HGD Gene - Homogentisate 1,2-Dioxygenase
Genetic and Functional Insights into Alkaptonuria and Tyrosine Metabolism
Gene Information Card
| Symbol | HGD |
|---|---|
| Full Name | homogentisate 1,2-dioxygenase |
| Gene Type | protein-coding |
| Chromosomal Location | 3q13.33 |
| NCBI Gene ID | 3081 ncbi.nlm.nih.gov/gene/3081 |
| Ensembl ID | ENSG00000113924 |
| UniProt ID | Q93099 |
| OMIM ID | 607474 |
| HGNC ID | 4890 |
| Aliases | AKU, HGO |
Description
The HGD gene encodes homogentisate 1,2-dioxygenase, an enzyme involved in the catabolism of tyrosine. It catalyzes the conversion of homogentisate to maleylacetoacetate. Loss-of-function mutations in HGD cause alkaptonuria (AKU), a rare autosomal recessive disorder characterized by accumulation of homogentisic acid, leading to ochronosis and joint degeneration.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alkaptonuria | Loss-of-function mutations in HGD impair homogentisate 1,2-dioxygenase activity, causing accumulation of homogentisic acid and its oxidation products, leading to ochronosis and joint damage. | OMIM #203500; multiple case-control and family studies confirm biallelic HGD mutations as causative. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Small intestine | 5.1 | Low |
| Prostate | 3.2 | Low |
| Lung | 1.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line; high expression |
| HEK 293 | 7.8 | Embryonic kidney cells; moderate expression |
| A549 | 2.1 | Lung carcinoma; low expression |
| K-562 | 0.5 | Leukemia; not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.481G>A (p.Gly161Arg) | Missense | Common in European AKU patients | Loss of function |
| c.174C>A (p.Phe58Leu) | Missense | Found in multiple AKU families | Loss of function |
| c.688C>T (p.Arg230Ter) | Nonsense | Reported in AKU | Loss of function |
| c.808G>A (p.Gly270Arg) | Missense | Observed in AKU | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most HGD mutations cause complete or partial loss of homogentisate 1,2-dioxygenase enzymatic activity, leading to alkaptonuria.
Gain of Function (GOF)
No gain-of-function mutations reported for HGD.
Dominant Negative (DN)
No dominant-negative effects described; alkaptonuria is recessive.
View complete mutation data：
Gene Ontology (GO)
| • homogentisate 1 | • 2-dioxygenase activity |
| • iron ion binding | • tyrosine catabolic process |
| • oxidation-reduction process | • cytoplasm |
Pathways
• Tyrosine metabolism (KEGG: hsa00350)
• Degradation of aromatic compounds
Protein Summary
Homogentisate 1,2-dioxygenase (HGD) is a 445-amino acid enzyme that belongs to the dioxygenase family. It requires ferrous iron as a cofactor and catalyzes the oxidative cleavage of the aromatic ring of homogentisate. The protein is primarily expressed in the liver and kidney. Defects in HGD cause alkaptonuria, a rare metabolic disorder.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ARHGDIA Knockout HEK293 Cell Line | EDJ-KQ3796 | Human | 396 | Details Get a Quote |
| PHGDH Knockout HEK293 Cell Line | EDJ-KQ3927 | Human | 26227 | Details Get a Quote |
| ARHGDIB Knockout HEK293 Cell Line | EDJ-KQ4087 | Human | 397 | Details Get a Quote |
| ARHGDIG Knockout HEK293 Cell Line | EDJ-KQ4088 | Human | 398 | Details Get a Quote |
| HGD Knockout HEK293 Cell Line | EDJ-KQ4862 | Human | 3081 | Details Get a Quote |
| D2HGDH Knockout HEK293 Cell Line | EDJ-KQ13090 | Human | 728294 | Details Get a Quote |
| L2HGDH Knockout HEK293 Cell Line | EDJ-KQ14021 | Human | 79944 | Details Get a Quote |
| PHGDH Knockout A-549 Cell Line | EDJ-KQ26164 | Human | 26227 | Details Get a Quote |
| PHGDH Knockout HCT 116 Cell Line | EDJ-KQ26165 | Human | 26227 | Details Get a Quote |
| L2HGDH Knockout A-549 Cell Line | EDJ-KQ43926 | Human | 79944 | Details Get a Quote |
| L2HGDH Knockout HCT 116 Cell Line | EDJ-KQ43927 | Human | 79944 | Details Get a Quote |
| L2HGDH Knockout HeLa Cell Line | EDJ-KQ43928 | Human | 79944 | Details Get a Quote |
| ARHGDIA Knockout HeLa Cell Line | EDJ-KQ24551 | Human | 396 | Details Get a Quote |
| PHGDH Knockout HeLa Cell Line | EDJ-KQ24819 | Human | 26227 | Details Get a Quote |
| ARHGDIA Knockout A-549 Cell Line | EDJ-KQ25907 | Human | 396 | Details Get a Quote |
Displaying Records 1 To 15 Of 29 Records
