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TAT
tyrosine aminotransferase
TAT is located on the long (q) arm of chromosome 16, at band 16q22.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The TAT gene encodes tyrosine aminotransferase, a hepatic enzyme that catalyses the first step in the degradation of tyrosine. This amino acid is a common constituent of dietary protein and must be efficiently metabolised to prevent toxic accumulation. The enzyme converts tyrosine into 4-hydroxyphenylpyruvate, which then undergoes further breakdown through a cascade of enzymatic reactions.
Pathogenic changes in TAT follow an autosomal recessive inheritance pattern, meaning that two altered copies (one inherited from each parent) are required for clinical manifestations to occur. When both copies are non-functional, tyrosine levels rise in the blood and tissues, potentially causing damage to the cornea, skin, and central nervous system. Carrier screening can identify individuals who carry one altered copy and may be at risk of having affected children.
What the gene does
Tyrosine aminotransferase operates primarily in liver cells, where it initiates the catabolism of tyrosine by transferring an amino group to 2-oxoglutarate (also known as alpha-ketoglutarate). This transamination reaction produces 4-hydroxyphenylpyruvate and glutamate. The 4-hydroxyphenylpyruvate product then enters subsequent enzymatic steps that ultimately yield molecules used for energy production or excreted by the kidneys.
The enzyme's activity is tightly regulated to match the body's tyrosine load, which varies with dietary protein intake. Proper function of tyrosine aminotransferase prevents the buildup of tyrosine and related metabolites, which can crystallise in tissues and cause cellular injury. By maintaining balanced tyrosine levels, the enzyme supports normal growth, vision, and skin integrity. The protein functions as part of the broader network of amino acid metabolism, ensuring that nitrogen-containing building blocks are efficiently recycled or eliminated.
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Chromosome location
The TAT gene is situated at chromosomal band 16q22.2 on the long arm of chromosome 16. This genomic region contains the regulatory sequences and coding information necessary to produce the 454-amino-acid tyrosine aminotransferase protein. Structural details regarding exon count and transcript variants are documented in genomic databases maintained by international consortia.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein. The 454-amino-acid tyrosine aminotransferase polypeptide adopts a fold that supports its enzymatic activity, including a catalytic site capable of binding tyrosine and 2-oxoglutarate substrates. Structural studies of related aminotransferases suggest that the active site geometry is critical for efficient transamination, though specific domain annotations for human TAT remain limited in current reference databases.
Key variants
At least 22 pathogenic variants in TAT have been identified, with the majority involving single-nucleotide changes that alter individual DNA building blocks. Research suggests these alterations produce an enzyme with reduced or absent catalytic activity. Some variants lead to complete deletion of portions of the gene, eliminating functional protein production. The variant landscape reflects the diverse ways in which genetic changes can disrupt tyrosine aminotransferase function, all resulting in impaired tyrosine breakdown when present in both gene copies.
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.169C>T | p.Arg57Ter | Pathogenic | ★★☆☆ | Tyrosinemia type II |
c.177dup | p.Val60fs | Pathogenic | ★★☆☆ | Tyrosinemia type II |
c.226dup | p.Leu76fs | Pathogenic/Likely pathogenic | ★★☆☆ | Tyrosinemia type II |
c.308_309delinsAA | p.Ser103Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Tyrosinemia type II |
c.355C>T | p.Arg119Trp | Pathogenic/Likely pathogenic | ★★☆☆ | Tyrosinemia type II |
c.307_308delinsCCT | p.Ser103fs | Pathogenic | ★☆☆☆ | Tyrosinemia type II |
c.308C>A | p.Ser103Ter | Pathogenic | ★☆☆☆ | Tyrosinemia type II |
c.351del | p.Ser118fs | Pathogenic | ★☆☆☆ | Tyrosinemia type II |
c.355del | p.Arg119fs | Pathogenic | ★☆☆☆ | Tyrosinemia type II |
c.364dup | p.Ile122fs | Pathogenic | ★☆☆☆ | Tyrosinemia type II |
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 TAT cause tyrosinaemia type II (Richner-Hanhart), an autosomal recessive disorder characterised by elevated tyrosine levels in the blood and tissues. Clinical features often include painful corneal erosions and plaques, which can develop in early childhood and impair vision. Skin lesions, particularly on the palms and soles, are also common. Some individuals experience intellectual disability or other neurological effects, though the phenotype varies. Early diagnosis and dietary management to reduce tyrosine intake can help mitigate symptoms and prevent complications.
- Tyrosinaemia type II (Richner-Hanhart) Dedicated page coming soon
Inheritance pattern
Conditions caused by pathogenic TAT 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 TAT gene appears on multiple NHS Genomic Medicine Service gene panels with green (high evidence) status. These include the DDG2P developmental disorders panel, the Ichthyosis and erythrokeratoderma panel (R165), the Intellectual disability panel (R29), and the Likely inborn error of metabolism panel (R98). It is also listed on panels for palmoplantar keratoderma and erythrokeratodermas, as well as undiagnosed metabolic disorders. Green classification indicates strong evidence linking TAT variants to the specified conditions, supporting its use in NHS diagnostic pathways for patients with relevant clinical presentations.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does it mean to be a carrier of a TAT variant?
Carriers have one working copy and one altered copy of the TAT gene. They typically do not show symptoms of tyrosinaemia type II because the single functional copy produces enough enzyme for normal tyrosine metabolism. However, if both parents are carriers, each child has a 25% chance of inheriting two altered copies and developing the condition.
How is tyrosinaemia type II managed?
Management typically involves a diet low in tyrosine and phenylalanine (which converts to tyrosine) to reduce the accumulation of tyrosine in the blood and tissues. Early dietary intervention can help prevent or reduce corneal and skin lesions. Regular monitoring by metabolic specialists and ophthalmologists is important to adjust treatment and assess for complications.
Is TAT testing available on the NHS?
Testing for TAT variants is available through NHS laboratories when clinically indicated, particularly for individuals with symptoms suggestive of tyrosinaemia type II or family history of the condition. The gene's inclusion on multiple NHS gene panels reflects its established role in metabolic and developmental disorders, supporting access to diagnostic sequencing through appropriate referral pathways.
References
- Bouyacoub Y, Zribi H, Azzouz H. Novel and recurrent mutations in the TAT gene in Tunisian families affected with Richner-Hanhart syndrome. Gene. 2013. PMID: 23954227
- Mehere P, Han Q, Lemkul JA. Tyrosine aminotransferase: biochemical and structural properties and molecular dynamics simulations. Protein & cell. 2010. PMID: 21153519
- Sivaraman S, Kirsch JF. The narrow substrate specificity of human tyrosine aminotransferase--the enzyme deficient in tyrosinemia type II. The FEBS journal. 2006. PMID: 16640556