HOGA1 Gene - 4-Hydroxy-2-Oxoglutarate Aldolase 1
Genetic and Functional Insights into HOGA1: Role in Primary Hyperoxaluria Type 3 and Metabolic Pathways
Gene Information Card
| Symbol | HOGA1 |
|---|---|
| Full Name | 4-hydroxy-2-oxoglutarate aldolase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 10q24.2 |
| NCBI Gene ID | 112817 ncbi.nlm.nih.gov/gene/112817 |
| Ensembl ID | ENSG00000120063 |
| UniProt ID | Q86XE5 |
| OMIM ID | 613597 |
| HGNC ID | 25155 |
| Aliases | DHDPS2, NPL2, PRO1836 |
Description
The HOGA1 gene encodes 4-hydroxy-2-oxoglutarate aldolase 1, a mitochondrial enzyme involved in the catabolism of hydroxyproline. It catalyzes the cleavage of 4-hydroxy-2-oxoglutarate into glyoxylate and pyruvate. Mutations in HOGA1 cause primary hyperoxaluria type 3 (PH3), an autosomal recessive disorder characterized by calcium oxalate kidney stones and nephrocalcinosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary hyperoxaluria type 3 (PH3) | Loss-of-function mutations in HOGA1 impair the cleavage of 4-hydroxy-2-oxoglutarate, leading to accumulation of glyoxylate and subsequent oxalate overproduction, resulting in calcium oxalate stone formation. | ClinVar, OMIM #613597 |
| Nephrolithiasis (calcium oxalate kidney stones) | HOGA1 deficiency disrupts hydroxyproline metabolism, increasing oxalate synthesis and urinary oxalate excretion. | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Small intestine | 4.1 | Low |
| Pancreas | 3.0 | Low |
| Spleen | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 10.2 | Hepatocellular carcinoma cell line |
| HEK293 (embryonic kidney) | 6.5 | Embryonic kidney cells |
| A549 (lung) | 2.1 | Lung carcinoma cell line |
| K562 (bone marrow) | 0.8 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.700C>T (p.Arg234Cys) | Missense | Rare | Loss of enzyme activity; associated with PH3 |
| c.944_946del (p.Phe315del) | Deletion | Rare | In-frame deletion; reduced aldolase activity |
| c.415G>A (p.Gly139Arg) | Missense | Rare | Impaired catalytic function; PH3 |
| c.862C>T (p.Arg288Trp) | Missense | Rare | Loss of function; PH3 |
Mutation functional classification
Loss of Function (LOF)
Most HOGA1 mutations are loss-of-function, reducing or abolishing aldolase activity, leading to glyoxylate accumulation and oxalate overproduction in primary hyperoxaluria type 3.
Gain of Function (GOF)
No gain-of-function mutations have been reported for HOGA1.
Dominant Negative (DN)
No dominant-negative effects have been described; PH3 is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • catalytic activity (GO:0003824) | • mitochondrion (GO:0005739) |
| • 4-hydroxy-2-oxoglutarate aldolase activity (GO:0008700) | • carnitine metabolic process (GO:0009437) |
| • 4-hydroxyproline catabolic process (GO:0019470) | • identical protein binding (GO:0042802) |
Pathways
• Hydroxyproline degradation (Reactome: R-HSA-389661)
• Metabolism of amino acids and derivatives (Reactome: R-HSA-71291)
• Glyoxylate metabolism and glycine degradation (Reactome: R-HSA-389662)
Protein Summary
HOGA1 is a mitochondrial homodimeric enzyme (UniProt Q86XE5) that catalyzes the reversible aldol cleavage of 4-hydroxy-2-oxoglutarate to glyoxylate and pyruvate. It plays a key role in hydroxyproline catabolism. The protein is 327 amino acids long and contains a DHDPS-like domain. Loss of function leads to primary hyperoxaluria type 3.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HOGA1 Knockout HEK293 Cell Line | EDJ-KQ7397 | Human | 112817 | Details Get a Quote |
| HOGA1 Knockout HCT 116 Cell Line | EDJ-KQ31183 | Human | 112817 | Details Get a Quote |
| HOGA1 Knockout A-549 Cell Line | EDJ-KQ32550 | Human | 112817 | Details Get a Quote |
| HOGA1 Knockout HeLa Cell Line | EDJ-KQ57899 | Human | 112817 | Details Get a Quote |
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