DUOXA2

dual oxidase maturation factor 2

Basic information

Region (hg38): 15:45114326-45118421

Links

ENSG00000140274 ∙ NCBI:405753 ∙ OMIM:612772 ∙ HGNC:32698 ∙ Uniprot:Q1HG44 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• thyroid dyshormonogenesis 5 (Moderate), mode of inheritance: AR
• familial thyroid dyshormonogenesis (Supportive), mode of inheritance: AR
• thyroid dyshormonogenesis 5 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thyroid dyshormonogenesis 5	AR	Endocrine	Medical treatment of hypothyroidism (eg, with T4) can be effective	Endocrine	18042646; 21367925; 23292166

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DUOXA2 gene.

• Thyroglobulin synthesis defect (4 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DUOXA2 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			2	6	5	13
missense		2	18	1	2	23
nonsense	3	1				4
start loss						0
frameshift	2	1	1		1	5
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	2	3
non coding			2	1	12	15
Total	5	4	23	8	20

Highest pathogenic variant AF is 0.0000788

Variants in DUOXA2

This is a list of pathogenic ClinVar variants found in the DUOXA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-45114520-C-T			Benign (Jul 10, 2018)
15-45114612-C-CTG			Pathogenic (Sep 18, 2020)
15-45114656-C-T			Benign (Dec 31, 2019)
15-45114657-G-A		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
15-45114683-C-G		not specified	Uncertain significance (Nov 20, 2023)
15-45114695-G-GT		Thyroglobulin synthesis defect	Pathogenic/Likely pathogenic (Feb 08, 2018)
15-45114714-AGCTTCCT-A		Thyroglobulin synthesis defect	Likely pathogenic (-)
15-45114723-C-T			Benign (Jul 06, 2018)
15-45114735-G-T		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
15-45114741-C-T		Inborn genetic diseases	Uncertain significance (Jul 02, 2024)
15-45114846-C-A			Benign (Jul 05, 2018)
15-45115769-C-T			Benign (Jul 06, 2018)
15-45115800-G-A		not specified	Uncertain significance (Jul 24, 2023)
15-45115854-T-A		Inborn genetic diseases	Uncertain significance (Mar 14, 2023)
15-45115858-T-C		Thyroglobulin synthesis defect • Congenital hypothyroidism • Inborn genetic diseases • DUOXA2-related disorder	Conflicting classifications of pathogenicity (May 09, 2023)
15-45116146-G-C		Thyroglobulin synthesis defect	Pathogenic/Likely pathogenic (Mar 29, 2024)
15-45116146-G-T		Thyroglobulin synthesis defect	Likely pathogenic (Sep 01, 2022)
15-45116198-C-T		not specified	Uncertain significance (Sep 13, 2024)
15-45116210-C-T		Inborn genetic diseases	Uncertain significance (Jun 21, 2022)
15-45116214-TC-T		Thyroglobulin synthesis defect	Pathogenic (May 06, 2021)
15-45116216-C-G		not specified • Thyroglobulin synthesis defect	Benign (May 28, 2019)
15-45116221-G-A			Benign (Dec 31, 2019)
15-45116493-C-G			Benign (Jul 09, 2018)
15-45116501-C-T		not specified • Thyroglobulin synthesis defect	Benign (-)
15-45116512-A-G		not specified • Thyroglobulin synthesis defect	Benign (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DUOXA2	protein_coding	protein_coding	ENST00000323030	6	4101

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.27e-15	0.000844	125483	0	265	125748	0.00105

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.05	228	188	1.22	0.0000114	2011
Missense in Polyphen		79	62.868	1.2566		746
Synonymous	0.294	85	88.5	0.960	0.00000619	709
Loss of Function	-1.69	19	12.5	1.52	5.53e-7	128

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000710	0.000691
Ashkenazi Jewish	0.00984	0.00987
East Asian	0.00525	0.00507
Finnish	0.00	0.00
European (Non-Finnish)	0.000354	0.000352
Middle Eastern	0.00525	0.00507
South Asian	0.000229	0.000229
Other	0.00166	0.00163

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:16651268}.
• Disease: DISEASE: Thyroid dyshormonogenesis 5 (TDH5) [MIM:274900]: A disorder due to thyroid dyshormonogenesis, causing hypothyroidism, goiter, and variable mental deficits derived from unrecognized and untreated hypothyroidism. {ECO:0000269|PubMed:18042646, ECO:0000269|PubMed:25675383}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Thyroid hormone synthesis - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.704
• rvis_EVS: -0.43
• rvis_percentile_EVS: 25.37

Haploinsufficiency Scores

• pHI: 0.0374
• hipred: N
• hipred_score: 0.207
• ghis: 0.488

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.461

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Duoxa2
• Phenotype: craniofacial phenotype; immune system phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; limbs/digits/tail phenotype; skeleton phenotype

Gene ontology

• Biological process: protein localization;positive regulation of hydrogen peroxide biosynthetic process;protein transport;cellular protein localization;hydrogen peroxide metabolic process;regulation of inflammatory response;protein maturation;positive regulation of cell motility;regulation of thyroid hormone generation
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;plasma membrane;integral component of membrane;cell leading edge;apical part of cell
• Molecular function: protein binding;enzyme binding