The HOGA1 gene provides instructions for making the 4-hydroxy-2-oxoglutarate aldolase (HOGA) enzyme. This enzyme is found in liver and kidney cells, specifically within structures called mitochondria, which are the energy-producing centers in cells. The HOGA enzyme is involved in breaking down a protein building block (amino acid) called hydroxyproline. Specifically, during the breakdown process, HOGA cuts (cleaves) a substance called 4-hydroxy-2-oxoglutarate to produce two smaller substances called pyruvate and glyoxylate. In mitochondria, pyruvate is likely involved in energy production, but the function of glyoxylate is unclear.
Health Conditions Related to Genetic Changes
At least 24 mutations in the HOGA1 gene have been found to cause primary hyperoxaluria type 3. This condition is caused by the overproduction of a substance called oxalate. Excess amounts of this substance lead to kidney and bladder stones, which begin in early childhood and often result in blood in the urine (hematuria) and urinary tract infections. A specific mutation that alters the way the gene's instructions are used to make the enzyme (written as 700+5G>T) is present in about half of affected individuals. As a result of HOGA1 gene mutations, the HOGA enzyme cannot break down 4-hydroxy-2-oxoglutarate, which leads to a buildup of this substance in the mitochondria of liver cells.
It is unclear how an accumulation of 4-hydroxy-2-oxoglutarate leads to an overproduction of oxalate in people with primary hyperoxaluria type 3. Some researchers think that the accumulation of 4-hydroxy-2-oxoglutarate interferes with the activity of other enzymes, which lead to the accumulation of substances that get converted into oxalate. Other researchers think that excess 4-hydroxy-2-oxoglutarate in mitochondria may leak out into liver cells. Enzymes within these cells would then convert 4-hydroxy-2-oxoglutarate to glyoxylate, and then convert glyoxylate into oxalate. In individuals with primary hyperoxaluria type 3, the oxalate is filtered through the kidneys and is either excreted in urine as a waste product or combines with calcium to form calcium oxalate, a hard compound that is the main component of kidney and bladder stones.More About This Health Condition
Other Names for This Gene
- dihydrodipicolinate synthase-like, mitochondrial
- dihydrodipicolinate synthetase homolog 2
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Cochat P, Rumsby G. Primary hyperoxaluria. N Engl J Med. 2013 Aug 15;369(7):649-58. doi: 10.1056/NEJMra1301564. No abstract available. Erratum In: N Engl J Med. 2013 Nov 28;369(22):2168. Citation on PubMed
- Hoppe B. The enzyme 4-hydroxy-2-oxoglutarate aldolase is deficient in primary hyperoxaluria type III. Nephrol Dial Transplant. 2012 Aug;27(8):3024-6. doi: 10.1093/ndt/gfs308. No abstract available. Citation on PubMed
- Milliner DS, Harris PC, Sas DJ, Lieske JC. Primary Hyperoxaluria Type 3. 2015 Sep 24 [updated 2023 Feb 9]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from http://www.ncbi.nlm.nih.gov/books/NBK316514/ Citation on PubMed
- Riedel TJ, Johnson LC, Knight J, Hantgan RR, Holmes RP, Lowther WT. Structural and biochemical studies of human 4-hydroxy-2-oxoglutarate aldolase: implications for hydroxyproline metabolism in primary hyperoxaluria. PLoS One. 2011;6(10):e26021. doi: 10.1371/journal.pone.0026021. Epub 2011 Oct 6. Citation on PubMed or Free article on PubMed Central
- Williams EL, Bockenhauer D, van't Hoff WG, Johri N, Laing C, Sinha MD, Unwin R, Viljoen A, Rumsby G. The enzyme 4-hydroxy-2-oxoglutarate aldolase is deficient in primary hyperoxaluria type 3. Nephrol Dial Transplant. 2012 Aug;27(8):3191-5. doi: 10.1093/ndt/gfs039. Epub 2012 Mar 5. Citation on PubMed