GeneBe

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Thyroid dyshormonogenesis 5AREndocrineMedical treatment of hypothyroidism (eg, with T4) can be effectiveEndocrine18042646; 21367925; 23292166

ClinVar

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

  • Inborn_genetic_diseases (33 variants)
  • not_provided (31 variants)
  • Thyroglobulin_synthesis_defect (28 variants)
  • not_specified (13 variants)
  • DUOXA2-related_disorder (5 variants)
  • Congenital_hypothyroidism (2 variants)
  • Familial_thyroid_dyshormonogenesis (2 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. These statistics are base on transcript: NM_000207581.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
6
clinvar
5
clinvar
 13
missense
1
clinvar
3
clinvar
33
clinvar
5
clinvar
1
clinvar
 43
nonsense
4
clinvar
5
clinvar
 9
start loss
1
 1
frameshift
3
clinvar
7
clinvar
2
clinvar
1
clinvar
 13
splice donor/acceptor (+/-2bp)
6
clinvar
1
clinvar
 7
Total 8 22 38 11 7

Highest pathogenic variant AF is 0.000112931

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
DUOXA2protein_codingprotein_codingENST00000323030 64101
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.27e-150.00084412548302651257480.00105
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-1.052281881.220.00001142011
Missense in Polyphen7962.8681.2566746
Synonymous0.2948588.50.9600.00000619709
Loss of Function-1.691912.51.525.53e-7128

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0007100.000691
Ashkenazi Jewish0.009840.00987
East Asian0.005250.00507
Finnish0.000.00
European (Non-Finnish)0.0003540.000352
Middle Eastern0.005250.00507
South Asian0.0002290.000229
Other0.001660.00163

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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