DUOXA1

Chr 15

dual oxidase maturation factor 1

Also known as: NIP, NUMBIP, mol

NCBI Gene: 90527 ENSG00000140254 UniProt: Q1HG43

Dual oxidases DUOX1 and DUOX2 are NADPH oxidases which are involved in hydrogen peroxide production necessary for thyroid hormonogenesis. They form a heterodimer with specific maturation factors DUOXA1 and DUOXA2, respectively, which is essential for the maturation and function of the DUOX enzyme complexes. This gene encodes the DUOX1 activator or maturation factor DUOXA1. Rat studies identified a bidirectional promoter which controls the transcription of the DUOX1 and DUOXA1 genes. This protein is cotransported to the cell surface when coexpressed with DUOX1 and is retained in the endoplasmic reticulum when expressed without DUOX1 protein. The expression of this gene or the DUOX1 gene is not suppressed by thyroglobulin (Tg), a macromolecular precursor in thyroid hormone synthesis, while the expression of the DUOX2 and DUOXA2 are significantly suppressed by the Tg. This protein is also a p53-regulated neurogenic factor involved in p53 dependent neuronal differentiation. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2013]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (2)

gnomad: Error: gnomAD API error: 400

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in DUOXA1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

642 rare PASS variants

Rare truncating (LoF)

1 in 2,400

76 rare PASS variants

Rare synonymous (reference)

1 in 300

254 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DUOXA1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 2,800
South Asian	~43k	1 in 92	1 in 2,100
Remaining (unassigned)	~30k	1 in 85	1 in 3,000
European (Finnish)	~27k	1 in 250	1 in 3,800
Admixed American	~22k	1 in 78	1 in 2,800
African / African American	~21k	1 in 89	1 in 480
East Asian	~20k	1 in 92	1 in 1,100
Ashkenazi Jewish	~13k	1 in 360	1 in 2,200
Middle Eastern	~2,884	1 in 72	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓