DUOXA2

Chr 15

dual oxidase maturation factor 2

Also known as: SIMNIPHOM, TDH5

NCBI Gene: 405753 ENSG00000140274 UniProt: Q1HG44

This gene encodes an endoplasmic reticulum protein that is necessary for proper cellular localization and maturation of functional dual oxidase 2. Mutations in this gene have been associated with thyroid dyshormonogenesis 5.[provided by RefSeq, Feb 2010]

GeneReviews Research

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtThyroid dyshormonogenesis 5

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.92

LOEUF

Mechanism· predicted

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GeneReview available — DUOXA2

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.92LOEUF

pLI 0.000

Z-score -1.69

OE 1.52 (1.04–1.92)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.05Z-score

OE missense 1.22 (1.09–1.36)

228 obs / 187.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.52 (1.04–1.92)

0≤0.351.4

Missense OE?1.22 (1.09–1.36)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 19 / 12.5Missense obs/exp: 228 / 187.6Syn Z: 0.29

Background carrier burden — how many people carry a rare variant somewhere in DUOXA2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

515 rare PASS variants

Rare truncating (LoF)

1 in 550

79 rare PASS variants

Rare synonymous (reference)

1 in 540

199 rare PASS variants

Rare missense and truncating variants are carried at similar rates in DUOXA2; this gene does not show strong loss-of-function constraint by this measure. 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 190	1 in 1,800
South Asian	~43k	1 in 110	1 in 1,100
Remaining (unassigned)	~30k	1 in 92	1 in 270
European (Finnish)	~27k	1 in 660	1 in 2,700
Admixed American	~22k	1 in 220	1 in 660
African / African American	~21k	1 in 150	1 in 680
East Asian	~20k	1 in 110	≈ 1 in 5,000
Ashkenazi Jewish	~13k	≈ 1 in 4,300	none seen
Middle Eastern	~2,884	1 in 140	≈ 1 in 1,400

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 ↓