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DUOXA2
dual oxidase maturation factor 2
The *DUOXA2* gene provides instructions for making a protein crucial for the proper maturation and function of dual oxidases, which are essential enzymes in thyroid hormone synthesis. The *DUOXA2* gene is vital for the production of thyroid hormones, playing a key role in the maturation of DUOX proteins.
DUOXA2 is located on the long (q) arm of chromosome 15, at band 15q21.1. Arm ratio per GRCh38 - banding schematic.
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Clinical tests that include this
Overview
The *DUOXA2* gene, also known as dual oxidase maturation factor 2, encodes a protein that is fundamental for the correct folding and activation of dual oxidase (DUOX) enzymes. These DUOX enzymes are responsible for generating hydrogen peroxide, a crucial component needed for the synthesis of thyroid hormones in the thyroid gland.
Disruptions in *DUOXA2* function can therefore impede the normal production of thyroid hormones, impacting various bodily processes. The gene's role highlights its importance in maintaining endocrine system health, particularly thyroid function.
What the gene does
The protein produced from the *DUOXA2* gene acts as a maturation factor for dual oxidase enzymes, specifically DUOX1 and DUOX2. These DUOX enzymes are located at the apical membrane of thyroid follicular cells, where they generate hydrogen peroxide (H2O2).
H2O2 is an essential substrate for thyroid peroxidase (TPO), another enzyme involved in organification and coupling reactions necessary for thyroid hormone synthesis. The DUOXA2 protein assists in the correct folding, trafficking, and activation of DUOX enzymes, ensuring they can efficiently produce H2O2. Without functional DUOXA2, DUOX enzymes cannot properly mature or become active, leading to insufficient H2O2 production and consequently, impaired thyroid hormone synthesis.
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Chromosome location
The *DUOXA2* gene is found on chromosome 15, specifically at position 15q21.1. This location indicates its position on the long (q) arm of chromosome 15. The accurate positioning of the gene on the chromosome is important for genetic mapping and understanding potential chromosomal rearrangements.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variations within the *DUOXA2* gene can alter the function or production of the DUOXA2 protein. These changes may include single nucleotide variants (SNVs), small insertions or deletions, or larger structural rearrangements. Depending on their nature and location, variants can lead to a range of effects on protein function, from mild reductions in activity to complete loss of function. These genetic differences form the basis for various inherited conditions associated with *DUOXA2*.
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.413dup | p.Tyr138Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Familial thyroid dyshormonogenesis |
c.738C>G | p.Tyr246Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Familial thyroid dyshormonogenesis |
c.95dup | p.Leu32fs | Pathogenic/Likely pathogenic | ★★☆☆ | Thyroglobulin synthesis defect |
c.10_11dup | p.Trp4fs | Pathogenic | ★☆☆☆ | not provided |
c.136del | p.Arg46fs | Pathogenic | ★☆☆☆ | Thyroglobulin synthesis defect |
c.298del | p.Arg100fs | Pathogenic | ★☆☆☆ | Thyroglobulin synthesis defect |
c.37C>T | p.Gln13Ter | Pathogenic | ★☆☆☆ | Thyroglobulin synthesis defect |
c.414C>G | p.Tyr138Ter | Pathogenic | ★☆☆☆ | Thyroglobulin synthesis defect |
c.573G>A | p.Trp191Ter | Pathogenic | ★☆☆☆ | Thyroglobulin synthesis defect |
c.604G>A | p.Ala202Thr | Pathogenic | - | Thyroglobulin synthesis defect |
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
Variants in the *DUOXA2* gene are primarily associated with conditions affecting thyroid hormone production. The most well-recognised condition linked to *DUOXA2* variants is congenital hypothyroidism. This condition involves insufficient thyroid hormone production from birth, which can have significant developmental impacts if not treated early. The severity of the condition can vary depending on the specific variant and its effect on protein function.
No disease links recorded for this gene in our reference set.
UK clinical status
The *DUOXA2* gene is recognised within the UK National Health Service (NHS) Genomic Medicine Service. It is included on the green R145 panel for congenital hypothyroidism, indicating that variants in this gene are considered to have a strong association with the condition and are routinely screened for in relevant clinical contexts.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the DUOXA2 gene?
The *DUOXA2* gene provides instructions for making a protein that helps dual oxidase (DUOX) enzymes mature and function correctly. These DUOX enzymes are essential for producing hydrogen peroxide, which is needed to create thyroid hormones in the thyroid gland.
How do variants in DUOXA2 affect health?
Variants in *DUOXA2* can impair the maturation and function of DUOX enzymes, leading to insufficient production of hydrogen peroxide. This results in reduced or absent thyroid hormone synthesis, primarily causing congenital hypothyroidism.
Is DUOXA2 testing available in the NHS?
Yes, the *DUOXA2* gene is part of the NHS Genomic Medicine Service. It is included on the R145 panel for congenital hypothyroidism, meaning genetic testing for variants in this gene is part of routine clinical assessment for this condition.