DUOX2

dual oxidase 2, the group of EF-hand domain containing

Basic information

Region (hg38): 15:45092649-45114172

Links

ENSG00000140279 ∙ NCBI:50506 ∙ OMIM:606759 ∙ HGNC:13273 ∙ Uniprot:Q9NRD8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial thyroid dyshormonogenesis (Supportive), mode of inheritance: AR
• thyroid dyshormonogenesis 6 (Definitive), mode of inheritance: AR
• thyroid dyshormonogenesis 6 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thyroid dyshormonogenesis 6	AD/AR	Endocrine	Individuals may manifest with congenital or subclinical hypothyroidism, and medical treatment (with thyroid hormone replacement) may be effective	Endocrine	12110737; 16134168; 21565790; 23239635; 23457309
Heterozygous variants have been reported as typically resulting in transient congenital hypothyroidism, while bi-allelic variants have been described as more frequently causing more severe and permanent forms of disease

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DUOX2 gene.

• not provided (1178 variants)
• Thyroid dyshormonogenesis 6 (279 variants)
• Inborn genetic diseases (71 variants)
• not specified (38 variants)
• DUOX2-related condition (12 variants)
• Congenital hypothyroidism (8 variants)
• Nongoitrous Euthyroid Hyperthyrotropinemia (5 variants)
• Familial thyroid dyshormonogenesis (2 variants)
• See cases (2 variants)
• Abnormal circulating thyroid hormone concentration (1 variants)
• Meckel syndrome, type 11 (1 variants)
• Idiopathic basal ganglia calcification 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DUOX2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			17	204	7	228
missense	2	6	517	30	6	561
nonsense	28	11	3			42
start loss						0
frameshift	35	16				51
inframe indel	1		10			11
splice donor/acceptor (+/-2bp)	2	24	1			27
splice region			37	32	2	71
non coding			40	141	63	244
Total	68	57	588	375	76

Highest pathogenic variant AF is 0.000348

Variants in DUOX2

This is a list of pathogenic ClinVar variants found in the DUOX2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-45092712-C-T		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 13, 2018)
15-45092713-G-A		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 13, 2018)
15-45092722-C-T		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 15, 2018)
15-45092793-T-C		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 13, 2018)
15-45092798-C-T		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 12, 2018)
15-45092835-T-G		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 13, 2018)
15-45092906-A-T		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 13, 2018)
15-45092920-G-A		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 12, 2018)
15-45092947-G-A		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 13, 2018)
15-45093005-G-A		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 13, 2018)
15-45093086-C-T		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 13, 2018)
15-45093236-C-A		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 12, 2018)
15-45093293-C-T		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 13, 2018)
15-45093298-A-T		Thyroid dyshormonogenesis 6	Benign (Jan 13, 2018)
15-45093372-G-T		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 13, 2018)
15-45093385-G-A		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 13, 2018)
15-45093428-C-T		Thyroid dyshormonogenesis 6	Benign (Jan 12, 2018)
15-45093485-C-T		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 13, 2018)
15-45093526-G-A		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 13, 2018)
15-45093559-G-A		Thyroid dyshormonogenesis 6	Likely benign (Jan 12, 2018)
15-45093565-T-C		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 12, 2018)
15-45093672-C-T		Thyroid dyshormonogenesis 6	Benign (Jan 13, 2018)
15-45093675-C-T		Thyroid dyshormonogenesis 6	Uncertain significance (Jan 13, 2018)
15-45093697-A-G		Thyroid dyshormonogenesis 6	Benign (Jan 13, 2018)
15-45093718-C-T		Thyroid dyshormonogenesis 6	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DUOX2	protein_coding	protein_coding	ENST00000603300	33	21695

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.50e-56	1.07e-9	124411	9	1328	125748	0.00533

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.17	950	854	1.11	0.0000529	10017
Missense in Polyphen		386	355.53	1.0857		4215
Synonymous	-1.59	387	349	1.11	0.0000206	3117
Loss of Function	-0.464	82	77.6	1.06	0.00000431	848

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00578	0.00576
Ashkenazi Jewish	0.000797	0.000794
East Asian	0.0150	0.0148
Finnish	0.0118	0.0118
European (Non-Finnish)	0.00467	0.00462
Middle Eastern	0.0150	0.0148
South Asian	0.00328	0.00321
Other	0.00441	0.00441

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a role in thyroid hormones synthesis and lactoperoxidase-mediated antimicrobial defense at the surface of mucosa. May have its own peroxidase activity through its N-terminal peroxidase-like domain. {ECO:0000269|PubMed:12824283}.
• Disease: DISEASE: Thyroid dyshormonogenesis 6 (TDH6) [MIM:607200]: A disorder due to a defective conversion of accumulated iodide to organically bound iodine. The iodide organification defect can be partial or complete. {ECO:0000269|PubMed:12110737, ECO:0000269|PubMed:16134168, ECO:0000269|PubMed:16322276, ECO:0000269|PubMed:20187165}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in DUOX2 may play a role in the pathogenesis of very early onset inflammatory bowel disease (VEOIBD), a chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology diagnosed before 6 years of age. VEOIBD is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but the phenotype of children with onset of Crohn disease occurring younger than the age of 10 is predominantly colonic, with a lower risk of ileal disease. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints. {ECO:0000269|PubMed:26301257}.
• Pathway: Thyroid hormone synthesis - Homo sapiens (human);Thyroid hormone synthesis;Nucleotide-binding Oligomerization Domain (NOD) pathway;Metabolism of amino acids and derivatives;Metabolism;Thyroxine biosynthesis;Amine-derived hormones (Consensus)

Recessive Scores

• pRec: 0.215

Intolerance Scores

• loftool: 0.135
• rvis_EVS: 0.23
• rvis_percentile_EVS: 68.52

Haploinsufficiency Scores

• pHI: 0.151
• hipred: N
• hipred_score: 0.241
• ghis: 0.433

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.474

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Duox2
• Phenotype: endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; reproductive system phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype

Zebrafish Information Network

• Gene name: duox
• Affected structure: neutrophil
• Phenotype tag: abnormal
• Phenotype quality: decreased process quality

Gene ontology

• Biological process: thyroid hormone generation;defense response;response to oxidative stress;fertilization;response to virus;cytokine-mediated signaling pathway;bone mineralization;thyroid gland development;multicellular organism growth;cuticle development;hormone biosynthetic process;superoxide anion generation;hydrogen peroxide catabolic process;inner ear development;adenohypophysis morphogenesis;hydrogen peroxide biosynthetic process;response to cAMP;oxidation-reduction process;positive regulation of wound healing;cellular oxidant detoxification;positive regulation of cell motility
• Cellular component: endoplasmic reticulum;cytosol;plasma membrane;cell surface;integral component of membrane;apical plasma membrane;cell junction;cell leading edge;NADPH oxidase complex;apical part of cell;extracellular exosome
• Molecular function: peroxidase activity;calcium ion binding;protein binding;NAD(P)H oxidase activity;superoxide-generating NADPH oxidase activity;heme binding