DUOXA2

Summary

DUOXA2 (dual oxidase maturation factor 2, HGNC:32698) is a protein-coding gene on chromosome 15q21.1, encoding Dual oxidase maturation factor 2 (Q1HG44). Required for the maturation and transport of functional DUOX2 from the endoplasmic reticulum to the plasma membrane.

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.

Source: NCBI Gene 405753 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thyroid dyshormonogenesis 5 (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 104 total — 8 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 34
• MANE Select transcript: NM_207581

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32698
Approved symbol	DUOXA2
Name	dual oxidase maturation factor 2
Location	15q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000140274
Ensembl biotype	protein_coding
OMIM	612772
Entrez	405753

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000323030, ENST00000350243, ENST00000491993, ENST00000958164

RefSeq mRNA: 1 — MANE Select: NM_207581 NM_207581

CCDS: CCDS10118

Canonical transcript exons

ENST00000323030 — 6 exons

Exon	Start	End
ENSE00001917503	45117716	45118421
ENSE00001924933	45114326	45114752
ENSE00003503880	45115799	45115856
ENSE00003593360	45117091	45117305
ENSE00003614738	45116124	45116258
ENSE00003691223	45116516	45116729

Expression profiles

Bgee: expression breadth ubiquitous, 121 present calls, max score 95.90.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3798 / max 174.4189, expressed in 52 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146423	0.3798	52

Top tissues by expression

209 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	95.90	silver quality
nasal cavity epithelium	UBERON:0005384	94.48	gold quality
gall bladder	UBERON:0002110	92.34	gold quality
buccal mucosa cell	CL:0002336	92.33	gold quality
epithelial cell of pancreas	CL:0000083	90.48	gold quality
palpebral conjunctiva	UBERON:0001812	88.86	gold quality
right lobe of thyroid gland	UBERON:0001119	86.71	gold quality
islet of Langerhans	UBERON:0000006	86.03	gold quality
lower esophagus mucosa	UBERON:0035834	85.00	gold quality
left lobe of thyroid gland	UBERON:0001120	84.33	gold quality
parotid gland	UBERON:0001831	83.84	silver quality
thyroid gland	UBERON:0002046	83.66	gold quality
mucosa of stomach	UBERON:0001199	83.59	gold quality
upper arm skin	UBERON:0004263	81.93	gold quality
heart right ventricle	UBERON:0002080	81.50	gold quality
esophagus mucosa	UBERON:0002469	78.60	gold quality
vermiform appendix	UBERON:0001154	77.32	gold quality
esophagus squamous epithelium	UBERON:0006920	76.10	gold quality
pylorus	UBERON:0001166	75.89	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	75.76	gold quality
caecum	UBERON:0001153	75.21	gold quality
biceps brachii	UBERON:0001507	75.13	gold quality
vagina	UBERON:0000996	74.13	gold quality
body of stomach	UBERON:0001161	73.99	gold quality
myocardium	UBERON:0002349	73.83	gold quality
vena cava	UBERON:0004087	72.79	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	72.66	gold quality
vastus lateralis	UBERON:0001379	72.18	gold quality
body of tongue	UBERON:0011876	71.78	silver quality
kidney epithelium	UBERON:0004819	71.72	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HAND2

miRNA regulators (miRDB)

5 targeting DUOXA2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6787-5P	97.54	63.85	457
HSA-MIR-1289	97.46	65.37	655
HSA-MIR-10396B-5P	94.99	63.57	358
HSA-MIR-1908-5P	94.99	63.41	352
HSA-MIR-663A	94.99	63.54	378

Literature-anchored findings (GeneRIF, showing 19)

• co-expression of DUOXA2, an ER-resident transmembrane protein, allows ER-to-Golgi transition, maturation, and translocation to the plasma membrane of functional DUOX2 in a heterologous system (PMID:16651268)
• DUOXA2 allows rapid ER exit of folded DUOX2 or enhanced degradation of mutant DUOX2 proteins not competent for ER exit. (PMID:17374849)
• Results provide evidence for the critical role of DUOXA2 in thyroid hormonogenesis. Biallelic DUOXA2 mutations are a novel genetic event in permanent congenital hypothroidism. (PMID:18042646)
• The five gene transcripts (aldolase B, elafin, MST-1, simNIPhom and SLC6A14) were changed in patients with ulcerative colitis, and were related to the disease activity. (PMID:18700007)
• Heterodimerization controls localization of Duox-DuoxA NADPH oxidases in airway cells. (PMID:19339556)
• Up-regulation and sustained activation of Stat1 are essential for interferon-gamma (IFN-gamma)-induced dual oxidase 2 (Duox2) and dual oxidase A2 (DuoxA2) expression in human pancreatic cancer cell lines. (PMID:21321110)
• Two functionally important single-nucleotide polymorphisms within the promoter differentially regulate DUOX2/DUOXA2 transcription in response to exogenous double-stranded DNA. (PMID:22592922)
• Native DUOXA2 would constrain DUOX2 to produce H(2)O(2). (PMID:22814254)
• The DUOX-expressing model, the human intestinal Caco-2 cell line, expression of DUOXA2 mRNA was also positively modulated by IL-4 and IL-13. (PMID:23010498)
• This study is the first to report a novel c.413-414insA (Y138X) mutation for congenital hypothyroidism, thereby expanding the mutational spectrum of the DUOXA2 gene. (PMID:23292166)
• DUOXA2 is Significantly Upregulated in Active Ulcerative Colitis and during Progression to Dysplasia. (PMID:24492313)
• a novel DUOXA2 mutation (I26M) causing congenital hypothyroidism with goiter, which affected H2O2 generation but did not alter the protein expression levels, further confirming the essential role of DUOXA2 in thyroid hormone synthesis. (PMID:25675383)
• The folding of DUOX2 appears to be a key event in the trafficking of the DUOX2/DUOXA2 complex as it promotes an appropriate conformation of the N-terminal region, which is propitious to subsequent covalent interactions with the maturation factor, DUOXA2. (PMID:25761904)
• inactivating mutations in the DUOXA2 (p.Y246X) and DUOX2 (p.R885Q) genes were identified in a set of dizygotic twins with congenital hypothyroidism (PMID:27349010)
• DUOXA2 gene mutation is a common molecular pathogenic basis for congenital hypothyroidism children with suspected thyroid dyshormonogenesis in Guangzhou. (PMID:28100324)
• This study reports the pedigree with goitrous congenital hypothyroidism (GCH) due to the coexistence of heterozygous mutations in the DUOX2 and DUOXA2 genes. (PMID:28541007)
• DUOX2/DUOXA2 Mutations Frequently Cause Congenital Hypothyroidism that Evades Detection on Newborn Screening in the United Kingdom. (PMID:31044655)
• H2O2 produced by the Duox2/DuoxA2 cell surface enzymatic complex could provoke potential mutagenic DNA damage. (PMID:31513783)
• DUOX2 and DUOXA2 Variants Confer Susceptibility to Thyroid Dysgenesis and Gland-in-situ With Congenital Hypothyroidism. (PMID:32425884)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	duox2	ENSDARG00000078962
mus_musculus	Duoxa2	ENSMUSG00000027225
rattus_norvegicus	Duoxa2	ENSRNOG00000017805
drosophila_melanogaster	mol	FBGN0086711
caenorhabditis_elegans		WBGENE00015519

Paralogs (1): DUOXA1 (ENSG00000140254)

Protein

Protein identifiers

Dual oxidase maturation factor 2 — Q1HG44 (reviewed: Q1HG44)

Alternative names: Dual oxidase activator 2

All UniProt accessions (1): Q1HG44

UniProt curated annotations — full annotation on UniProt →

Function. Required for the maturation and transport of functional DUOX2 from the endoplasmic reticulum to the plasma membrane. Recruits DUOX2 to the apical cell membrane.

Subunit / interactions. Heterodimer with DUOXA2; disulfide-linked. Interacts with CSNK1G2.

Subcellular location. Endoplasmic reticulum membrane. Apical cell membrane.

Tissue specificity. Specifically expressed in thyroid. Also detected in salivary glands.

Post-translational modifications. N-glycosylated; this is required for DUOXA2 protein stability but not for interaction with DUOX2 or for localization of DUOX2 to the apical cell membrane.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the DUOXA family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q1HG44-1	1	yes
Q1HG44-2	2

RefSeq proteins (1): NP_997464* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018469	Dual_oxidase_maturation_fac	Family

Pfam: PF10204

UniProt features (24 total): topological domain 6, transmembrane region 5, glycosylation site 3, mutagenesis site 3, disulfide bond 2, splice variant 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q1HG44-F1	83.29	0.58

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 167, 233

Glycosylation sites (3): 84, 109, 121

Mutagenesis-validated functional residues (3):

Position	Phenotype
84	reduces duoxa2 stability but does not affect interaction with duox1 or targeting of duox1 to the apical cell membrane; w
109	reduces duoxa2 stability but does not affect interaction with duox1 or targeting of duox1 to the apical cell membrane; w
121	reduces duoxa2 stability but does not affect interaction with duox1 or targeting of duox1 to the apical cell membrane; w

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-209968	Thyroxine biosynthesis

MSigDB gene sets: 170 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, GOBP_INFLAMMATORY_RESPONSE, LFA1_Q6, GOBP_POSITIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_THYROID_HORMONE_METABOLIC_PROCESS, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_REACTIVE_OXYGEN_SPECIES_BIOSYNTHETIC_PROCESS, GOBP_PROTEIN_MATURATION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, TATA_C, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (8): intracellular protein localization (GO:0008104), positive regulation of hydrogen peroxide biosynthetic process (GO:0010729), protein transport (GO:0015031), hydrogen peroxide metabolic process (GO:0042743), regulation of inflammatory response (GO:0050727), protein maturation (GO:0051604), positive regulation of cell motility (GO:2000147), regulation of thyroid hormone generation (GO:2000609)

GO Molecular Function (2): enzyme binding (GO:0019899), protein binding (GO:0005515)

GO Cellular Component (7): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), cell leading edge (GO:0031252), apical part of cell (GO:0045177)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of amine-derived hormones	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	2
macromolecule localization	1
regulation of hydrogen peroxide biosynthetic process	1
hydrogen peroxide biosynthetic process	1
positive regulation of reactive oxygen species biosynthetic process	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
reactive oxygen species metabolic process	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
gene expression	1
protein metabolic process	1
positive regulation of locomotion	1
positive regulation of cellular process	1
cell motility	1
regulation of cell motility	1
thyroid hormone generation	1
regulation of hormone metabolic process	1
protein binding	1
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

574 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUOXA2	DUOX2	Q9NRD8	997
DUOXA2	DUOX1	Q9NRD9	985
DUOXA2	IYD	Q6PHW0	952
DUOXA2	SLC5A5	Q92911	851
DUOXA2	SLC26A4	O43511	851
DUOXA2	TPO	P07202	770
DUOXA2	TG	P01266	740
DUOXA2	TSHR	P16473	660
DUOXA2	CYBB	P04839	659
DUOXA2	FOXE1	O00358	625
DUOXA2	NOXA1	Q86UR1	621
DUOXA2	NOXO1	Q8NFA2	611
DUOXA2	NOX5	Q96PH1	610
DUOXA2	NOX1	Q9Y5S8	609
DUOXA2	DUOXA1	Q1HG43	606

IntAct

9 interactions, top by confidence:

A	B	Type	Score
DUOX2	DUOXA2	psi-mi:“MI:0915”(physical association)	0.590
DUOXA2	PRKAR1B	psi-mi:“MI:0914”(association)	0.350
DUOXA2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
DUOXA2	CHRNB1	psi-mi:“MI:0914”(association)	0.350

BioGRID (50): CCPG1 (Affinity Capture-MS), MZT2B (Affinity Capture-MS), GPM6A (Affinity Capture-MS), ENTPD7 (Affinity Capture-MS), MFAP3 (Affinity Capture-MS), TMX4 (Affinity Capture-MS), PRKAR1B (Affinity Capture-MS), RNF149 (Affinity Capture-MS), DNAJC19 (Affinity Capture-MS), GLRB (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), SAMM50 (Affinity Capture-MS), KIAA0368 (Affinity Capture-MS), ECE1 (Affinity Capture-MS), MTX2 (Affinity Capture-MS)

ESM2 similar proteins: A0JP80, A1A5Z0, A5D6W6, A7YWN2, B2MVP8, B6CZ46, L5KLU7, O42153, O75783, O75908, O77759, O88908, P58872, P58873, P86243, Q1HG44, Q1KZG0, Q1XHX8, Q32LM8, Q49LS7, Q52KL1, Q5CZN0, Q5KR61, Q5T197, Q5TM67, Q5XIL6, Q6AX73, Q6AZ83, Q6MG14, Q6NSQ9, Q6P5W5, Q767L9, Q7TNJ2, Q7TQM4, Q80YU0, Q86VD9, Q8AVI9, Q8CIP5, Q8IWX5, Q8IXM6

Diamond homologs: Q0P4G7, Q1HG43, Q1HG44, Q6DDK3, Q8VE49, Q9D311, P34298

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

104 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	14
Uncertain significance	32
Likely benign	16
Benign	23

Top pathogenic / likely-pathogenic (22)

Variant ID	HGVS	Classification
1806167	NM_207581.4(DUOXA2):c.298del (p.Arg100fs)	Pathogenic
2581549	NM_207581.4(DUOXA2):c.573G>A (p.Trp191Ter)	Pathogenic
3577206	NM_207581.4(DUOXA2):c.37C>T (p.Gln13Ter)	Pathogenic
3577207	NM_207581.4(DUOXA2):c.136del (p.Arg46fs)	Pathogenic
504016	NM_207581.4(DUOXA2):c.10_11dup (p.Trp4fs)	Pathogenic
547935	NM_207581.4(DUOXA2):c.414C>G (p.Tyr138Ter)	Pathogenic
917857	NM_207581.4(DUOXA2):c.501C>A (p.Cys167Ter)	Pathogenic
972709	NM_207581.4(DUOXA2):c.604G>A (p.Ala202Thr)	Pathogenic
1705348	NM_207581.4(DUOXA2):c.228G>T (p.Trp76Cys)	Likely pathogenic
3383175	NM_207581.4(DUOXA2):c.113_119del (p.Phe38fs)	Likely pathogenic
3577205	NM_207581.4(DUOXA2):c.1A>G (p.Met1Val)	Likely pathogenic
3577208	NM_207581.4(DUOXA2):c.147+1G>T	Likely pathogenic
3577209	NM_207581.4(DUOXA2):c.205+1G>A	Likely pathogenic
3577210	NM_207581.4(DUOXA2):c.205+1G>T	Likely pathogenic
3577211	NM_207581.4(DUOXA2):c.340+1G>A	Likely pathogenic
3577212	NM_207581.4(DUOXA2):c.382G>T (p.Glu128Ter)	Likely pathogenic
3577213	NM_207581.4(DUOXA2):c.396G>A (p.Trp132Ter)	Likely pathogenic
3577214	NM_207581.4(DUOXA2):c.465_466dup (p.Tyr156fs)	Likely pathogenic
3577215	NM_207581.4(DUOXA2):c.611T>C (p.Leu204Pro)	Likely pathogenic
3577216	NM_207581.4(DUOXA2):c.753G>A (p.Trp251Ter)	Likely pathogenic
3577217	NM_207581.4(DUOXA2):c.768del (p.Gly257fs)	Likely pathogenic
3577219	NM_207581.4(DUOXA2):c.769+2T>A	Likely pathogenic

SpliceAI

897 predictions. Top by Δscore:

Variant	Effect	Δscore
15:45116121:C:G	acceptor_gain	1.0000
15:45116122:A:AG	acceptor_gain	1.0000
15:45116123:G:GG	acceptor_gain	1.0000
15:45116123:GC:G	acceptor_gain	1.0000
15:45116123:GCT:G	acceptor_gain	1.0000
15:45116123:GCTGT:G	acceptor_gain	1.0000
15:45116514:A:AG	acceptor_gain	1.0000
15:45116515:G:GG	acceptor_gain	1.0000
15:45116728:TGGTA:T	donor_loss	1.0000
15:45116729:GGTA:G	donor_loss	1.0000
15:45116730:G:GG	donor_gain	1.0000
15:45117089:AG:A	acceptor_gain	1.0000
15:45117090:GG:G	acceptor_gain	1.0000
15:45117271:G:GG	donor_gain	1.0000
15:45117698:C:CA	acceptor_gain	1.0000
15:45117715:GGC:G	acceptor_gain	1.0000
15:45115528:G:T	donor_gain	0.9900
15:45116105:C:A	acceptor_gain	0.9900
15:45116122:AGCT:A	acceptor_gain	0.9900
15:45116123:GCTG:G	acceptor_gain	0.9900
15:45116510:CCACA:C	acceptor_loss	0.9900
15:45116511:CACAG:C	acceptor_loss	0.9900
15:45116513:CAGG:C	acceptor_loss	0.9900
15:45116514:AG:A	acceptor_gain	0.9900
15:45116514:AGG:A	acceptor_gain	0.9900
15:45116515:GG:G	acceptor_gain	0.9900
15:45116515:GGG:G	acceptor_gain	0.9900
15:45116725:CTATG:C	donor_gain	0.9900
15:45116726:TATG:T	donor_gain	0.9900
15:45116727:ATG:A	donor_gain	0.9900

AlphaMissense

2036 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:45115829:A:C	S60R	0.980
15:45115831:T:A	S60R	0.980
15:45115831:T:G	S60R	0.980
15:45114714:A:C	S37R	0.969
15:45114716:C:A	S37R	0.969
15:45114716:C:G	S37R	0.969
15:45117284:T:C	F250L	0.957
15:45117286:C:A	F250L	0.957
15:45117286:C:G	F250L	0.957
15:45116563:T:C	F130L	0.955
15:45116565:C:A	F130L	0.955
15:45116565:C:G	F130L	0.955
15:45116656:T:C	F161L	0.953
15:45116658:C:A	F161L	0.953
15:45116658:C:G	F161L	0.953
15:45116186:T:C	F90L	0.949
15:45116188:C:A	F90L	0.949
15:45116188:C:G	F90L	0.949
15:45116564:T:C	F130S	0.949
15:45117107:T:A	W191R	0.942
15:45117107:T:C	W191R	0.942
15:45114696:T:C	F31L	0.937
15:45114698:T:A	F31L	0.937
15:45114698:T:G	F31L	0.937
15:45116564:T:G	F130C	0.937
15:45116144:T:A	W76R	0.936
15:45116144:T:C	W76R	0.936
15:45116182:A:C	K88N	0.932
15:45116182:A:T	K88N	0.932
15:45116657:T:C	F161S	0.926

dbSNP variants (sampled 300 via entrez): RS1000680012 (15:45113560 T>C), RS1001930497 (15:45113283 C>G,T), RS1003208915 (15:45117461 G>A), RS1003547773 (15:45112455 C>CTCCTGT), RS1004632459 (15:45112894 C>A,G), RS1004744609 (15:45118791 C>A,T), RS1004751510 (15:45115184 A>G), RS1004822345 (15:45116495 T>A,C), RS1005295613 (15:45115578 C>G,T), RS1005352741 (15:45115289 G>A), RS1006350868 (15:45114041 C>T), RS1006476090 (15:45113660 G>A), RS1006548687 (15:45118547 T>A), RS1006710299 (15:45114327 G>T), RS1006775304 (15:45112773 C>A,T)

Disease associations

OMIM: gene MIM:612772 | disease phenotypes: MIM:274900, MIM:274400, MIM:607200

GenCC curated gene-disease

Disease	Classification	Inheritance
thyroid dyshormonogenesis 5	Strong	Autosomal recessive
familial thyroid dyshormonogenesis	Supportive	Autosomal recessive

Mondo (4): thyroid dyshormonogenesis 5 (MONDO:0010137), familial thyroid dyshormonogenesis (MONDO:0010132), congenital hypothyroidism (MONDO:0018612), thyroid dyshormonogenesis 6 (MONDO:0011792)

Orphanet (3): Familial thyroid dyshormonogenesis (Orphanet:95716), Congenital hypothyroidism (Orphanet:442), Genetic transient congenital hypothyroidism (Orphanet:226316)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000158	Macroglossia
HP:0000270	Delayed cranial suture closure
HP:0000282	Facial edema
HP:0000407	Sensorineural hearing impairment
HP:0000821	Hypothyroidism
HP:0000851	Congenital hypothyroidism
HP:0000853	Goiter
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001265	Hyporeflexia
HP:0001510	Growth delay
HP:0001537	Umbilical hernia
HP:0001662	Bradycardia
HP:0001939	Abnormality of metabolism/homeostasis
HP:0002019	Constipation
HP:0002045	Hypothermia
HP:0002925	Elevated circulating thyroid-stimulating hormone concentration
HP:0003265	Neonatal hyperbilirubinemia
HP:0004491	Large posterior fontanelle
HP:0005280	Depressed nasal bridge
HP:0005930	Abnormal epiphysis morphology
HP:0006579	Prolonged neonatal jaundice
HP:0008263	Thyroid defect in oxidation and organification of iodide
HP:0008828	Delayed proximal femoral epiphyseal ossification
HP:0008872	Feeding difficulties in infancy
HP:0011437	Maternal autoimmune disease
HP:0012758	Neurodevelopmental delay
HP:0025482	Positive perchlorate discharge test

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D003409	Congenital Hypothyroidism	C05.116.099.343.347; C05.116.132.256; C16.320.240.625; C19.297.155; C19.874.482.281
C564766	Thyroid Dyshormonogenesis 1 (supp.)
C562771	Thyroid Dyshormonogenesis 5 (supp.)
C564608	Thyroid Dyshormonogenesis 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
terbufos	increases methylation	1
sodium arsenite	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Fonofos	increases methylation	1
Latex	increases expression	1
Methotrexate	decreases expression	1
Nickel	increases expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Palmitic Acid	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

24 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05228184	PHASE4	TERMINATED	Use of Tirosint®-SOL or Tablet Formulations of Levothyroxine in Pediatric Patients With Congenital Hypothyroidism (CH)
NCT05371262	PHASE4	COMPLETED	Influence of Initial Levothyroxine Dose on Neurodevelopmental and Growth Outcomes in Congenital Hypothyroidism
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT00403390	Not specified	COMPLETED	Generic vs. Name-Brand Levothyroxine
NCT00493103	Not specified	COMPLETED	TG Gene Mutations and Congenital Hypothyroidism
NCT00497575	Not specified	COMPLETED	Diagnosis and Follow-up of Patients With Subclinical Hypothyroidism
NCT00505479	Not specified	UNKNOWN	Iodine Status in Pregnant Women and Their Newborns: is Congenital Hypothyroidism Related to Iodine Deficiency in Pregnancy?
NCT01223638	Not specified	WITHDRAWN	The Prevalence of Hearing Loss Among Children With Congenital Hypothyroidism
NCT01349634	Not specified	COMPLETED	The Effects of Iodized Salt on Cognitive Development in Ethiopia
NCT01488721	Not specified	COMPLETED	Clinical Evaluation of NeoPlex4 Assay and NeoPlex System
NCT01916018	Not specified	COMPLETED	Clinical and Genetic Analysis in Congenital Hypothyroidism Due to Thyroid Dysgenesis.
NCT02307175	Not specified	COMPLETED	A Study of 99m Tc Pertechnetate Produced in High Energy Cyclotron in Patients With Thyroid Scan Indication
NCT02374593	Not specified	COMPLETED	Targeted Levothyroxine Dosing in Infants With Congenital Hypothyroidism
NCT04712760	Not specified	UNKNOWN	Congenital Hypothyroidism in Children With Eutopic Gland or Thyroid Hemiagenesis: Predictive Factors for Transient vs Permanent Hypothyroidism.
NCT04734457	Not specified	UNKNOWN	Final Height in Patients With CH Diagnosed by the Screening
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT06724224	Not specified	RECRUITING	Comparison of Levothyroxine Formulations in the Treatment of Congenital Hypothyroidism
NCT06728735	Not specified	RECRUITING	Role of Next Generation Sequencing in the Etiological Diagnosis of Permanent Congenital Hypothyroidism With in Situ Thyroid
NCT06864039	Not specified	ENROLLING_BY_INVITATION	Quality of Life and Long-term Outcome of Adequately Treated Congenital Hypothyroidism
NCT06864351	Not specified	RECRUITING	Prospective Evaluation of OptiThyDose
NCT07126353	Not specified	NOT_YET_RECRUITING	Metabolic Risk Assessment in Prepubertal Children With Congenital Hypothyroidism
NCT07280104	Not specified	RECRUITING	Infants With Primary Congenital Hypothyroidism and Development
NCT07425028	Not specified	NOT_YET_RECRUITING	Evaluation of an Intensified Systematic Screening for Congenital Hypothyroidism in Premature Newborns
NCT07579988	Not specified	NOT_YET_RECRUITING	Ultrasound Measurement of Thyroid Volume in Term Newborns