On this page
OAT
ornithine aminotransferase
The OAT gene provides instructions for the ornithine aminotransferase enzyme, which plays a vital role in the breakdown of ornithine and the balance of amino acids within the body. The OAT gene encodes ornithine aminotransferase, an enzyme found in cellular mitochondria that is essential for processing ornithine.
OAT is located on the long (q) arm of chromosome 10, at band 10q26.13. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 10 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The OAT gene, or ornithine aminotransferase gene, contains the genetic blueprint for creating the ornithine aminotransferase enzyme. This enzyme is primarily active within the mitochondria, the energy-producing centres of cells, where it is involved in breaking down ornithine.
Ornithine metabolism is important for several bodily functions, including the urea cycle, which eliminates excess nitrogen, and maintaining the balance of various amino acids. Disruptions to the OAT gene can impact these metabolic pathways, leading to specific health conditions.
What the gene does
The ornithine aminotransferase (OAT) enzyme facilitates the conversion of ornithine into pyrroline-5-carboxylate (P5C) within the mitochondria. This conversion is a key step in amino acid metabolism. Ornithine itself is involved in the urea cycle, a process that removes ammonia, a by-product of protein breakdown, from the body.
Beyond its role in nitrogen removal, the OAT enzyme's activity helps maintain appropriate levels of protein building blocks. The P5C produced can be further converted into the amino acids proline and glutamate. Glutamate acts as an important neurotransmitter in the brain, stimulating nerve cells and contributing to normal brain function. It is also a precursor for gamma-amino butyric acid (GABA), another neurotransmitter that helps regulate brain activity.
Video: Genetics 101
Chromosome location
The OAT gene is located on chromosome 10, specifically at position 10q26.13. This chromosomal address indicates its precise position on the long arm (q) of chromosome 10, within band 26.13.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variations within the OAT gene can impact the production or function of the ornithine aminotransferase enzyme. These variations, known as pathogenic variants, can lead to a reduced amount of functional enzyme or an enzyme with impaired activity. The specific effect of a variant often depends on its nature and location within the gene.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1112dup | p.Arg372fs | Pathogenic/Likely pathogenic | ★★☆☆ | OAT-related disorder |
c.1163G>A | p.Trp388Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Ornithine aminotransferase deficiency |
c.152G>A | p.Gly51Asp | Pathogenic/Likely pathogenic | ★★☆☆ | Hyperornithinemia |
c.182_189del | p.Ala61fs | Pathogenic/Likely pathogenic | ★★☆☆ | Ornithine aminotransferase deficiency |
c.198del | p.Gly67fs | Pathogenic/Likely pathogenic | ★★☆☆ | Ornithine aminotransferase deficiency |
c.498C>G | p.Tyr166Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Ornithine aminotransferase deficiency |
c.515_516del | p.Phe172fs | Pathogenic/Likely pathogenic | ★★☆☆ | Ornithine aminotransferase deficiency |
c.776del | p.Leu259fs | Pathogenic/Likely pathogenic | ★★☆☆ | Ornithine aminotransferase deficiency |
c.796C>T | p.Gln266Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Ornithine aminotransferase deficiency |
c.896dup | p.Tyr299Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Ornithine aminotransferase deficiency |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the OAT gene are linked to several inherited conditions, primarily gyrate atrophy. Gyrate atrophy is a progressive eye disorder characterised by vision loss that worsens over time, ultimately affecting the retina and choroid. This condition is inherited in an autosomal recessive pattern.
Inheritance pattern
Conditions caused by pathogenic OAT variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The OAT gene is included in several expert-curated panels within the UK National Health Service (NHS) Genomic Medicine Service, as listed in PanelApp. It is part of panels for Hyperammonaemia, Likely inborn error of metabolism (R98), Retinal disorders (R32), and Undiagnosed metabolic disorders, all of which are rated 'green', indicating they are considered of high diagnostic utility.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the OAT gene?
The OAT gene provides instructions for the ornithine aminotransferase enzyme, which is crucial for breaking down ornithine in the mitochondria. This enzyme helps in the urea cycle to remove excess nitrogen and contributes to the balance of amino acids like proline and glutamate.
What condition is most commonly associated with OAT gene variants?
Pathogenic variants in the OAT gene are most commonly associated with gyrate atrophy. This is an inherited eye disorder characterised by progressive vision loss due to damage to the retina and choroid.
How is gyrate atrophy inherited?
Gyrate atrophy, caused by pathogenic variants in the OAT gene, follows an autosomal recessive inheritance pattern. This means an individual must inherit two copies of the altered gene, one from each parent, to develop the condition.
References
- Ohkubo Y, Ueta A, Ito T. Vitamin B6-responsive ornithine aminotransferase deficiency with a novel mutation G237D. The Tohoku journal of experimental medicine. 2005. PMID: 15750329
- Peltola KE, Näntö-Salonen K, Heinonen OJ. Ophthalmologic heterogeneity in subjects with gyrate atrophy of choroid and retina harboring the L402P mutation of ornithine aminotransferase. Ophthalmology. 2001. PMID: 11297489
- Mashima YG, Weleber RG, Kennaway NG. Genotype-phenotype correlation of a pyridoxine-responsive form of gyrate atrophy. Ophthalmic genetics. 1999. PMID: 10617919
- Mitchell GA, Brody LC, Looney J. An initiator codon mutation in ornithine-delta-aminotransferase causing gyrate atrophy of the choroid and retina. The Journal of clinical investigation. 1988. PMID: 3339136