzes the hydroxylation of hypoxanthine to xanthine and xanthine to uric acid, with NAD+ as the electron acceptor in the dehydrogenase form. Under oxidative stress, XDH is converted to xanthine oxidase (XO), which uses oxygen as electron acceptor and produces superoxide radicals. XDH is primarily expressed in liver and intestine, and its activity is regulated by substrate availability and post-translational modifications.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| XDH Knockout HEK293 Cell Line | EDJ-KQ2277 | Human | 7498 | Details Get a Quote |
| XDH Knockout HeLa Cell Line | EDJ-KQ18264 | Human | 7498 | Details Get a Quote |
| XDH Knockout A-549 Cell Line | EDJ-KQ22623 | Human | 7498 | Details Get a Quote |
| XDH Knockout HCT 116 Cell Line | EDJ-KQ71717 | Human | 7498 | Details Get a Quote |
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