DUOXA2 (dual oxidase maturation factor 2)

Gene

• Entrez ID: 405753
• Gene name: Dual oxidase maturation factor 2
• Gene symbol: DUOXA2
• Synonyms (NCBI Gene): SIMNIPHOM, TDH5
• Chromosome: 15
• Chromosome location: 15q21.1
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs778410503	->A	Pathogenic	Coding sequence variant, stop gained
rs1555415049	C>G	Pathogenic	Stop gained, coding sequence variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	25761904
GO:0005783	Component	Endoplasmic reticulum	IDA	16651268, 19339556
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005829	Component	Cytosol	IDA	19339556
GO:0005886	Component	Plasma membrane	IDA	19339556
GO:0005886	Component	Plasma membrane	IGI	25761904
GO:0008104	Process	Intracellular protein localization	IGI	16651268, 19339556, 22814254
GO:0010729	Process	Positive regulation of hydrogen peroxide biosynthetic process	IDA	16651268
GO:0010729	Process	Positive regulation of hydrogen peroxide biosynthetic process	IMP	22814254
GO:0015031	Process	Protein transport	IEA
GO:0016020	Component	Membrane	IBA
GO:0016020	Component	Membrane	IEA
GO:0019899	Function	Enzyme binding	IPI	19339556
GO:0031252	Component	Cell leading edge	IGI	19339556
GO:0042743	Process	Hydrogen peroxide metabolic process	IEA
GO:0045177	Component	Apical part of cell	IDA	25761904
GO:0050727	Process	Regulation of inflammatory response	IEA
GO:0051604	Process	Protein maturation	IGI	16651268
GO:2000147	Process	Positive regulation of cell motility	IDA	19339556
GO:2000609	Process	Regulation of thyroid hormone generation	IEA

Other IDs

• MIM: 612772
• HGNC: 32698
• e!Ensembl: ENSG00000140274

Protein

• UniProt ID: Q1HG44
• Protein name: Dual oxidase maturation factor 2 (Dual oxidase activator 2)
• Protein function: Required for the maturation and the transport from the endoplasmic reticulum to the plasma membrane of functional DUOX2. May play a role in thyroid hormone synthesis.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF10204	DuoxA	10 → 286	Dual oxidase maturation factor	Family

• Tissue specificity: TISSUE SPECIFICITY: Specifically expressed in thyroid. Also detected in salivary glands. {ECO:0000269|PubMed:16651268}.
• Sequence:

  MTLWNGVLPFYPQPRHAAGFSVPLLIVILVFLALAASFLLILPGIRGHSRWFWLVRVLLS
  LFIGAEIVAVHFSAEWFVGTVNTNTSYKAFSAARVTARVRLLVGLEGINITLTGTPVHQL
  NETIDYNEQFTWRLKENYAAEYANALEKGLPDPVLYLAEKFTPSSPCGLYHQYHLAGHYA
  SATLWVAFCFWLLSNVLLSTPAPLYGGLALLTTGAFALFGVFALASISSVPLCPLRLGSS
  ALTTQYGAAFWVTLATGVLCLFLGGAVVSLQYVRPSALRTLLDQSAKDCSQERGGSPLIL
  GDPLHKQAALPDLKCITTNL

• Sequence length: 320

Pathways

KEGG:

Thyroid hormone synthesis

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Familial thyroid dyshormonogenesis	Likely pathogenic; Pathogenic	rs4774518, rs778410503	RCV005357049 RCV005361226	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Thyroglobulin synthesis defect	Likely pathogenic; Pathogenic	rs4774518, rs377426710, rs2504803353, rs778410503, rs2504810072, rs1555415049, rs781126484, rs770148072, rs974496530	RCV000000473 RCV002283662 RCV002470451 RCV000490516 RCV003331954 RCV000660507 RCV001175131 RCV001248815 RCV001251192	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Congenital hypothyroidism	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
DUOXA2-related disorder	Conflicting classifications of pathogenicity; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
THYROID DYSHORMONOGENESIS 5	—	CTD, Disgenet, GWAS catalog, HPO CTD, Disgenet, GWAS catalog, HPO CTD, Disgenet, GWAS catalog, HPO CTD, Disgenet, GWAS catalog, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Carcinoma in Situ	Carcinoma in situ	Pubtator	32425884	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	18281478		★☆☆☆☆ Found in Text Mining only
Colitis	Colitis	BEFREE	29272487		★☆☆☆☆ Found in Text Mining only
Colitis Ulcerative	Ulcerative colitis	Pubtator	18700007, 32190668	Associate	★☆☆☆☆ Found in Text Mining only
Congenital exomphalos	Congenital Exomphalos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Hypothyroidism	Congenital Hypothyroidism	BEFREE	18042646, 21367925, 25675383, 26210446, 26709262, 26758695, 28541007, 28626131, 28648510, 30110704, 31428054		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Congenital Hypothyroidism	Congenital hypothyroidism	Pubtator	18042646, 26709262, 26758695, 28541007, 31044655, 32425884, 34200080, 40362701	Associate	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Familial thyroid dyshormonogenesis	Thyroid Dyshormonogenesis	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypersomnia	Hypersomnia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	BEFREE	20407074, 23292166, 25675383		★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	Pubtator	21367925	Associate	★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Macroglossia	Macroglossia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	18281478		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	21321110, 31548328	Associate	★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	20395558	Associate	★☆☆☆☆ Found in Text Mining only
Thyroid Dyshormonogenesis 1	Thyroid dyshormonogenesis	Pubtator	18042646, 33692749	Associate	★☆☆☆☆ Found in Text Mining only
Thyroid Dyshormonogenesis 1	Thyroid Dyshormonogenesis	ORPHANET_DG	20537182, 21543982		★☆☆☆☆ Found in Text Mining only
Thyroid Dyshormonogenesis 1	Thyroid dyshormonogenesis	Pubtator	34539567	Stimulate	★☆☆☆☆ Found in Text Mining only
Thyroid Dyshormonogenesis 5	Thyroid Dyshormonogenesis	CLINVAR_DG	18042646, 23292166		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid Dyshormonogenesis 5	Thyroid Dyshormonogenesis	UNIPROT_DG	18042646, 25675383		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid Dyshormonogenesis 5	Thyroid Dyshormonogenesis	GENOMICS_ENGLAND_DG	27349010		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid Dyshormonogenesis 5	Thyroid Dyshormonogenesis	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Transient hypothyroxinaemia of prematurity	Transient Hypothyroxinaemia Of Prematurity	BEFREE	18765513, 20187165		★☆☆☆☆ Found in Text Mining only
Transient hypothyroxinaemia of prematurity	Transient Hypothyroxinaemia Of Prematurity	GENOMICS_ENGLAND_DG	27349010		★☆☆☆☆ Found in Text Mining only
Ulcerative Colitis	Ulcerative colitis	BEFREE	24492313		★☆☆☆☆ Found in Text Mining only