THPO

Summary

THPO (thrombopoietin, HGNC:11795) is a protein-coding gene on chromosome 3q27.1, encoding Thrombopoietin (P40225). Lineage-specific cytokine affecting the proliferation and maturation of megakaryocytes from their committed progenitor cells.

Megakaryocytopoiesis is the cellular development process that leads to platelet production. The main functional protein encoded by this gene is a humoral growth factor that is necessary for megakaryocyte proliferation and maturation, as well as for thrombopoiesis. This protein is the ligand for MLP/C_MPL, the product of myeloproliferative leukemia virus oncogene. Mutations in this gene are the cause of thrombocythemia 1. Alternative promoter usage and differential splicing result in multiple transcript variants differing in the 5’ UTR and/or coding region. Multiple AUG codons upstream of the main open reading frame (ORF) have been identified, and these upstream AUGs inhibit translation of the main ORF at different extent.

Source: NCBI Gene 7066 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital amegakaryocytic thrombocytopenia (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 34 (top 3% of genes corpus-wide)
• Clinical variants (ClinVar): 763 total — 49 pathogenic, 48 likely-pathogenic (top 4% of genes corpus-wide)
• GTEx eGene: eQTL in 11 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 72
• ChEMBL bioactivity: 103 clinical-phase molecules tested; no curated mechanism-of-action drug
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.12 (unconstrained)
• MANE Select transcript: NM_000460

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11795
Approved symbol	THPO
Name	thrombopoietin
Location	3q27.1
Locus type	gene with protein product
Status	Approved
Aliases	TPO, MPLLG
Ensembl gene	ENSG00000090534
Ensembl biotype	protein_coding
OMIM	600044
Entrez	7066

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 16 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000647395

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3

ENST00000647395, ENST00000421442, ENST00000445696, ENST00000477594, ENST00000645603, ENST00000648612, ENST00000649095, ENST00000650229, ENST00000876539, ENST00000876540, ENST00000876541, ENST00000876542, ENST00000876543, ENST00000876544, ENST00000962183, ENST00000992664, ENST00001111155, ENST00001111156

RefSeq mRNA: 10 — MANE Select: NM_000460 NM_000460, NM_001177597, NM_001177598, NM_001289997, NM_001289998, NM_001290003, NM_001290022, NM_001290026, NM_001290027, NM_001290028

CCDS: CCDS3265, CCDS54693, CCDS77867, CCDS93431, CCDS93432

Canonical transcript exons

ENST00000647395 — 6 exons

Exon	Start	End
ENSE00000781177	184375515	184375601
ENSE00000781178	184373415	184373582
ENSE00001056827	184376247	184376404
ENSE00001079331	184375888	184376015
ENSE00001288988	184371935	184373178
ENSE00003827644	184378075	184378207

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 91.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4646 / max 68.0802, expressed in 125 samples.

Highest expression (Bgee): lobe of liver, liver, hemisphere of cerebellum, frontal lobe, cerebellar hemisphere.

Genetic regulation across tissues (GTEx eQTL / sQTL)

THPO is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

11 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellar Hemisphere	eqtl	3.1e-05	-0.27	3:184359769:T:C
Esophagus Muscularis	eqtl	1.8e-03	+0.29	3:184741711:G:A
Testis	eqtl	3.0e-03	-0.15	3:184378790:A:G
Lung	eqtl	7.6e-03	+0.81	3:183534467:G:A
Brain Cerebellum	eqtl	7.7e-03	-0.23	3:184503767:C:T
Skin Sun Exposed Lower leg	eqtl	9.4e-03	+0.43	3:184366477:A:G
Brain Cortex	eqtl	1.4e-02	-0.19	3:184372478:C:T
Adipose Subcutaneous	eqtl	1.6e-02	-0.19	3:184379297:A:G
Thyroid	eqtl	2.2e-02	-0.15	3:184367270:T:C
Colon Sigmoid	eqtl	2.4e-02	-0.19	3:184407006:G:A
Artery Aorta	eqtl	2.8e-02	-0.24	3:184386115:A:C

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
45892	0.2796	73
45894	0.1427	51
45893	0.0383	23
45891	0.0040	2

Top tissues by expression

showing 100 of 291 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	91.67	gold quality
liver	UBERON:0002107	79.83	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.11	gold quality
right frontal lobe	UBERON:0002810	75.89	gold quality
cerebellar hemisphere	UBERON:0002245	75.48	gold quality
cerebellar cortex	UBERON:0002129	75.18	gold quality
cerebellum	UBERON:0002037	72.12	gold quality
body of uterus	UBERON:0009853	71.83	gold quality
cingulate cortex	UBERON:0003027	71.01	gold quality
anterior cingulate cortex	UBERON:0009835	70.86	gold quality
Brodmann (1909) area 9	UBERON:0013540	69.78	gold quality
endocervix	UBERON:0000458	68.69	gold quality
right adrenal gland	UBERON:0001233	68.69	gold quality
right ovary	UBERON:0002118	68.55	gold quality
left adrenal gland	UBERON:0001234	68.34	gold quality
apex of heart	UBERON:0002098	68.26	gold quality
gastrocnemius	UBERON:0001388	68.20	gold quality
right adrenal gland cortex	UBERON:0035827	68.15	gold quality
left adrenal gland cortex	UBERON:0035825	67.99	gold quality
left ovary	UBERON:0002119	67.87	gold quality
amygdala	UBERON:0001876	67.67	gold quality
muscle of leg	UBERON:0001383	67.48	gold quality
hindlimb stylopod muscle	UBERON:0004252	67.46	gold quality
adult mammalian kidney	UBERON:0000082	67.23	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	67.22	gold quality
prefrontal cortex	UBERON:0000451	66.21	gold quality
adrenal cortex	UBERON:0001235	66.09	gold quality
metanephros cortex	UBERON:0010533	65.89	gold quality
omental fat pad	UBERON:0010414	65.32	gold quality
peritoneum	UBERON:0002358	65.25	gold quality
neocortex	UBERON:0001950	65.01	gold quality
mucosa of stomach	UBERON:0001199	64.73	gold quality
left uterine tube	UBERON:0001303	64.73	gold quality
smooth muscle tissue	UBERON:0001135	64.55	gold quality
frontal cortex	UBERON:0001870	64.41	gold quality
adrenal gland	UBERON:0002369	64.35	gold quality
muscle organ	UBERON:0001630	64.26	gold quality
ectocervix	UBERON:0012249	64.14	gold quality
adipose tissue of abdominal region	UBERON:0007808	64.00	gold quality
diaphragm	UBERON:0001103	63.76	gold quality
left coronary artery	UBERON:0001626	63.75	gold quality
ovary	UBERON:0000992	62.98	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	62.98	gold quality
cerebral cortex	UBERON:0000956	62.44	gold quality
coronary artery	UBERON:0001621	62.32	gold quality
lower esophagus muscularis layer	UBERON:0035833	62.19	gold quality
lower esophagus	UBERON:0013473	62.11	gold quality
right coronary artery	UBERON:0001625	61.89	gold quality
tibial nerve	UBERON:0001323	61.53	gold quality
mucosa of paranasal sinus	UBERON:0005030	61.36	gold quality
subcutaneous adipose tissue	UBERON:0002190	61.21	gold quality
vena cava	UBERON:0004087	61.20	gold quality
right testis	UBERON:0004534	60.91	gold quality
heart left ventricle	UBERON:0002084	60.76	gold quality
left testis	UBERON:0004533	60.53	gold quality
body of pancreas	UBERON:0001150	60.37	gold quality
telencephalon	UBERON:0001893	60.35	gold quality
right atrium auricular region	UBERON:0006631	60.20	gold quality
cardiac ventricle	UBERON:0002082	60.08	gold quality
tibial artery	UBERON:0007610	60.01	gold quality
stromal cell of endometrium	CL:0002255	59.99	gold quality
popliteal artery	UBERON:0002250	59.99	gold quality
myometrium	UBERON:0001296	59.88	gold quality
vagina	UBERON:0000996	59.85	gold quality
brain	UBERON:0000955	59.72	gold quality
central nervous system	UBERON:0001017	59.49	gold quality
uterine cervix	UBERON:0000002	59.41	gold quality
nucleus accumbens	UBERON:0001882	59.37	gold quality
cardiac atrium	UBERON:0002081	59.32	gold quality
mammary duct	UBERON:0001765	59.04	gold quality
heart	UBERON:0000948	58.97	gold quality
forebrain	UBERON:0001890	58.83	gold quality
testis	UBERON:0000473	58.67	gold quality
aorta	UBERON:0000947	58.51	gold quality
kidney	UBERON:0002113	58.45	gold quality
epithelium of mammary gland	UBERON:0003244	58.45	gold quality
temporal lobe	UBERON:0001871	58.38	gold quality
gluteal muscle	UBERON:0002000	58.26	gold quality
spleen	UBERON:0002106	58.18	gold quality
colonic epithelium	UBERON:0000397	58.17	silver quality
epithelium of nasopharynx	UBERON:0001951	58.12	gold quality
triceps brachii	UBERON:0001509	58.07	gold quality
putamen	UBERON:0001874	58.00	gold quality
right lobe of thyroid gland	UBERON:0001119	57.96	gold quality
adipose tissue	UBERON:0001013	57.92	gold quality
vastus lateralis	UBERON:0001379	57.88	gold quality
female reproductive system	UBERON:0000474	57.81	gold quality
superficial temporal artery	UBERON:0001614	57.63	gold quality
cortex of kidney	UBERON:0001225	57.47	gold quality
uterus	UBERON:0000995	57.46	gold quality
body of stomach	UBERON:0001161	57.43	gold quality
quadriceps femoris	UBERON:0001377	57.42	gold quality
Ammon’s horn	UBERON:0001954	57.38	gold quality
connective tissue	UBERON:0002384	57.31	gold quality
thoracic aorta	UBERON:0001515	56.78	gold quality
ascending aorta	UBERON:0001496	56.77	gold quality
muscle layer of sigmoid colon	UBERON:0035805	56.72	gold quality
descending thoracic aorta	UBERON:0002345	56.71	gold quality
caudate nucleus	UBERON:0001873	56.18	gold quality
primary visual cortex	UBERON:0002436	55.97	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.09

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 115 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thyroid gland	tissue	989.4	high
Liver	tissue	16.8
Spleen	tissue	12.5	not detected
Cerebral cortex	tissue	9.0
Insular cortex	tissue	9.0
Prefrontal cortex	tissue	8.0
Retrosplenial cortex	tissue	8.0
Hippocampal formation	tissue	7.6
Entorhinal cortex	tissue	7.6
Retrosplenial and cingulate cortex	tissue	7.6
Motor cortex	tissue	7.1
Temporal cortex	tissue	7.1
Amygdala	tissue	5.3
Occipital cortex	tissue	5.2
Tongue	tissue	5.2
Somatosensory cortex	tissue	5.0
Heart muscle	tissue	4.8	not detected
Spinal cord	tissue	4.3
Skeletal muscle	tissue	4.2	not detected
Basal ganglia	tissue	4.0
Corpus callosum	tissue	3.8
Olfactory bulb	tissue	3.7
Substantia nigra	tissue	3.3
Putamen	tissue	3.2
Periaqueductal gray	tissue	3.2
Medulla oblongata	tissue	2.9
Gallbladder	tissue	2.8	not detected
Pons	tissue	2.7
Hypothalamus	tissue	2.7
Ventral forebrain	tissue	2.7
Septum	tissue	2.7
Superior colliculi	tissue	2.6
Hippocampus	tissue	2.5
Postcentral gyrus	tissue	2.5
Midbrain	tissue	2.4
Thalamus	tissue	2.2
Cerebellum	tissue	2.2
Adipose tissue	tissue	2.1	not detected
Testis	tissue	1.9
Vagina	tissue	1.9
Endometrium 1	tissue	1.9
Kidney	tissue	1.8
Skeletal muscle	tissue	1.7
Smooth muscle	tissue	1.4
Adipose tissue	tissue	1.3
Frontal cortex	tissue	1.3
Nucleus accumbens	tissue	1.3
Lymph node	tissue	1.3	not detected
Epididymis	tissue	1.2
Postcentral gyrus	tissue	1.1
Ovary	tissue	1.0
Cervix	tissue	0.9
Tongue	tissue	0.9
Locus coeruleus	tissue	0.8
Breast	tissue	0.8	not detected
Vagina	tissue	0.8	not detected
Esophagus	tissue	0.8	not detected
Rectum	tissue	0.8	not detected
Pituitary gland	tissue	0.7
Adrenal gland	tissue	0.7

Brain sub-regions (HPA Brain Atlas): detected in 375; highest nTPM — Ventral hippocampus (6.6), Dorsal hippocampus (6.3), Corticomedial amygdala (6.1), Subiculum (5.3), Basal amygdala (5.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A, IRF2, JUN, MYC, SPI1

miRNA regulators (miRDB)

Targeting THPO by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 58 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-3678-3P	99.31	67.10	1432

Functional genomics

gnomAD constraint: pLI 0.000551, LOEUF 1.12, missense Z 1.46 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000647395 — one region, missense o/e 0.85. ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Jak-Stat and PI 3-kinase activation pathways regulate the TPO-induced survival of megakaryocytic cells via Bcl-xL gene expression. (PMID:11756417)
• Mutations in the 5’ untranslated region of the TPO gene are not the cause of the normal or elevated TPO levels in acquired essential thrombocythemia. (PMID:11860444)
• Overexpreeeion of human thrombopoietin increased the platelet level in the transfected mice. (PMID:11877062)
• REVIEW: central role in the pathogenesis of idiopathic thrombocytopenic purpura (ITP), andother immune-mediated thrombocytopenias. (PMID:11913997)
• While there is increased platelet turnover in patients with chronic renal failure, the kidney does not seem to play a major role in the overall Tpo production in the body. (PMID:11960394)
• binding to platelet thrombopoietin receptor is directly involved in human thrombopoietin plasma level regulation (PMID:11961237)
• Flt3/Flk-2-ligand in synergy with thrombopoietin may slow down megakaryocyte development by causing increased proliferation of megakaryocyte progenitor cells. (PMID:11983110)
• In the presence of EPO and SCF and/or IL-3, TPO enhances bone marrow erythropoiesis in cell cultures derived from patients with Diamond-Blackfan anemia. (PMID:12041668)
• Thrombopoietin activates MAPKp42/44, AKT, and STAT proteins in normal human CD34+ cells, megakaryocytes, and platelets. (PMID:12135673)
• The endogenous levels of TPO, IL-6 and IL-8 are elevated in the thrombocytopenic patients with AML and MDS. (PMID:12187073)
• induces megakaryocyte-specific glycoprotein VI promoter and its regulation by GATA-1, Fli-1, and Sp1 (PMID:12359731)
• no difference was found in the cord blood level of thrombopoietin between infants born to mothers with pregnancy-induced hypertension and those without (PMID:12381927)
• Platelet signaling pathways activated by thrombopoietin may affect mitochondrial transcription via activation of mitochondrial STAT3 (PMID:12389630)
• review of TPO role in thrombopoiesis, signal transduction, cellular proliferative and anti-apoptotic mechanisms increasing megakaryocyte numbers (PMID:12430879)
• levels in children with acute and chronic idiopathic thrombocytopenic purpura and its relationship with mega-dose methylprednisolone therapy (PMID:12468916)
• Tpo concentrations in plasma samples taken concurrently from the right ventricle, the pulmonary artery, and the left ventricle showed there were positive correlations between the Tpo levels and pulmonary artery systolic pressure. (PMID:12487786)
• TPO stimulation of a megakaryocyte cell line activated lyn kinase, shown to be involved in the transduction pathway of the TPO proliferative signal. (PMID:12495897)
• Production of this protein in human hepatic cell cultures is not affected by IFN-alpha, IFN-beta, and IFN-gamma. (PMID:12581491)
• c-mpl mutations are the cause not only for the hypomegakaryocytic thrombocytopenia, but also for the development of an aplastic anemia (AA) in patients with CAMT (PMID:12799278)
• Hematopoietic stem cell self-renewal and expansion is reduced 10-20-fold after transplantation of normal stem cells into thrombopoietin null mice (PMID:12799280)
• identification of a potential “silencer” sequence in intron 5 of the TPO gene (PMID:12829024)
• results suggest that one mechanism of thrombocytopenia in patients with cGVHD is low TPO production by BM cells (PMID:12879435)
• Thrombopoietin cooperates with FLT3-L, inducing CD34+ HPCs to undergo a 400-fold expansion in cell numbers. (PMID:14670916)
• Increased serum TPO levels in patients with thrombocytosis in lung cancer which may be related to the activity of neoplasms. (PMID:14689068)
• structure-function relationships in TPO and the activation scheme of c-Mpl (PMID:14769915)
• IL-1beta up-regulates the expression of TPO in megakaryocytic cells. (PMID:14966463)
• The maximal promoter activity of c-mpl was obtained 24 hr after pretreatment with TPO for 3 hr (PMID:14995067)
• Decreased production of platelets by megakaryocytes due to low thrombopoietin concentration could be a possible cause of thrombocytopenia in liver cirrhosis. (PMID:15239259)
• Thrombopoietin induces HOXA9 nuclear transport in immature hematopoietic cells (PMID:15254242)
• Altered regulation of the TPO gene might be involved in the pathogenesis of familial thrombocytosis. (PMID:15282677)
• The Thrombopoietin altered expression provide an opportunity to diagnose and identify subpopulations of MPD patients. (PMID:15572213)
• expression of TPO receptor on platelets until 1 month after birth cause a decreased TPO clearance and keep a high level of free TPO in blood, resulting in the subsequent thrombocytosis in preterm infants. (PMID:15647951)
• mechanisms by which THPO can influence stem cell development (PMID:15705785)
• The effect of THPO on HuMCs in the presence of rhSCF varies, depending on the relative concentration of each growth factor, while THPO alone or in combination with rhSCF supports a unique population of CD117low/CD110+ HuMCs. (PMID:15781331)
• TPO integrates G(i), but not G(q), stimulation, supports integrin alpha(IIb)beta(3) activation platelet aggregation independently of phospholipase C but requires PI3-kinase and Rap1B (PMID:15863506)
• Data describe coculture of human peripheral blood cells and mouse stromal cells transfected with c-kit ligand, thrombopoietin, flt-3/flk2 ligand, and granulocyte-macrophage-CSF or with weekly addition of these cytokines. (PMID:16305336)
• in patients with AML, inadequate TPO levels are secondary to TPO clearing by functional c-mpl receptor myeloid blast cells and that TPO may serve as an in vivo myeloid leukemic growth factor (PMID:16317100)
• Preoperative serum thrombopoietin levels are higher in patients with ovarian cancer than with benign cysts (PMID:16359773)
• in HIV infected patients, both the serum thrombopoietin (TPO) levels and the TPO-c-Mpl complexes on the platelet surface were significantly elevated (PMID:16454716)
• FISH study showed no cytogenetic abnormalities in any of the analyzed cases. (PMID:16682284)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	thpo	ENSDARG00000079158
mus_musculus	Thpo	ENSMUSG00000022847
rattus_norvegicus	Thpo	ENSRNOG00000046850

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:101875) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased mean platelet volume	2
thrombocytopenia	2
abnormal cranium morphology	1
cornea opacity	1
increased pulmonary respiratory rate	1
decreased pulmonary ventilation	1
decreased megakaryocyte cell number	1
decreased bronchoconstrictive response	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Canis lupus familiaris	P42705	88.0%	Diamond
Sus scrofa	P42706	88.0%	Diamond
Epinephelus coioides	Q5IGQ0	81.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC01840	ncRNA	100874079
LINC01839	ncRNA	105374251
CHRD	protein-coding	8646
FAM131A	protein-coding	131408
EIF4G1	protein-coding	1981
POLR2H	protein-coding	5437
PSMD2	protein-coding	5708
SNORD66	snoRNA	692107
CLCN2	protein-coding	1181
LINC02054	ncRNA	105374250

Protein

Protein identifiers

Thrombopoietin — P40225 (reviewed: P40225)

Alternative names: C-mpl ligand, Megakaryocyte colony-stimulating factor, Megakaryocyte growth and development factor, Myeloproliferative leukemia virus oncogene ligand

All UniProt accessions (5): A0A2R8Y734, A0A3B3ITS0, P40225, F8W6L1, Q5FBX8

UniProt curated annotations — full annotation on UniProt →

Function. Lineage-specific cytokine affecting the proliferation and maturation of megakaryocytes from their committed progenitor cells. It acts at a late stage of megakaryocyte development. It may be the major physiological regulator of circulating platelets.

Subunit / interactions. Interacts with MPL/TPOR.

Subcellular location. Secreted.

Disease relevance. Thrombocythemia 1 (THCYT1) [MIM:187950] A myeloproliferative disorder characterized by excessive platelet production, resulting in increased numbers of circulating platelets. It can be associated with spontaneous hemorrhages and thrombotic episodes. The disease is caused by variants affecting the gene represented in this entry. Amegakaryocytic thrombocytopenia, congenital, 2 (CAMT2) [MIM:620481] A form of congenital amegakaryocytic thrombocytopenia, a hematologic disorder characterized by severe reduction of megakaryocytes and platelets at birth, and evolving into generalized bone marrow aplasia during childhood. CAMT2 is an autosomal recessive form. Most patients present with thrombocytopenia that progresses to pancytopenia. The disease is caused by variants affecting the gene represented in this entry. Thrombocytopenia 9 (THC9) [MIM:620478] A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC9 is an autosomal dominant form characterized by low platelet counts in the absence of significant bleeding tendency. Some individuals may have mild mucocutaneous bleeding, whereas others may be asymptomatic. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Two-domain structure with an erythropoietin-like N-terminal and a Ser/Pro/Thr-rich C-terminal.

Similarity. Belongs to the EPO/TPO family.

Isoforms (3)

UniProt ID	Names	Canonical?
P40225-1	1	yes
P40225-2	2, TPO-2
P40225-3	3, Truncated

RefSeq proteins (10): NP_000451, NP_001171068, NP_001171069, NP_001276926, NP_001276927, NP_001276932, NP_001276951, NP_001276955, NP_001276956, NP_001276957 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001323	EPO_TPO	Family
IPR003978	Thrombopoietin	Family
IPR009079	4_helix_cytokine-like_core	Homologous_superfamily
IPR019767	EPO/TPO_CS	Conserved_site

Pfam: PF00758

UniProt features (55 total): glycosylation site 14, helix 11, sequence variant 7, sequence conflict 6, strand 5, compositionally biased region 3, disulfide bond 2, splice variant 2, turn 2, signal peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
1V7M	Human Thrombopoietin Functional Domain Complexed To Neutralizing Antibody TN1 Fab	X-RAY DIFFRACTION	2.51
1V7N	Human Thrombopoietin Functional Domain Complexed To Neutralizing Antibody TN1 Fab	X-RAY DIFFRACTION	3.3
8G04	Structure of signaling thrombopoietin-MPL receptor complex	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40225-F1	61.61	0.22

Antibody-complex structures (SAbDab)

2 antibodies co-crystallized with this protein: 1V7M, 1V7N

Human Protein Atlas

Protein class: Predicted membrane proteins, Predicted secreted proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, Human disease related genes

Protein evidence: Evidence at protein level

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)

Type	Positions
Disulfide bond	28–172, 50–106

Glycosylation sites (14)

Type	Positions
O-linked (galnac…) threonine	180, 213, 58, 131, 179
O-linked (galnac…) serine	184, 265, 22
N-linked (glcnac…) (complex) asparagine	197, 206, 234, 255
N-linked (glcnac…) asparagine	340, 348

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-109582	Hemostasis	—
R-HSA-76009	Platelet Aggregation (Plug Formation)	electronic
R-HSA-76002	Platelet activation, signaling and aggregation	—

MSigDB gene sets: 416 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_EMBRYONIC_HEMOPOIESIS, chr2p25, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_MYELOID_CELL_DEVELOPMENT, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_PLATELET_AGGREGATION_PLUG_FORMATION, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GCANCTGNY_MYOD_Q6, GOBP_HYDROGEN_PEROXIDE_CATABOLIC_PROCESS, MODULE_64, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE

GO Biological Process (14): positive regulation of protein phosphorylation (GO:0001934), cell population proliferation (GO:0008283), positive regulation of cell population proliferation (GO:0008284), megakaryocyte differentiation (GO:0030219), megakaryocyte development (GO:0035855), thrombopoietin-mediated signaling pathway (GO:0038163), positive regulation of MAPK cascade (GO:0043410), positive regulation of megakaryocyte differentiation (GO:0045654), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cell surface receptor signaling pathway via STAT (GO:0097696), positive regulation of hematopoietic stem cell proliferation (GO:1902035), regulation of hemopoiesis (GO:1903706), signal transduction (GO:0007165)

GO Molecular Function (5): signaling receptor binding (GO:0005102), cytokine activity (GO:0005125), hormone activity (GO:0005179), growth factor activity (GO:0008083), protein binding (GO:0005515)

GO Cellular Component (1): extracellular region (GO:0005576)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Platelet activation, signaling and aggregation	1
Hemostasis	1

GO top-level categories

38 GO namespaces:

Category	Terms
receptor ligand activity	3
cellular process	2
megakaryocyte differentiation	2
positive regulation of intracellular signal transduction	2
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
myeloid cell differentiation	1
myeloid cell development	1
chemokine-mediated signaling pathway	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of myeloid cell differentiation	1
regulation of megakaryocyte differentiation	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
cell surface receptor signaling pathway	1
hematopoietic stem cell proliferation	1
regulation of hematopoietic stem cell proliferation	1
positive regulation of stem cell proliferation	1
regulation of immune system process	1
hemopoiesis	1
regulation of cell development	1
regulation of multicellular organismal development	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
protein binding	1
binding	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
cell surface receptor signaling pathway via STAT	BP	direct assay
megakaryocyte development	BP	direct assay
megakaryocyte differentiation	BP	direct assay
positive regulation of MAPK cascade	BP	direct assay
positive regulation of cell population proliferation	BP	direct assay
positive regulation of hematopoietic stem cell proliferation	BP	direct assay
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	BP	direct assay
regulation of hemopoiesis	BP	direct assay
thrombopoietin-mediated signaling pathway	BP	direct assay
cytokine activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,290 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THPO	MPL	P40238	967
THPO	KITLG	P21583	950
THPO	IL3	P08700	911
THPO	FLT3LG	P49771	909
THPO	EPO	P01588	907
THPO	CD34	P28906	892
THPO	CSF3	P09919	846
THPO	JAK2	O60674	793
THPO	IL6	P05231	791
THPO	SH2B3	Q9UQQ2	766
THPO	ITGA2B	P08514	741
THPO	CXCL12	P48061	725
THPO	IL11	P20809	720
THPO	CSF2	P04141	715
THPO	EPOR	P19235	712

IntAct

Human interaction partners of THPO in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
MPL	direct interaction	0.600	3
ECE1	physical association	0.370	2
APH1A	physical association	0.370	1
EP300	physical association	0.370	1
NUMBL	physical association	0.370	1

BioGRID (6 interactions; top human partners by supporting records): APH1A (Two-hybrid), EP300 (Two-hybrid), NUMBL (Two-hybrid), S100A6 (Reconstituted Complex), S100P (Reconstituted Complex), SPPL3 (Positive Genetic)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
THPO	up-regulates	MPL	binding

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ MPL-THPO complex	2	MPL, THPO

Ligand–receptor pairs (CellPhoneDB) (2)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

2 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
THRB
MPL	ligand

Disease & clinical

Genetic variants

Variant evidence for THPO: 763 ClinVar records (97 pathogenic / likely pathogenic); 34 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	49
Likely pathogenic	48
Uncertain significance	228
Likely benign	317
Benign	36

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 97 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
429301	NM_001206744.2(TPO):c.1184_1187dup (p.Ala397fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	20
4044	NM_001206744.2(TPO):c.1357T>G (p.Tyr453Asp)	Pathogenic	criteria provided, multiple submitters, no conflicts	9
1064772	NM_001206744.2(TPO):c.1477G>A (p.Gly493Ser)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
1323705	NM_001206744.2(TPO):c.31_50dup (p.Glu17fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
2734130	NM_001206744.2(TPO):c.1993C>T (p.Arg665Trp)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
1701830	NM_001206744.2(TPO):c.265C>T (p.Arg89Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
623380	NM_001206744.2(TPO):c.2421del (p.Cys808fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2581320	NM_001206744.2(TPO):c.2492T>G (p.Leu831Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
374344	NM_001206744.2(TPO):c.1994G>A (p.Arg665Gln)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
3584378	NM_001206744.2(TPO):c.482+1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2070998	NM_000460.4(THPO):c.295C>T (p.Arg99Trp)	Pathogenic	criteria provided, single submitter	3
4054	NM_001206744.2(TPO):c.1955dup (p.Phe653fs)	Pathogenic	criteria provided, single submitter	2
520806	NM_000460.4(THPO):c.112C>T (p.Arg38Cys)	Pathogenic	criteria provided, single submitter	2
872935	NM_000460.4(THPO):c.-47del	Pathogenic	criteria provided, single submitter	2
623381	NM_001206744.2(TPO):c.764dup (p.Gly256fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore THPO’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 2,678):

Position(s)	Effect	Δscore	Sites
2:1414503–1414504	donor_loss	1.0000	2
2:1423130–1423131	donor_loss	1.0000	5
2:1433436	acceptor_loss	1.0000	3
2:1456074–1456075	acceptor_loss	1.0000	5
2:1456283–1456284	donor_loss	1.0000	4
2:1484855–1484856	donor_loss	1.0000	5
2:1491392	donor_gain	1.0000
2:1496198–1496199	donor_loss	1.0000	4
3:184374493	donor_gain	1.0000
2:1414503–1414504	donor_loss	0.9900	3

AlphaMissense

306 missense substitutions predicted likely pathogenic (of 2,206 scored), across 99 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F149	8	0.935	0.989
F67	8	0.887	0.981
D29	8	0.862	0.947
W72	7	0.966	0.998
C50	7	0.950	0.983
F162	7	0.932	0.983
C28	7	0.921	0.960
C106	7	0.895	0.933
F152	7	0.863	0.958
C172	7	0.855	0.908
D66	7	0.803	0.885
D39	7	0.777	0.873
K159	6	0.956	0.980
P63	6	0.891	0.964
K35	6	0.854	0.947
K80	6	0.852	0.979
G158	5	0.921	0.955
D83	5	0.780	0.864
V160	5	0.649	0.775
L156	4	0.907	0.963

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Liver Hepatocellular Carcinoma)

Disease associations

OMIM: gene MIM:600044 | disease phenotypes: MIM:274500, MIM:620478, MIM:620481, MIM:187950

GenCC curated gene-disease

6 curated gene-disease records:

Disease	Classification	Inheritance	Records
thrombocythemia 1	Strong	Autosomal dominant	4
thyroid dyshormonogenesis 2A	Strong	Autosomal recessive	2
thrombocytopenia 9	Strong	Autosomal dominant
hereditary thrombocytosis with transverse limb defect	Supportive	Autosomal dominant
familial thrombocytosis	Supportive	Autosomal dominant
familial thyroid dyshormonogenesis	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

2 validity classifications:

Disease	Classification	Inheritance
congenital amegakaryocytic thrombocytopenia	Definitive	SD
thrombocythemia 1	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (6 panels, 4 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

6 panels:

Panel	Rating
Bleeding and platelet disorders	green
Cytopenia - NOT Fanconi anaemia	green
Inherited bleeding disorders	green
Thrombocythaemia	green
Limb disorders	amber
Paediatric disorders	amber

Mondo (10): thyroid dyshormonogenesis 2A (MONDO:0010133), neurodevelopmental disorder (MONDO:0700092), congenital hypothyroidism (MONDO:0018612), thrombocytopenia (MONDO:0002049), thrombocytopenia 9 (MONDO:0957572), amegakaryocytic thrombocytopenia, congenital, 2 (MONDO:0957575), thrombocythemia 1 (MONDO:0008554), hereditary thrombocytosis with transverse limb defect (MONDO:0018000), familial thrombocytosis (MONDO:0019111), familial thyroid dyshormonogenesis (MONDO:0010132)

Orphanet (2): Familial thyroid dyshormonogenesis (Orphanet:95716), Congenital hypothyroidism (Orphanet:442)

HPO phenotypes

showing 60 of 72 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
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:0000975	Hyperhidrosis
HP:0000989	Pruritus
HP:0001123	Visual field defect
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001260	Dysarthria
HP:0001265	Hyporeflexia
HP:0001279	Syncope
HP:0001537	Umbilical hernia
HP:0001662	Bradycardia
HP:0001744	Splenomegaly
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001876	Pancytopenia
HP:0001892	Abnormal bleeding
HP:0001894	Thrombocytosis
HP:0001903	Anemia
HP:0001915	Aplastic anemia
HP:0002019	Constipation
HP:0002045	Hypothermia
HP:0002092	Pulmonary arterial hypertension
HP:0002315	Headache
HP:0002321	Vertigo
HP:0002326	Transient ischemic attack
HP:0002637	Cerebral ischemia
HP:0002863	Myelodysplasia
HP:0002925	Elevated circulating thyroid-stimulating hormone concentration
HP:0003265	Neonatal hyperbilirubinemia
HP:0003401	Paresthesia
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0004420	Arterial thrombosis
HP:0004491	Large posterior fontanelle
HP:0004808	Acute myeloid leukemia
HP:0004866	Impaired ADP-induced platelet aggregation
HP:0004936	Venous thrombosis
HP:0004950	Peripheral arterial stenosis
HP:0005268	Miscarriage
HP:0005280	Depressed nasal bridge
HP:0005506	Chronic myelogenous leukemia
HP:0005528	Bone marrow hypocellularity
HP:0005930	Abnormal epiphysis morphology
HP:0006254	Elevated circulating alpha-fetoprotein concentration
HP:0006579	Prolonged neonatal jaundice
HP:0008148	Impaired epinephrine-induced platelet aggregation
HP:0008263	Thyroid defect in oxidation and organification of iodide
HP:0008320	Impaired collagen-induced platelet aggregation
HP:0008828	Delayed proximal femoral epiphyseal ossification

GWAS associations

showing 30 of 34 associations:

Study	Trait	p-value
GCST90002400_171	Plateletcrit	1e-168
GCST90002402_733	Platelet count	2e-138
GCST90002400_175	Plateletcrit	9e-109
GCST90002400_173	Plateletcrit	1e-85
GCST90002402_736	Platelet count	4e-82
GCST004607_213	Plateletcrit	4e-74
GCST004607_214	Plateletcrit	5e-71
GCST90002402_743	Platelet count	1e-67
GCST004607_216	Plateletcrit	4e-65
GCST004603_189	Platelet count	7e-65
GCST004603_188	Platelet count	5e-63
GCST004607_215	Plateletcrit	9e-63
GCST004603_190	Platelet count	4e-51
GCST004603_191	Platelet count	2e-50
GCST006101_12	Cardiometabolic and hematological traits	2e-50
GCST005991_5	Platelet count	7e-50
GCST90002402_734	Platelet count	7e-45
GCST90002400_172	Plateletcrit	3e-43
GCST007932_50	Medication use (thyroid preparations)	6e-25
GCST010571_82	Autoimmune thyroid disease	1e-21
GCST002378_1	Thyroid peroxidase antibody positivity	2e-16
GCST90002400_174	Plateletcrit	1e-14
GCST003988_13	Hypothyroidism	6e-14
GCST010653_31	Thyroid stimulating hormone levels	1e-13
GCST90002402_735	Platelet count	2e-13
GCST002373_1	Thyroid peroxidase antibody levels	7e-13
GCST000580_3	Platelet count	5e-11
GCST002416_1	Thyroid peroxidase antibody positivity	1e-10
GCST006898_5	Hypothyroidism	2e-10
GCST90002397_687	Mean spheric corpuscular volume	4e-10

EFO canonical traits (from GWAS)

5 canonical traits:

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0006995	response to diisocyanate
EFO:0007985	platelet crit
EFO:0008344	response to placebo
EFO:0009933	Thyroid preparation use measurement

MeSH disease descriptors

5 disease descriptors:

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
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C564766	Thyroid Dyshormonogenesis 1 *(supp.)*
C563206	Thyroid Dyshormonogenesis 2A *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293256 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 999,667 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 103 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL600	ACETYLCYSTEINE	4	96,284
CHEMBL633	AMIODARONE	4	30,023
CHEMBL1113	AMOXAPINE	4	20,303
CHEMBL43	AMSACRINE	4	83,286
CHEMBL1489	AZACITIDINE	4	98,570
CHEMBL1095292	BRETYLIUM TOSYLATE	4	3,070
CHEMBL1370	BUDESONIDE	4	73,656
CHEMBL1560	CAPTOPRIL	4	66,788
CHEMBL1201236	CARBIDOPA ANHYDROUS	4	25,411
CHEMBL515	CHLORAMBUCIL	4	173,945
CHEMBL71	CHLORPROMAZINE	4	46,206
CHEMBL1371	CHLORZOXAZONE	4	16,875
CHEMBL799	CILOSTAZOL	4	20,168
CHEMBL1626	CLEMASTINE	4	17,696
CHEMBL415	CLOMIPRAMINE	4	27,595
CHEMBL104	CLOTRIMAZOLE	4	56,839
CHEMBL107	COLCHICINE	4	94,904
CHEMBL669	CYCLOBENZAPRINE	4	11,772
CHEMBL333826	DEQUALINIUM	4	1,128
CHEMBL72	DESIPRAMINE	4	35,148
CHEMBL1123	DICYCLOMINE	4
CHEMBL657	DIPHENHYDRAMINE	4
CHEMBL932	DIPYRIDAMOLE	4
CHEMBL964	DISULFIRAM	4
CHEMBL59	DOPAMINE	4
CHEMBL1256958	EPINEPHRINE BITARTRATE	4
CHEMBL710	FINASTERIDE	4
CHEMBL185	FLUOROURACIL	4
CHEMBL726	FLUPHENAZINE	4
CHEMBL46516	FLUSPIRILENE	4
CHEMBL54	HALOPERIDOL	4
CHEMBL276832	HYDRALAZINE	4
CHEMBL537	HYDROQUINONE	4
CHEMBL818	IOBENGUANE	4
CHEMBL157101	KETOCONAZOLE	4
CHEMBL960	LEFLUNOMIDE	4
CHEMBL677	LEVONORDEFRIN	4
CHEMBL841	LOPERAMIDE	4
CHEMBL998	LORATADINE	4
CHEMBL21731	MAPROTILINE	4
CHEMBL313972	MASOPROCOL	4
CHEMBL267936	MECAMYLAMINE	4
CHEMBL45816	MIBEFRADIL	4
CHEMBL58	MITOXANTRONE	4
CHEMBL1200326	NICARDIPINE HYDROCHLORIDE	4
CHEMBL1448	NICLOSAMIDE	4
CHEMBL193	NIFEDIPINE	4
CHEMBL445	NORTRIPTYLINE	4
CHEMBL428647	PACLITAXEL	4
CHEMBL6067650	PAROXETINE HYDROCHLORIDE	4
CHEMBL361506	PENTAMIDINE ISETHIONATE	4
CHEMBL567	PERPHENAZINE	4
CHEMBL1423	PIMOZIDE	4
CHEMBL2	PRAZOSIN	4
CHEMBL728	PROCHLORPERAZINE	4
CHEMBL103	PROGESTERONE	4
CHEMBL564	PROMAZINE	4
CHEMBL668	PROTRIPTYLINE	4
CHEMBL1590	PSEUDOEPHEDRINE	4
CHEMBL81	RALOXIFENE	4

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

542 potent at pChembl≥5 of 834 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.40	Potency	4	nM	CHEMBL1448979
8.40	Potency	4	nM	CHEMBL1406446
8.00	Potency	10	nM	BUDESONIDE
8.00	Potency	10	nM	CHEMBL1435477
7.90	Potency	12.6	nM	FLUOROURACIL
7.90	Potency	12.6	nM	NOCODAZOLE
7.60	Potency	25.1	nM	CHEMBL1515691
7.60	Potency	25.1	nM	MITOXANTRONE
7.50	Potency	31.6	nM	CHEMBL1518927
7.40	Potency	39.8	nM	CHEMBL1330659
7.40	Potency	39.8	nM	HYDRALAZINE
7.40	Potency	39.8	nM	DIPHENYLENEIODONIUM
7.30	Potency	50.1	nM	CHEMBL1355952
7.20	Potency	63.1	nM	CHEMBL1435868
7.20	Potency	63.1	nM	DIPHENHYDRAMINE
7.20	Potency	63.1	nM	CHEMBL296455
7.10	Potency	79.4	nM	CHEMBL405358
7.00	Potency	100	nM	NICLOSAMIDE
7.00	Potency	100	nM	CHEMBL1255755
6.90	Potency	125.9	nM	CHEMBL156747
6.90	Potency	125.9	nM	HYDRAZINECARBOXAMIDE
6.90	Potency	125.9	nM	CHLORZOXAZONE
6.90	Potency	125.9	nM	CAMPTOTHECIN
6.80	Potency	158.5	nM	CHEMBL1437221
6.80	Potency	158.5	nM	KENPAULLONE
6.70	Potency	199.5	nM	CHEMBL322970
6.60	Potency	251.2	nM	CHEMBL355496
6.60	Potency	251.2	nM	CHEMBL1397711
6.60	Potency	251.2	nM	SOBUZOXANE
6.60	Potency	251.2	nM	CHEMBL1472903
6.50	Potency	316.2	nM	CHEMBL1553718
6.50	Potency	316.2	nM	RUTAECARPINE
6.50	Potency	316.2	nM	DEXPROPRANOLOL
6.40	Potency	398.1	nM	DISULFIRAM
6.40	Potency	398.1	nM	CHEMBL1315323
6.40	Potency	398.1	nM	CHEMBL35482
6.30	Potency	501.2	nM	COLCHICINE
6.30	Potency	501.2	nM	CHEMBL1365553
6.30	Potency	501.2	nM	OLEOYL DOPAMINE
6.30	Potency	501.2	nM	APIGENIN
6.20	Potency	631	nM	CHEMBL1255867
6.10	Potency	794.3	nM	CHEMBL1441136
6.10	Potency	794.3	nM	IMETIT
6.00	Potency	1000	nM	CHEMBL66654
6.00	Potency	1000	nM	CHEMBL297784
6.00	Potency	1000	nM	LINOPIRDINE
6.00	Potency	1000	nM	CHEMBL56543
6.00	Potency	1000	nM	CHEMBL1315342
6.00	Potency	1000	nM	CHEMBL101168
6.00	Potency	1000	nM	SANGUINARIUM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
Acetaminophen	affects expression, decreases expression	2
Benzo(a)pyrene	decreases expression, affects methylation	2
dicrotophos	increases expression	1
diphenyleneiodonium	decreases reaction, increases phosphorylation	1
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid	decreases reaction, increases abundance, increases expression	1
testosterone undecanoate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
anagrelide	decreases reaction, increases expression	1
nickel chloride	affects cotreatment, increases secretion	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
CGP 52608	affects binding, increases reaction	1
alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide	decreases reaction, increases expression	1
U 0126	decreases reaction, increases expression	1
entinostat	increases expression	1
pyrazolanthrone	increases expression, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
StemRegenin 1	affects cotreatment, increases activity	1
10-(4’-(N-diethylamino)butyl)-2-chlorophenoxazine	decreases reaction, increases expression	1
Resveratrol	affects cotreatment, increases activity	1
Gemcitabine	increases expression	1
Acetylcysteine	decreases reaction, increases abundance, increases expression	1
Cadmium	decreases expression	1
Calcitriol	decreases expression	1
Dioxins	increases expression	1
Lipopolysaccharides	affects cotreatment, increases secretion	1
Methamphetamine	increases expression	1
Tetradecanoylphorbol Acetate	affects expression, affects cotreatment	1

ChEMBL screening assays

2 unique, capped per target: 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1614034	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Identification of Small Molecule Antagonists for Thrombopoietin (TPO) Signaling Pathway. (Class of assay: confirmatory) [Related pubchem assays: 917 ]	PubChem BioAssay data set

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 235 trials:

NCT	Phase	Status	Title
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	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	Phase 4	TERMINATED	Use of Tirosint®-SOL or Tablet Formulations of Levothyroxine in Pediatric Patients With Congenital Hypothyroidism (CH)
NCT05371262	Phase 4	COMPLETED	Influence of Initial Levothyroxine Dose on Neurodevelopmental and Growth Outcomes in Congenital Hypothyroidism
NCT07754370	Phase 4	COMPLETED	Levothyroxine Dosing in Neonatal Congenital Hypothyroidism
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	Phase 1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT03655223	Not specified	ACTIVE_NOT_RECRUITING	Early Check: Expanded Screening in Newborns
NCT01783041	Phase 2/3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	Phase 2/3	COMPLETED	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	Early Phase 1	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	COMPLETED	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
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice
NCT03381027	Not specified	COMPLETED	BABY SMART (Study of Massage Therapy, Sleep And neurodevelopMenT)
NCT03388294	Not specified	COMPLETED	Evaluation of a Novel Intervention for Infants At Risk for Neurodevelopmental Disorders
NCT03410810	Not specified	UNKNOWN	Childhood Outcomes of Preterm Brain Abnormalities
NCT03492060	Not specified	RECRUITING	Longitudinal Study of Neurogenetic Disorders
NCT03577756	Not specified	COMPLETED	Neurodevelopmental Assessment of Infants With Cystic Fibrosis
NCT03654248	Not specified	COMPLETED	Let’s Get Organized in Adult Psychiatric/habilitation Care
NCT03659279	Not specified	COMPLETED	Let’s Get Organized Feasibility Study
NCT03722615	Not specified	COMPLETED	Epidemiology of Congenital Cytomegalovirus in a High HIV Prevalence Setting, South Africa
NCT03770832	Not specified	ACTIVE_NOT_RECRUITING	Wearable Sensors and Video Recordings to Monitor Motor Development
NCT03830879	Not specified	RECRUITING	Shenzhen Birth Cohort Study
NCT03835689	Not specified	COMPLETED	Strongest FamiliesTM Neurodevelopmental
NCT03882788	Not specified	COMPLETED	The Effect of Anesthesia on Neurodevelopmental Outcome (NDO)
NCT03922087	Not specified	COMPLETED	No-worry Baby Project
NCT03977259	Not specified	ACTIVE_NOT_RECRUITING	Targeting Human Milk Fortification to Improve Preterm Infant Growth and Brain Development
NCT04043572	Not specified	UNKNOWN	The Biomarkers of Neurological Disease in Utero Study
NCT04096430	Not specified	RECRUITING	Evaluation of Effectiveness of Child-oriented Goal-setting in Paediatric Rehabilitation (the ENGAGE Approach)

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for THPO across ~30M SureChEMBL compounds — explore on Sugi Predict.