TPO

Summary

TPO (thyroid peroxidase, HGNC:12015) is a protein-coding gene on chromosome 2p25.3, encoding Thyroid peroxidase (P07202). Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4).

This gene encodes a membrane-bound glycoprotein. The encoded protein acts as an enzyme and plays a central role in thyroid gland function. The protein functions in the iodination of tyrosine residues in thyroglobulin and phenoxy-ester formation between pairs of iodinated tyrosines to generate the thyroid hormones, thyroxine and triiodothyronine. Mutations in this gene are associated with several disorders of thyroid hormonogenesis, including congenital hypothyroidism, congenital goiter, and thyroid hormone organification defect IIA. Multiple transcript variants encoding distinct isoforms have been identified for this gene, but the full-length nature of some variants has not been determined.

Source: NCBI Gene 7173 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thyroid dyshormonogenesis 2A (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 511 total — 43 pathogenic, 37 likely-pathogenic
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_001206744

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12015
Approved symbol	TPO
Name	thyroid peroxidase
Location	2p25.3
Locus type	gene with protein product
Status	Approved
Aliases	TPX
Ensembl gene	ENSG00000115705
Ensembl biotype	protein_coding
OMIM	606765
Entrez	7173

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 20 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000329066, ENST00000345913, ENST00000346956, ENST00000382198, ENST00000382201, ENST00000382269, ENST00000422464, ENST00000423320, ENST00000425083, ENST00000446278, ENST00000462973, ENST00000469607, ENST00000479902, ENST00000497517, ENST00000539820, ENST00000650224, ENST00000898234, ENST00000898235, ENST00000898236, ENST00000898237, ENST00000961833, ENST00000961834, ENST00000961835, ENST00000961836, ENST00000961837

RefSeq mRNA: 6 — MANE Select: NM_001206744 NM_000547, NM_001206744, NM_001206745, NM_175719, NM_175721, NM_175722

CCDS: CCDS1643, CCDS1644, CCDS1646

Canonical transcript exons

ENST00000329066 — 17 exons

Exon	Start	End
ENSE00001145717	1495989	1496197
ENSE00001145731	1487821	1487991
ENSE00001145739	1477086	1477604
ENSE00001145742	1456076	1456282
ENSE00001145744	1453694	1453823
ENSE00001145749	1436252	1436384
ENSE00001145752	1433438	1433607
ENSE00001145756	1423045	1423129
ENSE00001363126	1540594	1540723
ENSE00001363154	1496595	1496765
ENSE00001835030	1413463	1413545
ENSE00002729849	1414408	1414502
ENSE00003469072	1484596	1484854
ENSE00003667852	1493802	1494039
ENSE00003671696	1503948	1504079
ENSE00003681502	1516883	1516982
ENSE00003896361	1542421	1543673

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 99.89.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 4.2661 / max 4421.2613, expressed in 72 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18560	3.7808	13
18559	0.1707	49
18558	0.1436	44
18563	0.0527	5
18593	0.0249	3
18594	0.0186	2
18568	0.0184	2
18564	0.0165	5
18592	0.0080	4
18562	0.0079	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left lobe of thyroid gland	UBERON:0001120	99.89	gold quality
thyroid gland	UBERON:0002046	99.87	gold quality
right lobe of thyroid gland	UBERON:0001119	99.86	gold quality
spleen	UBERON:0002106	90.11	gold quality
sural nerve	UBERON:0015488	89.50	gold quality
apex of heart	UBERON:0002098	87.94	gold quality
subcutaneous adipose tissue	UBERON:0002190	84.79	gold quality
heart left ventricle	UBERON:0002084	83.60	gold quality
adipose tissue	UBERON:0001013	82.93	gold quality
mucosa of stomach	UBERON:0001199	82.87	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.33	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	82.24	gold quality
lower esophagus	UBERON:0013473	82.17	gold quality
thoracic mammary gland	UBERON:0005200	81.12	gold quality
omental fat pad	UBERON:0010414	80.95	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.87	gold quality
gastrocnemius	UBERON:0001388	80.71	gold quality
muscle of leg	UBERON:0001383	80.37	gold quality
tibial nerve	UBERON:0001323	79.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.17	gold quality
skeletal muscle tissue	UBERON:0001134	78.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.41	gold quality
muscle layer of sigmoid colon	UBERON:0035805	76.88	gold quality
sigmoid colon	UBERON:0001159	76.75	gold quality
esophagus	UBERON:0001043	74.96	gold quality
heart	UBERON:0000948	74.32	gold quality
muscle tissue	UBERON:0002385	73.93	gold quality
colonic epithelium	UBERON:0000397	73.90	gold quality
colon	UBERON:0001155	73.51	gold quality
calcaneal tendon	UBERON:0003701	73.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CLOCK, CREB1, CTNNB1, EGR1, FLI1, FOXA2, FOXE1, GABPA, HIF1A, HNF4A, IRF6, NFIA, NFIC, NKX2-1, NKX2-5, NR4A1, PAX8, RARA, RUNX1, TCF7, TP53, TTF1, TTF2, USF1, USF2

miRNA regulators (miRDB)

19 targeting TPO, 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-4425	100.00	67.59	1049
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-6811-3P	98.62	66.54	944
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-6514-3P	97.52	66.50	808
HSA-MIR-370-3P	97.09	64.92	1221
HSA-MIR-6872-3P	97.08	66.99	750
HSA-MIR-28-3P	96.42	67.18	579
HSA-MIR-433-5P	94.67	64.82	99

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Two novel missense mutations in the thyroid peroxidase gene, R665W and G771R, result in a localization defect and cause congenital hypothyroidism. (PMID:11916616)
• Thyroperoxidase folds in one complex B-cell immunodominant region. (PMID:12135610)
• High prevalence of a novel mutation pf the High prevalence of a novel mutation (2268 insT) of the thyroid peroxidase gene in Taiwanese patients with total iodide organification defect, and evidence for a founder effect (PMID:12213873)
• investigation of diversity generated by alternative splicing (PMID:12454013)
• Positivity in TPO-RT-PCR correlates significantly with metastatic disease in cancer patients and with the presence of thyroid disease in general. (PMID:12459031)
• human TPO has a discontinuous immunodominant region recognized by human anti-thyroperoxidase autoantibodies in autoimmune thyroid diseases (PMID:12501244)
• the location of the TPO immunodominant region is, from their binding characteristics, the CCP/EGF-like domain lies on the fringe of the TPO immunodominant region. (PMID:12593722)
• This enzyme is a marker in thyroid tumors. (PMID:12820316)
• The distribution of the polymorphisms indicated that only the mutant paternal allele is transcribed at the thyroid tissue level so this mechanism might be generally involved in total iodide organificaton defect cases with a single TPO-mutated allele. (PMID:12843174)
• Five novel inactivating mutations in the TPO gene have been identified in patients with congenital goiter and iodide organification defects. (PMID:12938097)
• C4 may bind to TPO and activate the complement pathway in autoimmune conditions. (PMID:12960013)
• TPO gene sequence alterations may partially affect the functional state of the translated protein or affect its transport to the apical membrane. (PMID:14751036)
• organification of radioiodide into proteins of thyroid cancer cells exogenously co-expressing TPO and the sodium/iodide symporter (NIS) is strictly dependent of TPO and not of NIS. (PMID:15062578)
• identification of the minimal epitope 713-717 recognized by mAb 47 (a reference antibody) and the amino acids used as contact points for two IDR-specific human monoclonal autoantibodies (PMID:15150267)
• In conclusion, the results of this study show that the splicing of hTPO increases in benign and malignant thyroid tissues. (PMID:15196594)
• The autoimmune response to TPO regions outside the IDR (A + B) epitopes is stronger then previously assumed and this response is also conformation dependent. (PMID:15497454)
• Hypothyroidism during type I interferon therapy may be related to an abnormal expression and function of key proteins involved in iodine uptake and organification. (PMID:15562032)
• the prosequence of thyroperoxidase plays a crucial role as an intramolecular chaperone, facilitating the folding of hTPO (PMID:15590661)
• results are in accordance with previous observations confirming the genetic heterogeneity of TPO defects in congenital hypothyroidism (PMID:15745925)
• residues (604)ETP-DL(609) play a role in the anti-peptide P14 epitope and that IDR/A-specific human anti-TPO aAbs, expressed as recombinant Fab or obtained from Graves’ disease patients, recognize the sequences (597)FCGLPRLE(604) and (611)TAIASRSV(618) (PMID:15761037)
• In conclusion, incubation of normal or GD thyrocytes with Th1 cytokines induces a significant reduction in TSH-increased expression of both TPO and ThOXs, an effect partially mediated by NO. (PMID:16478776)
• Immunohistochemical assay of TPO expression has limited value for the differential diagnosis of follicular thyroid carcinoma from thyroid follicular adenoma. (PMID:16614712)
• thyroid peroxidase may have a role in development of thyroid papillary carcinoma (PMID:16756464)
• presence of TPO in Graves’ ophthalmopathy and normal orbital adipose tissues (PMID:16868133)
• Identification of key residues within the autoreactive epitopes of TPO. (PMID:16959834)
• Evolution of thyroid peroxidase antibody (TPOAb) and thyrtropin receptor antibody activities before, during, and after treatment of Graves’ disease (GD) with carbimazole. (PMID:17042691)
• a subgroup of type 1 diabetic patients has a female bias, a failure in tolerance to thyroid peroxidase, and is sensitive to allelic variation of the negative regulatory molecule CTLA-4 (PMID:17334650)
• Three different TPO gene mutations were found to be responsible for iodide organification defect in a consanguineous Israeli population. (PMID:17381485)
• results showed a higher prevalence of TPO gene mutations in thyroid dyshormonogenesis when compared with published studies; the high percentage of single allele mutations implied possible intronic or regulatory TPO gene mutations or monoallelic expression (PMID:17468186)
• Two compound heterozygous mutations (c.215delA/c.2422T–>C and c.387delC/c.1159G–>A) in the thyroid peroxidase gene are responsible for congenital goitre and iodide organification defect.(238-46) (PMID:17547680)
• Significant reduction of serum anti-TPO levels during the first 6 months of selenomethionine therapy in Hashimoto thyroiditis. (PMID:17696828)
• TPO antibodies could be used as a screening test for postpartum thyroid dysfunction (PPTD) prediction at least among women who present a high risk of developing PPTD. (PMID:17845204)
• Papillary thyroid cancers Papillary thyroid cancers with no 131I uptake had slightly reduced NIS, significantly reduced thyroglobulin,thyroperoxidase and pendrin and significantly increased GLUT-1 gene expression levels. (PMID:17854396)
• There is no systematic variation during the menstrual cycle in autoantibodies against thyroid peroxidase, thyroglobulin, and thyrotropin receptor (PMID:17902201)
• Although goitrous congenital hypothyroidism generally follows a recessive mode of inheritance, the high frequency of TPO mutations carriers may lead to pseudodominant inheritance. (PMID:18029453)
• connection between infection of H. pylori and the occurrence of anti-TPO autoantibodies representing thyroid autoimmunity and gastric parietal cells autoantibodies representing the thyrogastric syndrome (PMID:18271683)
• study revealed a significant correlation of BRAFV600E mutation with a lower expression of both sodium iodide symporter and thyroperoxidase in papillary thyroid cancer (PMID:18509003)
• there is as yet no conclusive kinetic evidence that iodination occurs via formation of a TPO-bound iodinated intermediate (PMID:18631006)
• Although thyroperoxidase presence may indicate favorable prognosis of papillary cancer, expression of galectin-3 illustrates the potential importance of this protein in the pathogenesis and/or progression of differentiated thyroid carcinomas. (PMID:18657294)
• The finding of higher PDS, TPO and TSH-R mRNA expression in paediatric vs. adult primary tumour tissues supports the hypothesis that this might contribute to the increased functional activity of metastases in the paediatric group. (PMID:18710471)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tpo	ENSMUSG00000020673
rattus_norvegicus	Tpo	ENSRNOG00000004646
drosophila_melanogaster	Pxd	FBGN0004577
drosophila_melanogaster	CG4009	FBGN0038469

Paralogs (5): MPO (ENSG00000005381), EPX (ENSG00000121053), PXDN (ENSG00000130508), PXDNL (ENSG00000147485), LPO (ENSG00000167419)

Protein

Protein identifiers

Thyroid peroxidase — P07202 (reviewed: P07202)

All UniProt accessions (6): P07202, C9J511, E9PFM6, H0Y6H4, H7C1F5, H7C5B6

UniProt curated annotations — full annotation on UniProt →

Function. Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4).

Subunit / interactions. Interacts with DUOX1, DUOX2 and CYBA.

Subcellular location. Membrane Cell surface.

Post-translational modifications. Glycosylated. Heme is covalently bound through a H(2)O(2)-dependent autocatalytic process. Heme insertion is important for the delivery of protein at the cell surface. Cleaved in its N-terminal part.

Disease relevance. An alternative splicing in the thyroperoxidase mRNA can cause Graves’ disease. Thyroid dyshormonogenesis 2A (TDH2A) [MIM:274500] A disorder due to defective conversion of accumulated iodide to organically bound iodine. The iodide organification defect can be partial or complete. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 Ca(2+) ion per heterodimer. Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per heterodimer.

Pathway. Hormone biosynthesis; thyroid hormone biosynthesis.

Miscellaneous. Lacks exon 10. Found in normal thyroid tissues as well as Graves’tissues. Rapidly degraded after synthesis, does not reach the cell surface. Inactive. Lacks exon 16. Found in normal thyroid tissues as well as Graves’tissues. Active. Lacks exon 14. Active. Lacks exon 8. Does not fold correctly. Does not reach the cell surface. Lacks exons 10, 12, 13, 14 and 16. Lacks exons 10 and 16. Lacks exons 10 and 14.

Similarity. Belongs to the peroxidase family. XPO subfamily.

Isoforms (8)

UniProt ID	Names	Canonical?
P07202-1	1, TPO1	yes
P07202-2	2, TPO2
P07202-3	3, TPO3, Graves’ disease, TPOzaninelli
P07202-4	4, TPO4
P07202-5	5, TPO5
P07202-6	6, TPO6
P07202-7	2-3
P07202-8	2-4

RefSeq proteins (6): NP_000538, NP_001193673, NP_001193674, NP_783650, NP_783652, NP_783653 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR010255	Haem_peroxidase_sf	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR019791	Haem_peroxidase_animal	Family
IPR029589	TPO	Family
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily
IPR037120	Haem_peroxidase_sf_animal	Homologous_superfamily
IPR049883	NOTCH1_EGF-like	Domain

Pfam: PF00084, PF03098, PF07645

Enzyme classification (BRENDA):

• EC 1.11.1.8 — iodide peroxidase (BRENDA: 7 organisms, 28 substrates, 77 inhibitors, 13 Km, 6 kcat entries)
• EC 3.6.1.52 — diphosphoinositol-polyphosphate diphosphatase (BRENDA: 7 organisms, 75 substrates, 14 inhibitors, 14 Km, 20 kcat entries)

Substrate kinetics (BRENDA)

22 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DIPHOSPHOINOSITOL PENTAKISPHOSPHATE	—	6
GUAIACOL	5.55–9.67	4
I-	0.18–7.7	3
3,3’,5,5’-TETRAMETHYLBENZIDINE	0.166	1
3,3’-DIMETHOXYBENZIDINE	0.058	1
3,3’-DIMETHYLBENZIDINE	0.177	1
BENZIDINE	0.049	1
BR-	22	1
H2O2	0.034	1
4-NITROPHENYL PHOSPHATE	3	1
5-DIPHOSPHOINOSITOL PENTAKISPHOSPHATE	0.035	1
5-PHOSPHO-D-RIBOSYL 1-DIPHOSPHATE	0.13	1
ADENOSINE TETRAPHOSPHATE	0.004	1
BISDIPHOSPHOINOSITOL TETRAKISPHOSPHATE	—	1
DIADENOSINE 5’,5’’’-P1,P6-HEXAPHOSPHATE	0.018	1

Catalyzed reactions (Rhea), 5 shown:

• 2 iodide + H2O2 + 2 H(+) = diiodine + 2 H2O (RHEA:23336)
• [thyroglobulin]-L-tyrosine + iodide + H2O2 + H(+) = [thyroglobulin]-3-iodo-L-tyrosine + 2 H2O (RHEA:48956)
• [thyroglobulin]-3-iodo-L-tyrosine + iodide + H2O2 + H(+) = [thyroglobulin]-3,5-diiodo-L-tyrosine + 2 H2O (RHEA:48960)
• 2 [thyroglobulin]-3,5-diiodo-L-tyrosine + H2O2 = [thyroglobulin]-L-thyroxine + [thyroglobulin]-dehydroalanine + 2 H2O (RHEA:48964)
• [thyroglobulin]-3-iodo-L-tyrosine + [thyroglobulin]-3,5-diiodo-L-tyrosine + H2O2 = [thyroglobulin]-3,3’,5-triiodo-L-thyronine + [thyroglobulin]-dehydroalanine + 2 H2O (RHEA:48968)

UniProt features (81 total): sequence variant 36, sequence conflict 9, binding site 8, disulfide bond 8, splice variant 5, glycosylation site 4, topological domain 2, domain 2, signal peptide 1, chain 1, site 1, transmembrane region 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07202-F1	84.00	0.57

Functional residue map

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

Catalytic / active sites (2): 396 (transition state stabilizer); 239 (proton acceptor)

Ligand- & substrate-binding residues (8): 238 (covalent); 240; 321; 323; 325; 327; 399 (covalent); 494 (axial binding residue)

Disulfide bonds (8): 142–158, 259–269, 263–286, 598–655, 696–721, 800–814, 808–823, 825–838

Glycosylation sites (4): 129, 307, 342, 569

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-209968	Thyroxine biosynthesis

MSigDB gene sets: 182 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_EMBRYONIC_HEMOPOIESIS, chr2p25, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_HYDROGEN_PEROXIDE_CATABOLIC_PROCESS, MODULE_64, GOBP_REGULATION_OF_HORMONE_LEVELS, GOCC_CELL_SURFACE, GOBP_THYROID_HORMONE_METABOLIC_PROCESS, MARTINEZ_RB1_TARGETS_UP, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, KLEIN_PRIMARY_EFFUSION_LYMPHOMA_UP, KEGG_AUTOIMMUNE_THYROID_DISEASE, DELYS_THYROID_CANCER_DN, GOBP_HORMONE_BIOSYNTHETIC_PROCESS

GO Biological Process (6): thyroid hormone generation (GO:0006590), response to oxidative stress (GO:0006979), embryonic hemopoiesis (GO:0035162), hormone biosynthetic process (GO:0042446), hydrogen peroxide catabolic process (GO:0042744), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (6): iodide peroxidase activity (GO:0004447), peroxidase activity (GO:0004601), calcium ion binding (GO:0005509), heme binding (GO:0020037), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

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	2
thyroid hormone metabolic process	1
response to stress	1
hemopoiesis	1
embryonic organ development	1
biosynthetic process	1
hormone metabolic process	1
catabolic process	1
hydrogen peroxide metabolic process	1
cellular detoxification	1
haloperoxidase activity	1
antioxidant activity	1
oxidoreductase activity, acting on peroxide as acceptor	1
metal ion binding	1
tetrapyrrole binding	1
catalytic activity	1
cation binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1074 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPO	TG	P01266	986
TPO	TSHR	P16473	969
TPO	SLC5A5	Q92911	934
TPO	TBL1X	O60907	914
TPO	SLC26A4	O43511	861
TPO	IYD	Q6PHW0	847
TPO	DUOXA2	Q1HG44	770
TPO	PAX8	Q06710	730
TPO	FOXE1	O00358	710
TPO	NKX2-1	P43699	687
TPO	H7C2H4	H7C2H4	667
TPO	P0DN79	P0DN79	667
TPO	CTLA4	P16410	643
TPO	ATP5PO	P48047	611
TPO	Q5Y7H0	Q5Y7H0	604

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1Y9G8H0, A0A452E9Y6, A5JUY8, A8WQH2, B3A0Q8, F9FAJ9, G4N2X9, G4N4J5, G5EG78, H2A0M7, O02768, O19183, O61213, O62664, O62698, O62725, O97554, P05979, P07202, P09933, P14650, P22079, P22437, P23219, P27607, P29812, P35354, P35355, P35419, P70682, P79208, P80025, P82600, P90820, Q01603, Q05769, Q1ENI8, Q20616, Q23490, Q4WY82

Diamond homologs: A0A1D5NSM8, A0JNA2, A2AVA0, A2AX52, D3YXF5, O02839, O19063, O35764, O43405, O70340, O76536, O89029, O95502, O96530, P02741, P02743, P06205, P06206, P06207, P06681, P07202, P07629, P08607, P09871, P0C6B8, P10643, P12246, P13944, P14151, P14847, P15697, P18337, P23680, P32018, P47970, P47971, P47972, P48199, P49254, P49262

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
TPO	“up-regulates activity”	TG	“catalytic activity”
TPO	“down-regulates quantity”	“L-tyrosine zwitterion”	“chemical modification”
TPO	“up-regulates quantity”	3-iodo-L-tyrosine	“chemical modification”
TPO	“up-regulates quantity”	diiodine	“chemical modification”
TPO	“up-regulates quantity”	3,5-diiodo-L-tyrosine	“chemical modification”
TPO	“up-regulates quantity”	3,3’,5’-triiodothyronine	“chemical modification”
TPO	“up-regulates quantity”	L-thyroxine	“chemical modification”
TPO	“up-regulates quantity”	“L-alanine zwitterion”	“chemical modification”
PAX8	“up-regulates quantity by expression”	TPO	“transcriptional regulation”
NKX2-1	“up-regulates quantity by expression”	TPO	“transcriptional regulation”
FOXE1	“up-regulates quantity by expression”	TPO	“transcriptional regulation”
iodide	“up-regulates activity”	TPO	“chemical activation”
“bisphenol A”	“down-regulates activity”	TPO	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	43
Likely pathogenic	37
Uncertain significance	98
Likely benign	246
Benign	35

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1028337	NM_001206744.2(TPO):c.214C>T (p.Gln72Ter)	Pathogenic
1064772	NM_001206744.2(TPO):c.1477G>A (p.Gly493Ser)	Pathogenic
1323705	NM_001206744.2(TPO):c.31_50dup (p.Glu17fs)	Pathogenic
1701830	NM_001206744.2(TPO):c.265C>T (p.Arg89Ter)	Pathogenic
2581320	NM_001206744.2(TPO):c.2492T>G (p.Leu831Ter)	Pathogenic
2695050	NM_001206744.2(TPO):c.769del (p.Ala257fs)	Pathogenic
2701862	NM_001206744.2(TPO):c.681del (p.Asp228fs)	Pathogenic
2734125	NM_001206744.2(TPO):c.523C>T (p.Arg175Ter)	Pathogenic
2734128	NM_001206744.2(TPO):c.1581G>T (p.Trp527Cys)	Pathogenic
2734130	NM_001206744.2(TPO):c.1993C>T (p.Arg665Trp)	Pathogenic
2765529	NM_001206744.2(TPO):c.1072_1079dup (p.Arg361fs)	Pathogenic
2770499	NM_001206744.2(TPO):c.295C>T (p.Gln99Ter)	Pathogenic
2795477	NM_001206744.2(TPO):c.1525C>T (p.Gln509Ter)	Pathogenic
2803538	NM_001206744.2(TPO):c.1365del (p.Arg456fs)	Pathogenic
2806730	NM_001206744.2(TPO):c.1586T>G (p.Leu529Ter)	Pathogenic
2815017	NM_001206744.2(TPO):c.1282dup (p.Trp428fs)	Pathogenic
2817149	NM_001206744.2(TPO):c.450del (p.Lys150fs)	Pathogenic
2852236	NM_001206744.2(TPO):c.597del (p.Phe200fs)	Pathogenic
2856954	NM_001206744.2(TPO):c.1132_1135dup (p.Pro379fs)	Pathogenic
2910135	NM_001206744.2(TPO):c.666TGA[1] (p.Asp224del)	Pathogenic
2967093	NM_001206744.2(TPO):c.565C>T (p.Arg189Ter)	Pathogenic
2970290	NM_001206744.2(TPO):c.1270del (p.Leu424fs)	Pathogenic
2978824	NM_001206744.2(TPO):c.779_780insTCTA (p.Gln260fs)	Pathogenic
2989633	NM_001206744.2(TPO):c.778C>T (p.Gln260Ter)	Pathogenic
3247465	NC_000002.11:g.(?1418181)(1546310_?)del	Pathogenic
3247466	NC_000002.11:g.(?1418181)(1418294_?)del	Pathogenic
3247467	NC_000002.11:g.(?1499741)(1500557_?)del	Pathogenic
3584382	NM_001206744.2(TPO):c.796C>T (p.Gln266Ter)	Pathogenic
3584385	NM_001206744.2(TPO):c.1336del (p.Gln446fs)	Pathogenic
3641172	NM_001206744.2(TPO):c.650del (p.Asn217fs)	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

6064 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:1487974:G:C	R584P	0.996
2:1487976:G:C	D585H	0.993
2:1487960:C:A	N579K	0.992
2:1487960:C:G	N579K	0.992
2:1493813:T:A	W594R	0.992
2:1493813:T:C	W594R	0.992
2:1487962:T:C	L580P	0.990
2:1493936:T:A	W635R	0.990
2:1493936:T:C	W635R	0.990
2:1456160:T:A	W233R	0.989
2:1456160:T:C	W233R	0.989
2:1487982:G:T	G587W	0.988
2:1484723:C:A	A489D	0.987
2:1487947:T:C	L575P	0.987
2:1487973:C:G	R584G	0.987
2:1504001:T:A	C814S	0.987
2:1504002:G:C	C814S	0.987
2:1487970:G:C	G583R	0.986
2:1487977:A:C	D585A	0.986
2:1504028:T:A	C823S	0.986
2:1504029:G:C	C823S	0.986
2:1456238:T:A	C259S	0.984
2:1456239:G:C	C259S	0.984
2:1477152:T:A	C296S	0.984
2:1477153:G:C	C296S	0.984
2:1487983:G:A	G587E	0.984
2:1487969:G:C	R582S	0.983
2:1487969:G:T	R582S	0.983
2:1487977:A:T	D585V	0.983
2:1436374:T:A	C158S	0.982

dbSNP variants (sampled 300 via entrez): RS1000002093 (2:1397879 C>T), RS1000023957 (2:1439127 C>T), RS1000077669 (2:1438862 G>C), RS1000099380 (2:1416338 C>A), RS1000111673 (2:1429024 A>T), RS1000130810 (2:1508676 G>A), RS1000131660 (2:1446652 T>G), RS1000135514 (2:1479098 C>T), RS1000141650 (2:1474650 G>A,C), RS1000166307 (2:1516555 C>G), RS1000167228 (2:1482729 C>T), RS1000188141 (2:1452243 G>C), RS1000201121 (2:1448069 C>G), RS1000230097 (2:1374206 C>A,T), RS1000235603 (2:1522549 A>G)

Disease associations

OMIM: gene MIM:606765 | disease phenotypes: MIM:274500, MIM:275200

GenCC curated gene-disease

Disease	Classification	Inheritance
thyroid dyshormonogenesis 2A	Strong	Autosomal recessive
familial thyroid dyshormonogenesis	Supportive	Autosomal recessive

Mondo (5): thyroid dyshormonogenesis 2A (MONDO:0010133), neurodevelopmental disorder (MONDO:0700092), congenital hypothyroidism (MONDO:0018612), hypothyroidism due to TSH receptor mutations (MONDO:0010142), familial thyroid dyshormonogenesis (MONDO:0010132)

Orphanet (3): Familial thyroid dyshormonogenesis (Orphanet:95716), Congenital hypothyroidism (Orphanet:442), Hypothyroidism due to TSH receptor mutations (Orphanet:90673)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002373_1	Thyroid peroxidase antibody levels	7.000000e-13
GCST002378_1	Thyroid peroxidase antibody positivity	2.000000e-16
GCST002416_1	Thyroid peroxidase antibody positivity	1.000000e-10
GCST003988_13	Hypothyroidism	6.000000e-14
GCST004739_2	Placebo response in major depressive disorder (% change in symptom score)	3.000000e-06
GCST005412_4	Thrombin-activatable fibrinolysis inhibitor levels	5.000000e-07
GCST006898_3	Hypothyroidism	2.000000e-10
GCST007932_72	Medication use (thyroid preparations)	6.000000e-25
GCST010571_82	Autoimmune thyroid disease	1.000000e-21
GCST010653_61	Thyroid stimulating hormone levels	1.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008344	response to placebo
EFO:0009933	Thyroid preparation use measurement

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
D065886	Neurodevelopmental Disorders	F03.625
C564766	Thyroid Dyshormonogenesis 1 (supp.)
C563206	Thyroid Dyshormonogenesis 2A (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1839 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 15,134 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1518	PROPYLTHIOURACIL	4	15,046
CHEMBL5095218	MITIPERSTAT	2	52
CHEMBL3633460	PF-06282999	1	36

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Thyroid hormone turnover

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
mitiperstat	Inhibition	6.16	pIC50

Binding affinities (BindingDB)

15 measured of 15 human assays (19 total across all organisms); most potent 15 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(1-Aminoethyl)-4-chlorobenzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one	IC50	7 nM	US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase
Alternative Preparation	IC50	7 nM	US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase
1-{2-[(1R)-1-Aminopropyl]-4-chlorobenzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one	IC50	8.6 nM	US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase
1-{2-[(Cyclobutylamino)methyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one	IC50	10 nM	US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase
1-{4-Chloro-2-[(methylamino)methyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one	IC50	13 nM	US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase
1-{2-[(Cyclopentylamino)methyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one	IC50	14 nM	US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase
1-[2-(Aminomethyl)-4-chlorobenzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one	IC50	15 nM	US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase
1-{4-Chloro-2-[1-(methylamino)ethyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one	IC50	19 nM	US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase
1-{4-Chloro-2-[(ethylamino)methyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one	IC50	22 nM	US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase
1-{2-[(Propan-2-ylamino)methyl]benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one	IC50	24 nM	US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase
1-(2-{[(Cyclobutylmethyl)amino]methyl}benzyl)-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one	IC50	29 nM	US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase
1-[2-(Aminomethyl)-4-(trifluoromethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one	IC50	40 nM	US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase
1-{2-[(1S)-1-Aminoethyl]-4-chlorobenzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one	IC50	42 nM	US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase
1-{2-[(Methylamino)methyl]-4-(trifluoromethyl)benzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one	IC50	49 nM	US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase
1-(2-{[(2-Methylpropyl)amino]methyl}benzyl)-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one	IC50	54 nM	US-10016430: 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase

ChEMBL bioactivities

52 potent at pChembl≥5 of 88 total, top 42 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.23	IC50	590	nM	CHEMBL5200638
6.19	IC50	640	nM	CHEMBL4859908
6.16	IC50	700	nM	CHEMBL4869433
6.15	IC50	710	nM	CHEMBL4855931
6.11	IC50	770	nM	CHEMBL5181350
6.05	IC50	890	nM	MITIPERSTAT
6.00	IC50	990	nM	PF-06282999
5.96	IC50	1100	nM	CHEMBL4853722
5.96	IC50	1100	nM	CHEMBL4863015
5.96	IC50	1100	nM	CHEMBL4862053
5.96	IC50	1100	nM	CHEMBL5200126
5.96	IC50	1100	nM	CHEMBL5200597
5.89	IC50	1300	nM	CHEMBL5172456
5.86	IC50	1390	nM	CHEMBL5197968
5.85	IC50	1400	nM	CHEMBL5175091
5.82	IC50	1500	nM	CHEMBL5185576
5.77	IC50	1700	nM	CHEMBL4860429
5.75	IC50	1800	nM	CHEMBL4871587
5.72	IC50	1900	nM	CHEMBL4878518
5.72	IC50	1900	nM	CHEMBL5186129
5.70	IC50	2000	nM	CHEMBL4855030
5.68	IC50	2100	nM	CHEMBL5205410
5.66	IC50	2200	nM	CHEMBL4753981
5.64	IC50	2300	nM	CHEMBL4846080
5.62	IC50	2400	nM	CHEMBL4278946
5.47	IC50	3380	nM	PROPYLTHIOURACIL
5.47	IC50	3400	nM	CHEMBL5197383
5.41	IC50	3900	nM	CHEMBL4278946
5.40	IC50	4000	nM	CHEMBL4482878
5.38	IC50	4200	nM	CHEMBL5181827
5.38	IC50	4200	nM	CHEMBL5207346
5.37	IC50	4300	nM	MITIPERSTAT
5.36	IC50	4400	nM	CHEMBL5897801
5.28	IC50	5300	nM	CHEMBL4645343
5.23	IC50	5900	nM	CHEMBL4633000
5.22	IC50	6000	nM	CHEMBL4282403
5.20	IC50	6300	nM	CHEMBL4792720
5.17	IC50	6700	nM	CHEMBL4855956
5.09	IC50	8100	nM	CHEMBL5182747
5.06	IC50	8800	nM	CHEMBL5936050
5.05	IC50	8900	nM	CHEMBL5883027
5.00	IC50	1e+04	nM	CHEMBL5763445

PubChem BioAssay actives

41 with measured affinity, of 68 total; 40 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-benzyl-N,2-dihydroxybenzamide	1802479: LPO/TPO Selectivity Assay from Article 10.1074/jbc.M113.507756: “Potent reversible inhibition of myeloperoxidase by aromatic hydroxamates.”	ic50	0.0630	uM
3-[(4-fluorophenyl)methyl]-2-sulfanylidene-7H-purin-6-one	1875008: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay	ic50	0.5900	uM
7-[(1-phenylpyrazol-3-yl)methyl]-2H-triazolo[4,5-b]pyridin-5-amine	1753666: Inhibition of C-terminal hexaHis-tagged TPO (unknown origin) expressed in Trichoplusia ni insect cells using 3-iodo tyrosine as substrate preincubated for 10 mins followed by substrate and H2O2 addition and further incubated for 15 mins	ic50	0.6400	uM
7-[[1-(4-fluorophenyl)pyrazol-3-yl]methyl]-2H-triazolo[4,5-b]pyridin-5-amine	1753666: Inhibition of C-terminal hexaHis-tagged TPO (unknown origin) expressed in Trichoplusia ni insect cells using 3-iodo tyrosine as substrate preincubated for 10 mins followed by substrate and H2O2 addition and further incubated for 15 mins	ic50	0.7000	uM
7-[[1-(3-phenylphenyl)pyrazol-3-yl]methyl]-2H-triazolo[4,5-b]pyridin-5-amine	1753666: Inhibition of C-terminal hexaHis-tagged TPO (unknown origin) expressed in Trichoplusia ni insect cells using 3-iodo tyrosine as substrate preincubated for 10 mins followed by substrate and H2O2 addition and further incubated for 15 mins	ic50	0.7100	uM
3-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-7H-purin-6-one	1875008: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay	ic50	0.7700	uM
1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one	1875008: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay	ic50	0.8900	uM
2-[6-(5-chloro-2-methoxyphenyl)-4-oxo-2-sulfanylidenepyrimidin-1-yl]acetamide	1875008: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay	ic50	0.9900	uM
1-[[2-[(1S)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one	1875008: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay	ic50	1.1000	uM
7-[[1-(naphthalen-2-ylmethyl)pyrazol-3-yl]methyl]-2H-triazolo[4,5-b]pyridin-5-amine	1753666: Inhibition of C-terminal hexaHis-tagged TPO (unknown origin) expressed in Trichoplusia ni insect cells using 3-iodo tyrosine as substrate preincubated for 10 mins followed by substrate and H2O2 addition and further incubated for 15 mins	ic50	1.1000	uM
7-[[1-[(3-phenylphenyl)methyl]pyrazol-3-yl]methyl]-2H-triazolo[4,5-b]pyridin-5-amine	1753666: Inhibition of C-terminal hexaHis-tagged TPO (unknown origin) expressed in Trichoplusia ni insect cells using 3-iodo tyrosine as substrate preincubated for 10 mins followed by substrate and H2O2 addition and further incubated for 15 mins	ic50	1.1000	uM
7-[[1-[(3-phenoxyphenyl)methyl]pyrazol-3-yl]methyl]-2H-triazolo[4,5-b]pyridin-5-amine	1753666: Inhibition of C-terminal hexaHis-tagged TPO (unknown origin) expressed in Trichoplusia ni insect cells using 3-iodo tyrosine as substrate preincubated for 10 mins followed by substrate and H2O2 addition and further incubated for 15 mins	ic50	1.1000	uM
1-[[4-chloro-2-[(1R)-1-(methylamino)ethyl]phenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one	1875008: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay	ic50	1.1000	uM
1-[[2-(aminomethyl)-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one	1875008: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay	ic50	1.3000	uM
1-[[2-[amino(phenyl)methyl]phenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one	1875008: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay	ic50	1.3900	uM
N-[[5-chloro-2-[(4-oxo-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-1-yl)methyl]phenyl]methyl]acetamide	1875008: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay	ic50	1.4000	uM
1-[[2-(azetidin-1-ylmethyl)phenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one	1875008: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay	ic50	1.5000	uM
2-[[3,5-bis(trifluoromethyl)phenyl]methylamino]-N-hydroxy-4-oxo-1,3-diazinane-5-carboxamide	1802479: LPO/TPO Selectivity Assay from Article 10.1074/jbc.M113.507756: “Potent reversible inhibition of myeloperoxidase by aromatic hydroxamates.”	ic50	1.5900	uM
2-(benzylamino)-N-hydroxy-4-oxo-1,3-diazinane-5-carboxamide	1802479: LPO/TPO Selectivity Assay from Article 10.1074/jbc.M113.507756: “Potent reversible inhibition of myeloperoxidase by aromatic hydroxamates.”	ic50	1.5900	uM
7-[[1-[[3-(2,3-dihydro-1H-isoindol-4-yloxy)phenyl]methyl]pyrazol-3-yl]methyl]-2H-triazolo[4,5-b]pyridin-5-amine	1753666: Inhibition of C-terminal hexaHis-tagged TPO (unknown origin) expressed in Trichoplusia ni insect cells using 3-iodo tyrosine as substrate preincubated for 10 mins followed by substrate and H2O2 addition and further incubated for 15 mins	ic50	1.7000	uM
7-[[1-(isoquinolin-6-ylmethyl)pyrazol-3-yl]methyl]-2H-triazolo[4,5-b]pyridin-5-amine	1753666: Inhibition of C-terminal hexaHis-tagged TPO (unknown origin) expressed in Trichoplusia ni insect cells using 3-iodo tyrosine as substrate preincubated for 10 mins followed by substrate and H2O2 addition and further incubated for 15 mins	ic50	1.8000	uM
7-[[1-[(3-benzylphenyl)methyl]pyrazol-3-yl]methyl]-2H-triazolo[4,5-b]pyridin-5-amine	1753666: Inhibition of C-terminal hexaHis-tagged TPO (unknown origin) expressed in Trichoplusia ni insect cells using 3-iodo tyrosine as substrate preincubated for 10 mins followed by substrate and H2O2 addition and further incubated for 15 mins	ic50	1.9000	uM
1-[[5-chloro-2-(methylaminomethyl)phenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one	1875008: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay	ic50	1.9000	uM
7-[(1-pyridin-2-ylpyrazol-3-yl)methyl]-2H-triazolo[4,5-b]pyridin-5-amine	1753666: Inhibition of C-terminal hexaHis-tagged TPO (unknown origin) expressed in Trichoplusia ni insect cells using 3-iodo tyrosine as substrate preincubated for 10 mins followed by substrate and H2O2 addition and further incubated for 15 mins	ic50	2.0000	uM
N,2-dihydroxybenzamide	1802479: LPO/TPO Selectivity Assay from Article 10.1074/jbc.M113.507756: “Potent reversible inhibition of myeloperoxidase by aromatic hydroxamates.”	ic50	2.0000	uM
1-[[4-chloro-2-(methylaminomethyl)phenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one	1875008: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay	ic50	2.1000	uM
7-benzyl-2H-triazolo[4,5-b]pyridin-5-amine	1698299: Inhibition of TPO (unknown origin) using 3-iodo tyrosine as substrate incubated for 10 mins	ic50	2.2000	uM
7-[(1-benzylpyrazol-3-yl)methyl]-2H-triazolo[4,5-b]pyridin-5-amine	1753666: Inhibition of C-terminal hexaHis-tagged TPO (unknown origin) expressed in Trichoplusia ni insect cells using 3-iodo tyrosine as substrate preincubated for 10 mins followed by substrate and H2O2 addition and further incubated for 15 mins	ic50	2.3000	uM
3-[[(2R)-oxolan-2-yl]methyl]-2-sulfanylidene-7H-purin-6-one	1875008: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay	ic50	2.4000	uM
Propylthiouracil	1256929: Inhibition of TPO (unknown origin) using Amplex Red as substrate assessed as formation of resorufin measured every 20 secs by spectrophotometric analysis	ic50	3.3800	uM
1-[[4-chloro-2-[(2,2-dimethylpropylamino)methyl]phenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one	1875008: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay	ic50	3.4000	uM
7-[(2-fluorophenyl)methylsulfanyl]-2H-triazolo[4,5-b]pyridin-5-amine	1533025: Inhibition of human TPO assessed as reduction in H2O2 catalyzed 3,5-iodo tyrosine formation from 3-iodotyrosine and potassium iodide preincubated for 10 mins followed by tyrosine/potassium bromide/H2O2 addition measured after 15 mins	ic50	4.0000	uM
3-[[2-[(propan-2-ylamino)methyl]phenyl]methyl]-2-sulfanylidene-7H-purin-6-one	1875008: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay	ic50	4.2000	uM
1-[[3-chloro-2-(methylaminomethyl)phenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one	1875008: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay	ic50	4.2000	uM
1-[4-[4-chloro-3-(1H-indol-6-yl)pyrrolo[2,3-b]pyridin-1-yl]phenyl]-N,N-dimethylmethanamine	1663378: Inhibition of thyroid peroxidase (unknown origin)	ic50	5.3000	uM
6-[1-[4-(1H-1,2,4-triazol-5-ylmethyl)phenyl]-3-(trifluoromethyl)pyrazol-4-yl]-1H-indole	1663378: Inhibition of thyroid peroxidase (unknown origin)	ic50	5.9000	uM
5-(2,4,5-trichlorophenoxy)pyridin-2-amine	1416584: Inhibition of recombinant human C-terminal His6-tagged TPO (15 to 839 residues) expressed in baculovirus infected insect cells assessed as reduction in H2O2-catalyzed 3,5-iodo tyrosine formation using 3-iodotyrosine and potassium iodide preincubated for 10 mins followed by 3,5-iodo tyrosine/potassium iodide/H2O2 addition and measured after 15 mins	ic50	6.0000	uM
7-[(1R)-1-phenyl-3-phenylmethoxypropyl]-2H-triazolo[4,5-b]pyridin-5-amine	1698299: Inhibition of TPO (unknown origin) using 3-iodo tyrosine as substrate incubated for 10 mins	ic50	6.3000	uM
7-[[1-(1,2,3,4-tetrahydroisoquinolin-6-ylmethyl)pyrazol-3-yl]methyl]-2H-triazolo[4,5-b]pyridin-5-amine	1753666: Inhibition of C-terminal hexaHis-tagged TPO (unknown origin) expressed in Trichoplusia ni insect cells using 3-iodo tyrosine as substrate preincubated for 10 mins followed by substrate and H2O2 addition and further incubated for 15 mins	ic50	6.7000	uM
1-[[2-[(propan-2-ylamino)methyl]phenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one	1875008: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay	ic50	8.1000	uM

CTD chemical–gene interactions

69 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Methimazole	decreases activity, decreases reaction, affects binding	6
2,2’,4,4’-tetrahydroxybenzophenone	affects binding, decreases activity	3
Benzo(a)pyrene	affects methylation, increases activity, increases mutagenesis	3
Ethylenethiourea	affects activity, decreases activity	3
Propylthiouracil	affects binding, decreases activity, decreases expression	3
captax	affects binding, decreases activity	2
resorcinol	affects binding, decreases activity	2
Arsenic Trioxide	affects binding, decreases reaction, decreases activity, increases reaction	2
Tretinoin	affects expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Genistein	decreases activity	2
daidzein	decreases activity	1
triphenyl phosphate	increases abundance, increases expression	1
propionaldehyde	decreases expression	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
tris(2-butoxyethyl) phosphate	increases expression, increases abundance	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sodium arsenite	increases expression	1
vinclozolin	decreases activity	1
1,2,5,6-dibenzanthracene	increases activity	1
benzo(e)pyrene	increases methylation	1
tris(chloroethyl)phosphate	increases abundance, increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
benzophenone	decreases activity	1
perfluorooctane sulfonic acid	decreases activity	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	affects binding, increases reaction	1
efavirenz	increases expression	1
2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole	decreases expression	1
abrine	increases expression	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3636368	Binding	Inhibition of TPO (unknown origin) using Amplex Red as substrate assessed as formation of resorufin measured every 20 secs by spectrophotometric analysis	Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases. — J Med Chem

Cellosaurus cell lines

6 cell lines: 3 spontaneously immortalized cell line, 3 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E3ED	CHO-HTPO12	Spontaneously immortalized cell line	Female
CVCL_E3EE	CHO-HTPO12b	Spontaneously immortalized cell line	Female
CVCL_E3EF	CHO-HTPO12g	Spontaneously immortalized cell line	Female
CVCL_E3EG	CHO-TPO-M1-K1	Transformed cell line	Female
CVCL_E3EH	CHO-TPO-2B	Transformed cell line	Female
CVCL_E3EI	CHO-TPO-C4C,	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
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
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age