TGFBR2

Summary

TGFBR2 (transforming growth factor beta receptor 2, HGNC:11773) is a protein-coding gene on chromosome 3p24.1, encoding TGF-beta receptor type-2 (P37173). Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3.

The protein encoded by this gene is a transmembrane protein that has a protein kinase domain, forms a heterodimeric complex with TGF-beta receptor type-1, and binds TGF-beta. This receptor/ligand complex phosphorylates proteins, which then enter the nucleus and regulate the transcription of genes related to cell proliferation, cell cycle arrest, wound healing, immunosuppression, and tumorigenesis. Mutations in this gene have been associated with Marfan Syndrome, Loeys-Deitz Aortic Aneurysm Syndrome, and the development of various types of tumors. Alternatively spliced transcript variants encoding different isoforms have been characterized.

Source: NCBI Gene 7048 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Loeys-Dietz syndrome 2 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 19
• Clinical variants (ClinVar): 1,381 total — 50 pathogenic, 58 likely-pathogenic
• Phenotypes (HPO): 177
• Druggable target: yes — 22 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 9 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_003242

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11773
Approved symbol	TGFBR2
Name	transforming growth factor beta receptor 2
Location	3p24.1
Locus type	gene with protein product
Status	Approved
Aliases	TBRII, TBR-ii
Ensembl gene	ENSG00000163513
Ensembl biotype	protein_coding
OMIM	190182
Entrez	7048

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000295754, ENST00000359013, ENST00000672050, ENST00000672866, ENST00000673203, ENST00000673250, ENST00000714389, ENST00000714390, ENST00000714391, ENST00000714392, ENST00000894724, ENST00000941788, ENST00000941789

RefSeq mRNA: 15 — MANE Select: NM_003242 NM_001024847, NM_001407126, NM_001407127, NM_001407128, NM_001407129, NM_001407130, NM_001407132, NM_001407133, NM_001407134, NM_001407135, NM_001407136, NM_001407137, NM_001407138, NM_001407139, NM_003242

CCDS: CCDS2648, CCDS33727

Canonical transcript exons

ENST00000295754 — 7 exons

Exon	Start	End
ENSE00001629075	30650270	30650460
ENSE00001659270	30688384	30688511
ENSE00001734611	30674105	30674246
ENSE00002704195	30606601	30606977
ENSE00002709747	30671638	30672437
ENSE00004023793	30691420	30694142
ENSE00004023797	30644747	30644915

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 122.9258 / max 954.1359, expressed in 1742 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35832	104.5364	1729
35831	14.8343	1631
35830	1.5492	794
35834	0.5989	346
35837	0.4001	189
35840	0.3591	201
35835	0.3485	170
35839	0.2305	94
35829	0.0690	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pericardium	UBERON:0002407	99.65	gold quality
tibia	UBERON:0000979	99.50	gold quality
parietal pleura	UBERON:0002400	99.48	gold quality
pleura	UBERON:0000977	99.34	gold quality
colonic epithelium	UBERON:0000397	99.30	gold quality
lower lobe of lung	UBERON:0008949	99.28	gold quality
visceral pleura	UBERON:0002401	99.12	gold quality
vena cava	UBERON:0004087	99.07	gold quality
superficial temporal artery	UBERON:0001614	99.01	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.98	gold quality
synovial joint	UBERON:0002217	98.86	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.73	gold quality
cardia of stomach	UBERON:0001162	98.71	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.67	gold quality
urethra	UBERON:0000057	98.66	gold quality
peritoneum	UBERON:0002358	98.66	gold quality
omental fat pad	UBERON:0010414	98.66	gold quality
adipose tissue	UBERON:0001013	98.63	gold quality
connective tissue	UBERON:0002384	98.52	gold quality
myocardium	UBERON:0002349	98.49	gold quality
layer of synovial tissue	UBERON:0007616	98.46	gold quality
lung	UBERON:0002048	98.45	gold quality
smooth muscle tissue	UBERON:0001135	98.42	gold quality
descending thoracic aorta	UBERON:0002345	98.42	gold quality
heart right ventricle	UBERON:0002080	98.41	gold quality
gall bladder	UBERON:0002110	98.41	gold quality
pylorus	UBERON:0001166	98.38	gold quality
thoracic mammary gland	UBERON:0005200	98.35	gold quality
mammary gland	UBERON:0001911	98.24	gold quality
right lung	UBERON:0002167	98.23	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	1288.94
E-MTAB-10287	yes	66.71
E-MTAB-10553	yes	47.57
E-HCAD-11	yes	44.24
E-GEOD-134144	yes	39.55
E-CURD-46	yes	35.61
E-HCAD-10	yes	30.87
E-HCAD-1	yes	28.90
E-CURD-119	yes	25.14
E-MTAB-8410	yes	23.81
E-HCAD-9	yes	18.30
E-MTAB-9543	yes	11.00
E-CURD-112	yes	10.54
E-MTAB-9067	yes	8.02
E-HCAD-35	yes	7.06

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF1, ATF2, CEBPA, CEBPB, CREB1, CUX1, DLX2, EGR1, ELF3, ERG, ETS1, ETV1, ETV4, EWSR1, FLI1, FOXO3, H4C2, HDAC2, HOXA10, JUN, KLF14, MEIS1, MEIS2, NFKB, NFYA, NR3C1, PARP1, PAX3, PLAGL1, SIN3A, SMAD2, SMAD3, SNAI1, SNAI2, SP1, SP3, SP6, SPI1, SSRP1

miRNA regulators (miRDB)

185 targeting TGFBR2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Altogether, these results identify a mechanism by which RhoB antagonizes TGF-beta action through transcriptional down-regulation of AP1 in T beta R-II promoter. (PMID:11741970)
• treatment with the HDAC inhibitor induces TbetaRII promoter activity by the recruitment of the PCAF protein to the NF-Y complex, interacting with the inverted CCAAT box in the TbetaRII promoter (PMID:11744689)
• Overexpression of a dominant negatively acting mutant of TGFBR2 in primitive hemopoietic progenitor cells renders them transiently unresponsive to both autocrine and paracrine TGF-beta signaling and leads to their enhanced survival and proliferation. (PMID:11777969)
• TGF beta type II receptor mRNA concentration on the surface of human osteoblasts is increased by 1 alpha,25-dihydroxyvitamin D3 due to changes in receptor mRNA stability not associated with an increase in the rate of gene transcription. (PMID:11820800)
• crystal structure of the human TbetaR2 ectodomain–TGF-beta3 complex (PMID:11850637)
• present in diabetic foot ulcer (PMID:12060054)
• TGFBII receptors were purified and refolded; they have an apparent molecular weight of 14 kDa as by size-exclusion chromatography (PMID:12077447)
• data suggest the existence of a further definite subgroup of diffuse-type gastric carcinomas with altered TGFbeta-IIR expression, independent from a mutator phenotype with TGFbeta-IIR gene mutations (PMID:12174910)
• Differential rates of frameshift alterations in four repeat sequences of hereditary nonpolyposis colorectal cancer tumors.These repeats consisted of (A)10 in the TGF beta RII, (G)8 in the BAX, (A)8 in the CASP1, and (CCA)7 in the APP genes. (PMID:12215842)
• Coding region microsatellite mutations characteristic of defective mismatch repair Identification of TGFbetaRII coding region microsatellite mutations in vivo implicates this gene in the pathogenesis of human T-LBL/ALL. (PMID:12479849)
• This protein was expressed locally in the media and adeventitia at injected arterial segments without any significant dissemination to remote areas. (PMID:12515396)
• TGF-beta2 receptor expression in peritoneal fibroblasts was increased by hypoxia or hypoxia plus TGF-beta1, but decreased by TGF-beta1 alone. (PMID:12607775)
• The loss of TbetaR-II expression in the primary tumor is associated with clinical stage (P <0.01) and predicts a significantly lower survival rate in renal cell carcinoma patients. (PMID:12736050)
• Human breast tumors were screened for TGFBR2 mutation and/or altered expression of TGFBR2 protein. TGFBR2 was expressed in the epithelium and stroma of tumors, and was higher in patients having positive lymph nodes and/or negative ER and PR expression. (PMID:12825850)
• role of a CCAAT box and three GC boxes in the regulation of the TbetaR-II promoters in embryonal carcinoma-differentiated cells (PMID:12840808)
• Transforming growth factor beta1 receptor II is downregulated by E1A in adenovirus-infected cells. (PMID:12915548)
• We observed subsequent loss of type II TGFbeta receptor (TBR2) expression in metastatic renal cell carcinomas [RCC}. We propose that loss of TBR3 is necessary for RCC carcinogenesis, and loss of TBR2 leads to acquisition of a metastatic phenotype. (PMID:12970754)
• ERT mediates the expression of TGF-beta RII, and the transcriptional inhibition of ets-related transcription factor could be a one of the mechanisms of colonic carcinogenesis (PMID:14582709)
• TbetaRII in transgenic mice plays a critical role in maintaining the nondifferentiated character of virgin mammary gland epithelium. (PMID:14601051)
• expression values for TGF 1 and its receptors I, II, and III were twice as high in the group of patients with a diagnosis of high-grade lymphomas as in the group of patients diagnosed with low-grade lymphomas (PMID:14704634)
• TGFBR2 has a role in progression of estrogen receptor-negative breast cancer (PMID:14760070)
• each of the five Ets proteins influences the TbetaR-II promoter in a unique manner because of important differences in their biochemical properties or their patterns of cellular expression (PMID:14976186)
• NMR analysis of the extracellular domain of the human TGFbeta type II receptor in complex with monomeric TGFbeta3 (PMID:15017149)
• combined production of the immunosuppressants IL-10 and TGF-beta, as well as coexpression of TGF-beta RI and RII (required for cellular response to TGF-beta), may act to down-modulate host anti-Mycobacterium tuberculosis immunity (PMID:15102771)
• an increased TGFbetaRI:TGFbetaRII ratio may underlie aberrant TGFbeta signaling in systemic sclerosis and contribute to elevated basal collagen production (PMID:15146427)
• Our studies show that RDH12 is associated with retinal dystrophy and encodes an enzyme with a unique, nonredundant role in the photoreceptor cells. (PMID:15235604)
• The first characterized nonepithelial tumors in hereditary nonpolyposis colorectal cancer seem to carry a limited panel of dna replication errors, including a frameshift at the TGFBR2 gene. (PMID:15350299)
• thrombin via PAR1 induced the internalization of endoglin and type-II TGF-beta receptor (TbetaRII) but not type-I receptors in human ECs (PMID:15522964)
• transforming growth factor beta type II receptor promoter activity and acetylation of Sp1 by recruitment of PCAF/p300 to a Sp1.NF-Y complex are induced by Trichostatin A (PMID:15647279)
• possible role of heterozygous mutation in a newly described human phenotype that includes widespread perturbations in cardiovascular, craniofacial, neurocognitive and skeletal development (PMID:15731757)
• UV-induced down-regulation of TbetaRII and the concerted over-expression of Smad7 may trigger the inhibition of the TGF-beta-induced phosphorylation of Smad2. (PMID:15811425)
• Identification of TGFBR2 mutations in Marfan syndrome type II provided the direct evidence of the relation in humans. (PMID:15861007)
• blockade of TGF-beta after intramuscular transfer of the soluble type II TGF-beta receptor gene suppressed hepatic fibrosis (PMID:15942678)
• Repression of type II TGF-beta receptor may act as significant determinant of lung adenocarcinoma invasiveness, an early step in tumor progression toward metastasis. (PMID:15976377)
• TGFBR2 mutations is associated with deregulation of cdk4 and colon cancer (PMID:16108056)
• Identification of a novel TGFBR2 gene mutation in a Korean patient with Loeys-Dietz aortic aneurysm syndrome; no mutation in TGFBR2 gene in 30 patients with classic Marfan’s syndrome. (PMID:16283890)
• prostate cancer cells mediate growth inhibition and differentiation of bone marrow endothelial cells through alteration of TGFbetaRII-mediated signal transduction. (PMID:16388503)
• changes in TbetaRII levels by EGF are EGF receptor-kinase-dependent and are controlled by signals downstream of MEK1/2 (PMID:16428382)
• Results of this analysis appear to exclude a role for the TGFBR1- or TGFBR2-mediated pathway effect in Kabuki syndrome. (PMID:16528739)
• Down-regulation of TbetaRII in dermal cells or up-regulation of TbetaRII in epidermal cells reverses their migratory responses to serum and plasma, respectively. (PMID:16549496)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tgfbr2b	ENSDARG00000034541
danio_rerio	tgfbr2a	ENSDARG00000059363
danio_rerio		ENSDARG00000113139
mus_musculus	Tgfbr2	ENSMUSG00000032440
rattus_norvegicus	Tgfbr2	ENSRNOG00000013265

Paralogs (11): TGFBR1 (ENSG00000106799), BMPR1A (ENSG00000107779), ACVR2B (ENSG00000114739), ACVR1 (ENSG00000115170), ACVR2A (ENSG00000121989), ACVR1C (ENSG00000123612), AMHR2 (ENSG00000135409), ACVR1B (ENSG00000135503), BMPR1B (ENSG00000138696), ACVRL1 (ENSG00000139567), BMPR2 (ENSG00000204217)

Protein

Protein identifiers

TGF-beta receptor type-2 — P37173 (reviewed: P37173)

Alternative names: TGF-beta type II receptor, Transforming growth factor-beta receptor type II

All UniProt accessions (6): A0AAQ5BI02, A0AAQ5BI03, P37173, A0AAQ5BI06, A3QNQ0, D2JYI1

UniProt curated annotations — full annotation on UniProt →

Function. Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and thus regulates a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. Has transforming growth factor beta-activated receptor activity. Has transforming growth factor beta-activated receptor activity. Binds TGFB1, TGFB2 and TGFB3 in the picomolar affinity range without the participation of additional receptors. Blocks activation of SMAD2 and SMAD3 by TGFB1.

Subunit / interactions. Homodimer. Heterohexamer; TGFB1, TGFB2 and TGFB3 homodimeric ligands assemble a functional receptor composed of two TGFBR1 and TGFBR2 heterodimers to form a ligand-receptor heterohexamer. The respective affinity of TGFRB1 and TGFRB2 for the ligands may modulate the kinetics of assembly of the receptor and may explain the different biological activities of TGFB1, TGFB2 and TGFB3. Component of a complex composed of TSC22D1 (via N-terminus), TGFBR1 and TGFBR2; the interaction between TSC22D1 and TGFBR1 is inhibited by SMAD7 and promoted by TGFB1. Interacts with DAXX. Interacts with DYNLT4. Interacts with ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF-beta receptor. Interacts with and is activated by SCUBE3; this interaction does not affect TGFB1-binding to TGFBR2. Interacts with VPS39; this interaction is independent of the receptor kinase activity and of the presence of TGF-beta. Interacts with CLU. Homodimer; disulfide-linked.

Subcellular location. Cell membrane. Membrane raft Secreted.

Post-translational modifications. Phosphorylated on a Ser/Thr residue in the cytoplasmic domain.

Disease relevance. Hereditary non-polyposis colorectal cancer 6 (HNPCC6) [MIM:614331] An autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term ‘suspected HNPCC’ or ‘incomplete HNPCC’ can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. The disease is caused by variants affecting the gene represented in this entry. Esophageal cancer (ESCR) [MIM:133239] A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage. The disease is caused by variants affecting the gene represented in this entry. Loeys-Dietz syndrome 2 (LDS2) [MIM:610168] An aortic aneurysm syndrome with widespread systemic involvement, characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. Some patients have craniosynostosis, exotropy, micrognathia and retrognathia, structural brain abnormalities, and intellectual deficit. The disease is caused by variants affecting the gene represented in this entry. TGFBR2 mutations Cys-460 and His-460 have been reported to be associated with thoracic aortic aneurysms and dissection (TAAD). This phenotype, also known as thoracic aortic aneurysms type 3 (AAT3), is distinguised from LDS2 by having aneurysms restricted to thoracic aorta. As individuals carrying these mutations also exhibit descending aortic disease and aneurysms of other arteries, they have been considered as LDS2 by the OMIM resource.

Similarity. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P37173-1	1, betaR-II	yes
P37173-2	2, betaR-IIB
P37173-3	3, TbetaRII-SE

RefSeq proteins (15): NP_001020018, NP_001394055, NP_001394056, NP_001394057, NP_001394058, NP_001394059, NP_001394061, NP_001394062, NP_001394063, NP_001394064, NP_001394065, NP_001394066, NP_001394067, NP_001394068, NP_003233* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000333	TGFB_receptor	Family
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR015013	Transforming_GF_b_rcpt_2_ecto	Domain
IPR017194	Transform_growth_fac-b_typ-2	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR045860	Snake_toxin-like_sf	Homologous_superfamily

Pfam: PF07714, PF08917

Enzyme classification (BRENDA):

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor-protein] + ADP + H(+) (RHEA:18673)
• L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor-protein] + ADP + H(+) (RHEA:44880)

UniProt features (109 total): sequence variant 38, strand 23, helix 17, disulfide bond 6, turn 4, modified residue 3, glycosylation site 3, splice variant 3, topological domain 2, binding site 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, region of interest 1, mutagenesis site 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
1M9Z	X-RAY DIFFRACTION	1.05
8G4K	X-RAY DIFFRACTION	1.24
4XJJ	X-RAY DIFFRACTION	1.4
9E9G	X-RAY DIFFRACTION	1.4
4P7U	X-RAY DIFFRACTION	1.5
5QIN	X-RAY DIFFRACTION	1.57
5E8V	X-RAY DIFFRACTION	1.69
5TX4	X-RAY DIFFRACTION	1.88
5E8Y	X-RAY DIFFRACTION	2.05
5E92	X-RAY DIFFRACTION	2.08
8YGZ	X-RAY DIFFRACTION	2.1
1KTZ	X-RAY DIFFRACTION	2.15
7DV6	X-RAY DIFFRACTION	2.39
5E91	X-RAY DIFFRACTION	2.42
5TY4	ELECTRON CRYSTALLOGRAPHY	2.9
3KFD	X-RAY DIFFRACTION	3
2PJY	X-RAY DIFFRACTION	3
9B9F	X-RAY DIFFRACTION	3
9FDY	ELECTRON MICROSCOPY	3.4
9FKP	ELECTRON MICROSCOPY	3.72
9FK5	ELECTRON MICROSCOPY	4.1
1PLO	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P37173-F1	81.22	0.58

Functional residue map

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

Catalytic / active sites (1): 379 (proton acceptor)

Ligand- & substrate-binding residues (2): 250–258; 277

Post-translational modifications (3): 409, 548, 553

Disulfide bonds (6): 51–84, 54–71, 61–67, 77–101, 121–136, 138–143

Glycosylation sites (3): 70, 94, 154

Mutagenesis-validated functional residues (1):

Position	Phenotype
277	abolishes kinase activity, tgf-beta signaling and interaction with daxx.

Function

Pathways and Gene Ontology

Reactome pathways

23 pathways

ID	Pathway
R-HSA-2173788	Downregulation of TGF-beta receptor signaling
R-HSA-2173789	TGF-beta receptor signaling activates SMADs
R-HSA-2173791	TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
R-HSA-3304356	SMAD2/3 Phosphorylation Motif Mutants in Cancer
R-HSA-3642279	TGFBR2 MSI Frameshift Mutants in Cancer
R-HSA-3645790	TGFBR2 Kinase Domain Mutants in Cancer
R-HSA-3656532	TGFBR1 KD Mutants in Cancer
R-HSA-3656535	TGFBR1 LBD Mutants in Cancer
R-HSA-5689603	UCH proteinases
R-HSA-9839389	TGFBR3 regulates TGF-beta signaling
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-170834	Signaling by TGF-beta Receptor Complex
R-HSA-3304349	Loss of Function of SMAD2/3 in Cancer
R-HSA-3304351	Signaling by TGF-beta Receptor Complex in Cancer
R-HSA-3642278	Loss of Function of TGFBR2 in Cancer
R-HSA-3656534	Loss of Function of TGFBR1 in Cancer
R-HSA-392499	Metabolism of proteins
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification
R-HSA-9006936	Signaling by TGFB family members
R-HSA-9839373	Signaling by TGFBR3

MSigDB gene sets: 1081 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, MODULE_52, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, AP1_01, GOBP_EMBRYONIC_HEMOPOIESIS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MAMMARY_GLAND_MORPHOGENESIS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_DENDRITIC_CELL_DIFFERENTIATION, GOBP_CARDIAC_SEPTUM_DEVELOPMENT

GO Biological Process (76): blood vessel development (GO:0001568), branching involved in blood vessel morphogenesis (GO:0001569), vasculogenesis (GO:0001570), in utero embryonic development (GO:0001701), epithelial to mesenchymal transition (GO:0001837), heart looping (GO:0001947), positive regulation of mesenchymal cell proliferation (GO:0002053), lens development in camera-type eye (GO:0002088), positive regulation of tolerance induction to self antigen (GO:0002651), positive regulation of B cell tolerance induction (GO:0002663), positive regulation of T cell tolerance induction (GO:0002666), outflow tract septum morphogenesis (GO:0003148), membranous septum morphogenesis (GO:0003149), outflow tract morphogenesis (GO:0003151), aortic valve morphogenesis (GO:0003180), atrioventricular valve morphogenesis (GO:0003181), tricuspid valve morphogenesis (GO:0003186), cardiac left ventricle morphogenesis (GO:0003214), endocardial cushion fusion (GO:0003274), growth plate cartilage chondrocyte growth (GO:0003430), apoptotic process (GO:0006915), transforming growth factor beta receptor signaling pathway (GO:0007179), Notch signaling pathway (GO:0007219), smoothened signaling pathway (GO:0007224), gastrulation (GO:0007369), nervous system development (GO:0007399), brain development (GO:0007420), heart development (GO:0007507), positive regulation of cell population proliferation (GO:0008284), response to xenobiotic stimulus (GO:0009410), regulation of gene expression (GO:0010468), positive regulation of epithelial cell migration (GO:0010634), positive regulation of epithelial to mesenchymal transition (GO:0010718), activin receptor signaling pathway (GO:0032924), embryonic hemopoiesis (GO:0035162), aorta morphogenesis (GO:0035909), regulation of cell population proliferation (GO:0042127), myeloid dendritic cell differentiation (GO:0043011), positive regulation of angiogenesis (GO:0045766), embryonic cranial skeleton morphogenesis (GO:0048701)

GO Molecular Function (21): protein serine/threonine kinase activity (GO:0004674), transmembrane receptor protein serine/threonine kinase activity (GO:0004675), transforming growth factor beta receptor activity (GO:0005024), transforming growth factor beta receptor activity, type II (GO:0005026), ATP binding (GO:0005524), glycosaminoglycan binding (GO:0005539), activin receptor activity, type I (GO:0016361), kinase activator activity (GO:0019209), type I transforming growth factor beta receptor binding (GO:0034713), type III transforming growth factor beta receptor binding (GO:0034714), SMAD binding (GO:0046332), metal ion binding (GO:0046872), activin binding (GO:0048185), transforming growth factor beta binding (GO:0050431), molecular adaptor activity (GO:0060090), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), signaling receptor activity (GO:0038023)

GO Cellular Component (13): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytosol (GO:0005829), plasma membrane (GO:0005886), caveola (GO:0005901), external side of plasma membrane (GO:0009897), membrane (GO:0016020), nuclear body (GO:0016604), signaling receptor complex (GO:0043235), membrane raft (GO:0045121), activin receptor complex (GO:0048179), transforming growth factor beta ligand-receptor complex (GO:0070021), cell surface (GO:0009986)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Signaling by TGF-beta Receptor Complex in Cancer	3
Signaling by TGF-beta Receptor Complex	2
Loss of Function of TGFBR2 in Cancer	2
Loss of Function of TGFBR1 in Cancer	2
TGF-beta receptor signaling activates SMADs	1
Loss of Function of SMAD2/3 in Cancer	1
Deubiquitination	1
Signaling by TGFBR3	1
Signaling by TGFB family members	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Disease	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
positive regulation of tolerance induction	3
anatomical structure development	2
blood vessel morphogenesis	2
anatomical structure morphogenesis	2
heart valve morphogenesis	2
kinase activity	2
transforming growth factor beta receptor binding	2
binding	2
plasma membrane signaling receptor complex	2
serine/threonine protein kinase complex	2
vasculature development	1
angiogenesis	1
branching morphogenesis of an epithelial tube	1
cell differentiation	1
chordate embryonic development	1
mesenchymal cell differentiation	1
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
positive regulation of cell population proliferation	1
mesenchymal cell proliferation	1
regulation of mesenchymal cell proliferation	1
camera-type eye development	1
tolerance induction to self antigen	1
regulation of tolerance induction to self antigen	1
B cell tolerance induction	1
regulation of B cell tolerance induction	1
T cell tolerance induction	1
regulation of T cell tolerance induction	1
outflow tract morphogenesis	1
cardiac septum morphogenesis	1
ventricular septum morphogenesis	1
heart morphogenesis	1
aortic valve development	1
atrioventricular valve development	1
tricuspid valve development	1
atrioventricular valve morphogenesis	1
cardiac ventricle morphogenesis	1
endocardial cushion morphogenesis	1
cell adhesion involved in heart morphogenesis	1

Protein interactions and networks

STRING

5142 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TGFBR2	TGFB1	P01137	999
TGFBR2	TGFB3	P10600	997
TGFBR2	TGFB2	P08112	997
TGFBR2	ENG	P17813	992
TGFBR2	SMAD3	P84022	986
TGFBR2	TGFBR1	P36897	986
TGFBR2	SMAD2	Q15796	979
TGFBR2	TGFBR3	Q03167	966
TGFBR2	SMAD4	Q13485	961
TGFBR2	ALK	Q9UM73	947
TGFBR2	ACVRL1	P37023	916
TGFBR2	HSP90AA1	P07900	909
TGFBR2	HSP90AB1	P08238	909
TGFBR2	FBN1	P35555	905
TGFBR2	SHC1	P29353	894

IntAct

310 interactions, top by confidence:

A	B	Type	Score
TGFB3	TGFBR2	psi-mi:“MI:0407”(direct interaction)	0.770
AK2	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
TGFBR2	ATP2A3	psi-mi:“MI:0915”(physical association)	0.560
CCT6A	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
TGFBR2	CDH1	psi-mi:“MI:0915”(physical association)	0.560
AP1S1	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
CSNK1D	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
DNASE1L1	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
ELAVL4	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
ETS2	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
GNAO1	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
GPM6A	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
TGFBR2	IDH1	psi-mi:“MI:0915”(physical association)	0.560
TGFBR2	ITGAV	psi-mi:“MI:0915”(physical association)	0.560
STT3A	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
KEL	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
ATXN3	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
TGFBR2	MYC	psi-mi:“MI:0915”(physical association)	0.560
NELL2	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
PPARA	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
PSMD2	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
TGFBR2	PTN	psi-mi:“MI:0915”(physical association)	0.560
RAPSN	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
RPL37A	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
SGCA	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
SUV39H1	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
TCOF1	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
WT1	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
YY1	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (325): CBL (Reconstituted Complex), CBL (Affinity Capture-Western), TGFBR2 (Biochemical Activity), PIK3CB (Affinity Capture-MS), CDC6 (Affinity Capture-MS), PKN3 (Affinity Capture-MS), PLEKHH3 (Affinity Capture-MS), ACVR2B (Affinity Capture-MS), ACVR2A (Affinity Capture-MS), PKN2 (Affinity Capture-MS), TYK2 (Affinity Capture-MS), JAK1 (Affinity Capture-MS), PIK3R2 (Affinity Capture-MS), PIK3R1 (Affinity Capture-MS), PIK3R3 (Affinity Capture-MS)

ESM2 similar proteins: A1A5G2, A4FUF0, A4Q9F4, A6H8I0, A6NNY8, D2HBJ8, E1C1R4, O24454, O94888, P0C8Z3, P15209, P34547, P37173, Q03351, Q0V9G5, Q16620, Q3LAC4, Q49A26, Q504Q3, Q562D5, Q5DU02, Q5R7T2, Q5REY7, Q5RKH0, Q5U252, Q5XGZ2, Q5ZLS7, Q63604, Q6DCJ1, Q6GNI6, Q6IE70, Q6NTR6, Q6P5G6, Q6P9L4, Q70CQ1, Q70EL2, Q70Z35, Q7ZUM8, Q8BGF7, Q8BY87

Diamond homologs: A0A0P0XII1, A0A0R0HPY5, A7J1T2, C0LGD6, C0LGD8, C0LGD9, C0LGG3, C0LGR6, C0LGV0, O00238, O00506, O04086, O35607, O46680, O64556, O65440, P04627, P09560, P0C5E2, P10398, P10533, P14056, P15056, P18161, P20792, P27037, P27038, P27039, P27040, P27041, P27966, P28028, P34908, P36894, P36895, P36896, P36897, P36898, P37023, P37172

SIGNOR signaling

45 interactions.

A	Effect	B	Mechanism
TGFB2	up-regulates	TGFBR2	binding
TGFB3	up-regulates	TGFBR2	binding
DAXX	up-regulates	TGFBR2	binding
HSP90AA1	up-regulates	TGFBR2	binding
SRC	up-regulates	TGFBR2	phosphorylation
LY-2157299	down-regulates	TGFBR2	“chemical inhibition”
SMURF1	“down-regulates activity”	TGFBR2	ubiquitination
SMURF2	“down-regulates activity”	TGFBR2	ubiquitination
TGFBR2	up-regulates	PARD6A	phosphorylation
TGFBR2	“up-regulates activity”	PIK3R1	binding
TGFBR2	up-regulates	PIK3R1	binding
TGFBR2	up-regulates	PIK3R2	binding
TGFBR2	“up-regulates activity”	TGFBR2	phosphorylation
TGFBR2	“up-regulates activity”	ZFYVE9	binding
TGFBR2	“up-regulates activity”	TGFBR1	phosphorylation
TGFBR2	“down-regulates activity”	TGFBR2	phosphorylation
TGFBR2	“up-regulates activity”	PI3K	binding
TGFBR2	up-regulates	PI3K	binding
SMURF	“down-regulates activity”	TGFBR2	ubiquitination
TGFB1	up-regulates	TGFBR2	binding
TGFBR2	up-regulates	TGFBR1	phosphorylation
TGFb	“up-regulates activity”	TGFBR2	binding
hsa-miR-23b-3p	“down-regulates quantity by repression”	TGFBR2	“post transcriptional regulation”
hsa-miR-21-5p	“down-regulates quantity by repression”	TGFBR2	“post transcriptional regulation”

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 9 cancer types — CCRCC, CEAD, CESC, COADREAD, ESCA, HNSC, PAAD, PANCREAS, STAD.

Clinical variants and AI predictions

ClinVar

1381 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	50
Likely pathogenic	58
Uncertain significance	637
Likely benign	384
Benign	45

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1066976	NM_003242.6(TGFBR2):c.1342T>C (p.Tyr448His)	Pathogenic
12501	NM_003242.6(TGFBR2):c.1601_1602dup (p.Ala535fs)	Pathogenic
12503	NM_003242.6(TGFBR2):c.1576G>C (p.Glu526Gln)	Pathogenic
12504	NM_003242.6(TGFBR2):c.1524G>A (p.Gln508=)	Pathogenic
12505	NM_003242.6(TGFBR2):c.923T>C (p.Leu308Pro)	Pathogenic
12506	NM_003242.6(TGFBR2):c.1346C>T (p.Ser449Phe)	Pathogenic
12508	NM_003242.6(TGFBR2):c.1006T>A (p.Tyr336Asn)	Pathogenic
12510	NM_003242.6(TGFBR2):c.1069G>T (p.Gly357Trp)	Pathogenic
12511	NM_003242.6(TGFBR2):c.1583G>A (p.Arg528His)	Pathogenic
12512	NM_003242.6(TGFBR2):c.1582C>T (p.Arg528Cys)	Pathogenic
12514	NM_003242.6(TGFBR2):c.1378C>T (p.Arg460Cys)	Pathogenic
12515	NM_003242.6(TGFBR2):c.1379G>A (p.Arg460His)	Pathogenic
12518	NM_003242.6(TGFBR2):c.1280C>T (p.Pro427Leu)	Pathogenic
12519	NM_003242.6(TGFBR2):c.1483C>T (p.Arg495Ter)	Pathogenic
1299545	NM_003242.6(TGFBR2):c.1582C>A (p.Arg528Ser)	Pathogenic
1386703	NM_003242.6(TGFBR2):c.1558T>C (p.Cys520Arg)	Pathogenic
1386732	NM_003242.6(TGFBR2):c.1610G>C (p.Arg537Pro)	Pathogenic
1456174	NM_003242.6(TGFBR2):c.961T>G (p.Tyr321Asp)	Pathogenic
1470300	NM_003242.6(TGFBR2):c.1378C>G (p.Arg460Gly)	Pathogenic
1514292	NM_003242.6(TGFBR2):c.1152T>G (p.Asn384Lys)	Pathogenic
1686258	NM_003242.6(TGFBR2):c.1447del (p.Cys483fs)	Pathogenic
2104447	NM_003242.6(TGFBR2):c.1133G>A (p.Arg378Lys)	Pathogenic
213929	NM_003242.6(TGFBR2):c.1276G>A (p.Ala426Thr)	Pathogenic
213930	NM_003242.6(TGFBR2):c.1277C>A (p.Ala426Asp)	Pathogenic
213934	NM_003242.6(TGFBR2):c.1489C>T (p.Arg497Ter)	Pathogenic
239528	NM_003242.6(TGFBR2):c.1271A>G (p.Tyr424Cys)	Pathogenic
2574078	NM_003242.6(TGFBR2):c.1330C>T (p.Gln444Ter)	Pathogenic
263412	NM_003242.6(TGFBR2):c.831G>T (p.Lys277Asn)	Pathogenic
263559	NM_003242.6(TGFBR2):c.1136A>T (p.Asp379Val)	Pathogenic
264260	NM_003242.6(TGFBR2):c.1178G>A (p.Cys393Tyr)	Pathogenic

SpliceAI

1987 predictions. Top by Δscore:

Variant	Effect	Δscore
3:30606973:GTCGG:G	donor_gain	1.0000
3:30627370:C:G	donor_gain	1.0000
3:30644743:TCA:T	acceptor_loss	1.0000
3:30644744:CA:C	acceptor_loss	1.0000
3:30644745:A:AG	acceptor_gain	1.0000
3:30644745:AGTT:A	acceptor_loss	1.0000
3:30644746:G:A	acceptor_loss	1.0000
3:30644746:G:GT	acceptor_gain	1.0000
3:30644746:GT:G	acceptor_gain	1.0000
3:30644746:GTT:G	acceptor_gain	1.0000
3:30644746:GTTA:G	acceptor_gain	1.0000
3:30644746:GTTAA:G	acceptor_gain	1.0000
3:30644896:G:GT	donor_gain	1.0000
3:30644911:GTATG:G	donor_gain	1.0000
3:30644913:ATGGT:A	donor_loss	1.0000
3:30644914:TGGT:T	donor_loss	1.0000
3:30644916:G:GA	donor_loss	1.0000
3:30644916:G:GG	donor_gain	1.0000
3:30644917:T:G	donor_loss	1.0000
3:30650457:GAAG:G	donor_gain	1.0000
3:30672438:G:GA	donor_loss	1.0000
3:30672439:T:A	donor_loss	1.0000
3:30674099:CTATA:C	acceptor_loss	1.0000
3:30674100:TATA:T	acceptor_loss	1.0000
3:30674102:TAGGT:T	acceptor_loss	1.0000
3:30674103:A:C	acceptor_loss	1.0000
3:30674103:AGGT:A	acceptor_gain	1.0000
3:30674103:AGGTG:A	acceptor_gain	1.0000
3:30674104:GGT:G	acceptor_gain	1.0000
3:30674104:GGTG:G	acceptor_gain	1.0000

AlphaMissense

3785 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:30644803:T:A	C51S	1.000
3:30644804:G:C	C51S	1.000
3:30644882:G:A	C77Y	1.000
3:30644883:T:G	C77W	1.000
3:30644902:T:C	C84R	1.000
3:30644903:G:A	C84Y	1.000
3:30644904:T:G	C84W	1.000
3:30650307:T:A	C101S	1.000
3:30650308:G:C	C101S	1.000
3:30650309:C:G	C101W	1.000
3:30650367:T:A	C121S	1.000
3:30650368:G:C	C121S	1.000
3:30650414:T:G	C136W	1.000
3:30650420:T:G	C138W	1.000
3:30671940:G:C	G253R	1.000
3:30671946:T:A	F255I	1.000
3:30671946:T:C	F255L	1.000
3:30671946:T:G	F255V	1.000
3:30671947:T:C	F255S	1.000
3:30671947:T:G	F255C	1.000
3:30671948:T:A	F255L	1.000
3:30671948:T:G	F255L	1.000
3:30671949:G:C	A256P	1.000
3:30671950:C:A	A256D	1.000
3:30671971:T:C	L263P	1.000
3:30672007:C:A	A275E	1.000
3:30672010:T:A	V276D	1.000
3:30672012:A:G	K277E	1.000
3:30672014:G:C	K277N	1.000
3:30672014:G:T	K277N	1.000

dbSNP variants (sampled 300 via entrez): RS1000081419 (3:30677883 C>G,T), RS1000111238 (3:30632388 T>G), RS1000113470 (3:30669541 G>T), RS1000113976 (3:30629401 A>G), RS1000169819 (3:30631080 C>G,T), RS1000249248 (3:30632152 C>G,T), RS1000288055 (3:30646863 T>A), RS1000306899 (3:30687682 T>C), RS1000367603 (3:30607480 G>C), RS1000375851 (3:30661050 G>A), RS1000415756 (3:30681572 T>C), RS1000424069 (3:30645007 T>G), RS1000444750 (3:30629035 C>A,T), RS1000475674 (3:30611910 C>G,T), RS1000531706 (3:30651077 A>T)

Disease associations

OMIM: gene MIM:190182 | disease phenotypes: MIM:607086, MIM:610168, MIM:133239, MIM:614331, MIM:154700, MIM:130000, MIM:609192, MIM:194200

GenCC curated gene-disease

Disease	Classification	Inheritance
Loeys-Dietz syndrome 2	Definitive	Autosomal dominant
Loeys-Dietz syndrome	Supportive	Autosomal dominant
familial thoracic aortic aneurysm and aortic dissection	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Loeys-Dietz syndrome 2	Definitive	AD

Mondo (17): familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625), diabetic retinopathy (MONDO:0005266), Loeys-Dietz syndrome 2 (MONDO:0012427), esophageal cancer (MONDO:0007576), colorectal cancer, hereditary nonpolyposis, type 6 (MONDO:0013695), Marfan syndrome (MONDO:0007947), Ehlers-Danlos syndrome (MONDO:0020066), familial colorectal cancer (MONDO:0023113), Loeys-Dietz syndrome (MONDO:0018954), hepatoblastoma (MONDO:0018666), connective tissue disorder (MONDO:0003900), aortic aneurysm, familial thoracic 1 (MONDO:0024559), Loeys-Dietz syndrome 1 (MONDO:0012212), multiple congenital anomalies/dysmorphic syndrome (MONDO:0019042), thoracic aortic aneurysm (MONDO:0005396)

Orphanet (13): Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387), Marfan syndrome type 2 (Orphanet:284973), Marfan syndrome (Orphanet:558), Lynch syndrome (Orphanet:144), Squamous cell carcinoma of the esophagus (Orphanet:99977), Marfan syndrome type 1 (Orphanet:284963), Ehlers-Danlos syndrome (Orphanet:98249), Loeys-Dietz syndrome (Orphanet:60030), Hepatoblastoma (Orphanet:449), Familial aortic dissection (Orphanet:229), Multiple congenital anomalies/dysmorphic syndrome (Orphanet:68341), Furlong syndrome (Orphanet:97295), NON RARE IN EUROPE: Wolff-Parkinson-White syndrome (Orphanet:907)

HPO phenotypes

177 total (30 of 177 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000098	Tall stature
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000202	Orofacial cleft
HP:0000238	Hydrocephalus
HP:0000272	Malar flattening
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000505	Visual impairment
HP:0000520	Proptosis
HP:0000525	Abnormality iris morphology
HP:0000545	Myopia
HP:0000577	Exotropia
HP:0000592	Blue sclerae
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000737	Irritability
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000766	Abnormal sternum morphology
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000822	Hypertension
HP:0000939	Osteoporosis
HP:0000963	Thin skin
HP:0000964	Eczematoid dermatitis
HP:0000965	Cutis marmorata

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000107_7	Tonometry	2.000000e-07
GCST001563_2	Migraine	1.000000e-09
GCST001937_52	Breast cancer	2.000000e-08
GCST002079_32	Migraine - clinic-based	2.000000e-08
GCST002566_6	Response to chemotherapy in breast cancer hypertensive cases (cumulative dose) (bevacizumab)	7.000000e-06
GCST003075_109	Cognitive decline rate in late mild cognitive impairment	1.000000e-06
GCST003075_87	Cognitive decline rate in late mild cognitive impairment	8.000000e-08
GCST003542_42	Night sleep phenotypes	5.000000e-06
GCST003720_1	Migraine	8.000000e-09
GCST004988_221	Breast cancer	7.000000e-14
GCST006624_104	Systolic blood pressure	8.000000e-16
GCST006979_57	Heel bone mineral density	1.000000e-13
GCST007538_2	Cellular nuclear factor (erythroid-derived 2)-like 2 levels	2.000000e-07
GCST008058_39	Estimated glomerular filtration rate	1.000000e-10
GCST008059_252	Estimated glomerular filtration rate	2.000000e-10
GCST009391_1	Metabolite levels	7.000000e-06
GCST009391_1373	Metabolite levels	4.000000e-06
GCST009391_793	Metabolite levels	6.000000e-06
GCST011050_2	Postprandial triglyceride response	2.000000e-06

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0005944	cumulative dose response to bevacizumab
EFO:0007710	cognitive decline measurement
EFO:0006335	systolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0009794	NRF2 measurement
EFO:0009777	citrulline measurement
EFO:0010367	lysophosphatidylethanolamine 18:0 measurement
EFO:0010395	sphingomyelin 22:0 measurement
EFO:0004530	triglyceride measurement

MeSH disease descriptors (11)

Descriptor	Name	Tree numbers
D017545	Aortic Aneurysm, Thoracic	C14.907.055.239.125; C14.907.109.139.125
D003240	Connective Tissue Diseases	C17.300
D003930	Diabetic Retinopathy	C11.768.257; C14.907.320.382; C19.246.099.500.382
D004535	Ehlers-Danlos Syndrome	C14.907.454.240; C15.378.463.515.240; C16.131.831.428; C16.320.850.260; C17.300.200.310; C17.800.804.428; C17.800.827.260
D018197	Hepatoblastoma	C04.557.435.380
D055947	Loeys-Dietz Syndrome	C05.660.207.532; C14.907.055.239.587; C14.907.109.139.587; C16.131.077.537; C16.320.510
D008382	Marfan Syndrome	C05.116.099.674; C14.240.400.725; C14.280.400.725; C16.131.077.550; C16.131.240.400.720; C16.320.540; C17.300.500
D014927	Wolff-Parkinson-White Syndrome	C14.280.067.780.977; C14.280.123.750.977; C16.131.240.400.980
C562834	Aortic Aneurysm, Familial Thoracic 1 (supp.)
C537783	Aortic aneurysm, familial thoracic 3 (supp.)
C566039	Colorectal Cancer, Hereditary Nonpolyposis, Type 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4267 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

22 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 190,862 (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
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1229517	VEMURAFENIB	4	15,704
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL3348923	TOVORAFENIB	4	834
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL5416410	DASATINIB	4	655
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL603469	LESTAURTINIB	3
CHEMBL2364611	GALUNISERTIB	2	1,929
CHEMBL2386889	SCH-900776	2	740
CHEMBL402548	DANUSERTIB	2	1,928
CHEMBL403989	TG100-801	2	249
CHEMBL475251	R-406	2	762
CHEMBL482968	ENMD-2076	2	1,656
CHEMBL495727	AT-9283	2	1,376
CHEMBL296468	BMS-387032	1	2,075
CHEMBL3545083	RGB-286638	1	551
CHEMBL482967	CYC-116	1
CHEMBL574738	AST-487	1

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3087465	Toxicity	3	irinotecan	Colorectal Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3087465	TGFBR2	3	2.50	1	irinotecan

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Type II receptor serine/threonine kinases

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
compound 13a [PMID: 23639540]	Inhibition	8.86	pIC50
compound 13d [PMID: 23639540]	Inhibition	7.59	pIC50
galunisertib	Inhibition	6.68	pIC50
TGFβ3	Agonist	6.53	pKd
LY2109761	Inhibition	6.52	pKi
compound 15b [PMID: 16539403]	Inhibition	6.45	pIC50
H. polygyrus TGF-β mimic	Agonist	5.53	pKd

Binding affinities (BindingDB)

853 measured of 859 human assays (859 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[4-({2-[6-(difluoromethyl)pyridin-2-yl]pyrrolo[2,1-f][1,2,4]triazin-4-yl}amino)pyridin-2-yl]acetamide	IC50	0.19 nM	US-10336761: TGFβ receptor antagonist
N-{5-[(4,4-difluoropiperidin-1-yl)methyl]-2-(6-methylpyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl}-3-fluoropyridin-4-amine	IC50	0.25 nM	US-10336761: TGFβ receptor antagonist
N-(4-{[5-(morpholin-4-ylmethyl)-2-(pyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]amino}pyridin-2-yl)acetamide	IC50	0.25 nM	US-10336761: TGFβ receptor antagonist
US10399987, Example 2	IC50	0.25 nM	US-10399987: TGF beta receptor antagonists
US10399987, Example 33	IC50	0.25 nM	US-10399987: TGF beta receptor antagonists
US10399987, Example 8	IC50	0.26 nM	US-10399987: TGF beta receptor antagonists
3-fluoro-N-(5-{[(1-methylcyclobutyl)amino]methyl}-2-(pyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl)pyridin-4-amine	IC50	0.27 nM	US-10336761: TGFβ receptor antagonist
6-(1-(1-cyanocyclopropyl)-4-(4-fluorophenyl)-1H- imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile	IC50	0.3 nM	US-9884868: TGF-beta inhibitors
2-[(3R)-3-hydroxypyrrolidin-1-yl]-N-[4-({2-[6-(trifluoromethyl)pyridin-2-yl]pyrrolo[2,1-f][1,2,4]triazin-4-yl}amino)pyridin-2-yl]acetamide	IC50	0.3 nM	US-10336761: TGFβ receptor antagonist
N-[4-({2-[6-(trifluoromethyl)pyridin-2-yl]pyrrolo[2,1-f][1,2,4]triazin-4-yl}amino)pyridin-2-yl]cyclopropanecarboxamide	IC50	0.37 nM	US-10336761: TGFβ receptor antagonist
US10399987, Example 31	IC50	0.37 nM	US-10399987: TGF beta receptor antagonists
3-chloro-N-[2-(6-fluoropyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]pyridin-4-amine	IC50	0.39 nM	US-10336761: TGFβ receptor antagonist
6-(4-(4-fluorophenyl)-1-isopropyl-1H-imidazol-5- yl)imidazo[1,2-b]pyridazine-3-carbonitrile	IC50	0.4 nM	US-9884868: TGF-beta inhibitors
6-(4-(3-chloro-4-fluorophenyl)-1-ethyl-1H-imidazol-5- yl)imidazo[1,2-a]pyridine-3-carboxamide	IC50	0.4 nM	US-9884868: TGF-beta inhibitors
6-[2-(6-chloro-2-pyridinyl)-3-pyridinyl]imidazo[1,2-a]pyridine-3-carboxamide	IC50	0.4 nM	US-9981944: GDF-8 inhibitors
N-[4-({5-[(4,4-difluoropiperidin-1-yl)methyl]-2-(pyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl}amino)pyridin-2-yl]acetamide	IC50	0.4 nM	US-10336761: TGFβ receptor antagonist
N-(5-{[(2H-1,3-benzodioxol-5-ylmethyl)amino]methyl}-2-(pyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl)-3-fluoropyridin-4-amine	IC50	0.4 nM	US-10336761: TGFβ receptor antagonist
US10399987, Example 4	IC50	0.42 nM	US-10399987: TGF beta receptor antagonists
N-{2-[6-(difluoromethyl)-5-fluoropyridin-2-yl]pyrrolo[2,1-f][1,2,4]triazin-4-yl}-3-fluoropyridin-4-amine	IC50	0.46 nM	US-10336761: TGFβ receptor antagonist
3-[4-({4-[(3-fluoropyridin-4-yl)amino]-2-(pyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl}methyl)piperazin-1-yl]phenol	IC50	0.47 nM	US-10336761: TGFβ receptor antagonist
(3S)-1-({4-[(3-fluoropyridin-4-yl)amino]-2-(6-methylpyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl}methyl)pyrrolidin-3-ol	IC50	0.49 nM	US-10336761: TGFβ receptor antagonist
6-(4-(3-chloro-4-fluorophenyl)-1-(3-fluorocyclobutyl)- 1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3- carbonitrile	IC50	0.5 nM	US-9884868: TGF-beta inhibitors
6-(4-(4-fluorophenyl)-1-isopropyl-1H-imidazol-5- yl)imidazo[1,2-a]pyridine-3-carboxamide	IC50	0.5 nM	US-9884868: TGF-beta inhibitors
6-(1-cyclobutyl-4-(4-fluorophenyl)-1H-imidazol-5- yl)imidazo[1,2-a]pyridine-3-carboxamide	IC50	0.5 nM	US-9884868: TGF-beta inhibitors
4-[({4-[(3-fluoropyridin-4-yl)amino]-2-(pyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl}methyl)amino]butan-2-ol	IC50	0.52 nM	US-10336761: TGFβ receptor antagonist
US10399987, Example 5	IC50	0.53 nM	US-10399987: TGF beta receptor antagonists
US10399987, Example 10	IC50	0.56 nM	US-10399987: TGF beta receptor antagonists
1-({4-[(3-fluoropyridin-4-yl)amino]-2-(pyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl}methyl)piperidin-4-ol	IC50	0.58 nM	US-10336761: TGFβ receptor antagonist
3-fluoro-N-[2-(pyridin-2-yl)-5-({[2-(pyridin-2-yl)propan-2-yl]amino}methyl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]pyridin-4-amine	IC50	0.58 nM	US-10336761: TGFβ receptor antagonist
3-chloro-N-[2-(5-fluoropyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]pyridin-4-amine	IC50	0.59 nM	US-10336761: TGFβ receptor antagonist
(3S)-1-({2-[6-(difluoromethyl)pyridin-2-yl]-4-[(3-fluoropyridin-4-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-5-yl}methyl)pyrrolidin-3-ol	IC50	0.59 nM	US-10336761: TGFβ receptor antagonist
US10399987, Example 38	IC50	0.59 nM	US-10399987: TGF beta receptor antagonists
6-(4-(4-fluorophenyl)-1-(3- (hydroxymethyl)cyclobutyl)-1H-imidazol-5- yl)imidazo[1,2-b]pyridazine-3-carbonitrile	IC50	0.6 nM	US-9884868: TGF-beta inhibitors
6-(4-(3-chloro-4-fluorophenyl)-1-(2-cylcobutylethyl)- 1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3- carbonitrile	IC50	0.6 nM	US-9884868: TGF-beta inhibitors
6-(4-(3-chloro-4-fluorophenyl)-1-isopropyl-1H- imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile	IC50	0.6 nM	US-9884868: TGF-beta inhibitors
6-(4-(3-chloro-4-fluorophenyl)-1-ethyl-1H-imidazol-5- yl)imidazo[1,2-b]pyridazine-3-carboxamide	IC50	0.6 nM	US-9884868: TGF-beta inhibitors
6-(1-(2,2-difluoropropyl)-4-(4-fluorophenyl)-1H- imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide	IC50	0.6 nM	US-9884868: TGF-beta inhibitors
6-(4-(3-chloro-4-fluorophenyl)-1-(2,2-difluoropropyl)- 1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3- carboxamide	IC50	0.6 nM	US-9884868: TGF-beta inhibitors
6-(1-(1-cyclopropylethyl)-4-(4-fluorophenyl)-1H- imidazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide	IC50	0.6 nM	US-9884868: TGF-beta inhibitors
6-(1-(sec-butyl)-4-(4-fluorophenyl)-1H-imidazol-5- yl)imidazo[1,2-a]pyridine-3-carboxamide	IC50	0.6 nM	US-9884868: TGF-beta inhibitors
6-(4-(3-chloro-4-fluorophenyl)-1-(2,2-difluoroethyl)- 1H-imidazol-5-yl)imidazo[1,2-a]pyridine-3- carboxamide	IC50	0.6 nM	US-9884868: TGF-beta inhibitors
2-[(2-hydroxy-2-methylpropyl)amino]-N-[4-({2-[6-(trifluoromethyl)pyridin-2-yl]pyrrolo[2,1-f][1,2,4]triazin-4-yl}amino)pyridin-2-yl]acetamide	IC50	0.6 nM	US-10336761: TGFβ receptor antagonist
US10399987, Example 11	IC50	0.6 nM	US-10399987: TGF beta receptor antagonists
US10399987, Example 40	IC50	0.6 nM	US-10399987: TGF beta receptor antagonists
US10399987, Example 12	IC50	0.64 nM	US-10399987: TGF beta receptor antagonists
US10399987, Example 39	IC50	0.64 nM	US-10399987: TGF beta receptor antagonists
US10399987, Example 20	IC50	0.67 nM	US-10399987: TGF beta receptor antagonists
6-(1-ethyl-4-(4-fluorophenyl)-1H-imidazol-5- yl)imidazo[1,2-b]pyridazine-3-carboxamide	IC50	0.7 nM	US-9884868: TGF-beta inhibitors
6-(4-(4-fluorophenyl)-1-isopropyl-1H-imidazol-5- yl)imidazo[1,2-b]pyridazine-3-carboxamide	IC50	0.7 nM	US-9884868: TGF-beta inhibitors
6-(4-(3-chloro-4-fluorophenyl)-1-(2-hydroyxethyl)-1H- imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide	IC50	0.7 nM	US-9884868: TGF-beta inhibitors

ChEMBL bioactivities

440 potent at pChembl≥5 of 470 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.51	IC50	0.31	nM	CHEMBL4791414
9.25	IC50	0.56	nM	CHEMBL4758580
9.21	IC50	0.61	nM	CHEMBL4787891
9.08	IC50	0.83	nM	CHEMBL4751832
9.00	IC50	1	nM	CHEMBL4752199
9.00	IC50	1	nM	CHEMBL4748097
8.96	IC50	1.1	nM	CHEMBL4779273
8.92	IC50	1.2	nM	CHEMBL4782729
8.86	IC50	1.37	nM	CHEMBL2385579
8.82	IC50	1.5	nM	CHEMBL4741185
8.80	IC50	1.6	nM	CHEMBL4744618
8.70	IC50	2	nM	CHEMBL4764221
8.54	IC50	2.9	nM	CHEMBL4779579
8.54	IC50	2.9	nM	CHEMBL4763627
8.48	IC50	3.3	nM	CHEMBL4764416
8.44	IC50	3.6	nM	CHEMBL4749061
8.43	IC50	3.7	nM	CHEMBL4744988
8.41	IC50	3.9	nM	CHEMBL4795223
8.30	IC50	5	nM	CHEMBL4798505
8.18	Kd	6.662	nM	CHEMBL5653589
8.15	IC50	7	nM	CHEMBL4289841
8.15	IC50	7	nM	CHEMBL4747422
8.10	IC50	7.9	nM	CHEMBL4777071
8.05	ED50	8.855	nM	CHEMBL5653589
7.84	IC50	14.5	nM	CHEMBL5438171
7.82	IC50	15	nM	CHEMBL2385596
7.82	IC50	15	nM	CHEMBL4750258
7.82	IC50	15	nM	CHEMBL5793463
7.80	IC50	16	nM	CHEMBL2385600
7.80	IC50	16	nM	CHEMBL5769608
7.58	IC50	26	nM	CHEMBL2385582
7.58	IC50	26	nM	CHEMBL6009545
7.44	IC50	36	nM	CHEMBL4763122
7.42	IC50	38	nM	CHEMBL2385586
7.40	IC50	40	nM	CHEMBL4279160
7.30	IC50	50	nM	CHEMBL6037875
7.29	IC50	51	nM	CHEMBL5972103
7.27	Kd	54	nM	ERKi
7.18	IC50	66	nM	SB-431542
7.18	IC50	66	nM	CHEMBL5826016
7.16	IC50	70	nM	CHEMBL5987546
7.12	IC50	75	nM	CHEMBL4783244
7.11	IC50	77	nM	CHEMBL4205311
7.10	Kd	80	nM	RGB-286638
7.10	IC50	80	nM	CHEMBL4205311
7.10	IC50	80	nM	CHEMBL5991561
7.08	IC50	84	nM	CHEMBL6006740
7.00	IC50	100	nM	CHEMBL5866274
7.00	IC50	100	nM	CHEMBL5969135
6.99	IC50	102.9	nM	DORSOMORPHIN

PubChem BioAssay actives

171 with measured affinity, of 746 total; 50 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
1-[3-(2-cyclopropyloxy-4-pyridinyl)-5-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]oxy-2-methylpropan-2-ol	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0003	uM
6-methoxy-5-(1-methylpyrazol-4-yl)-3-(2-propan-2-yloxy-4-pyridinyl)pyrazolo[1,5-a]pyrimidine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0006	uM
3-(2-cyclobutyloxy-4-pyridinyl)-6-methoxy-5-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0006	uM
4-[3-(2-cyclopropyloxy-4-pyridinyl)-5-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]oxy-2-methylbutan-2-ol	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0008	uM
6-methoxy-3-(2-methoxy-4-pyridinyl)-5-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0010	uM
6-methoxy-3-(2-methoxy-4-pyridinyl)-5-propan-2-ylpyrazolo[1,5-a]pyrimidine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0010	uM
6-methoxy-3-(2-methoxy-4-pyridinyl)-N-methylpyrazolo[1,5-a]pyrimidin-5-amine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0010	uM
6-methoxy-3-(2-methoxy-4-pyridinyl)-5-(oxolan-3-yl)pyrazolo[1,5-a]pyrimidine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0011	uM
5-cyclopentyl-6-methoxy-3-(2-methoxy-4-pyridinyl)pyrazolo[1,5-a]pyrimidine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0012	uM
4-[4-[3-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]phenyl]morpholine	750124: Inhibition of TGFBR2 (unknown origin)	ic50	0.0014	uM
6-ethyl-3-(2-methoxy-4-pyridinyl)-N-methylpyrazolo[1,5-a]pyrimidin-5-amine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0015	uM
3-(2-cyclopropyloxy-4-pyridinyl)-6-methoxy-5-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0016	uM
5-[3-(2-cyclopropyloxy-4-pyridinyl)-5-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]oxy-2-methylpentan-2-ol	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0020	uM
5-[6-methoxy-3-(2-methoxy-4-pyridinyl)pyrazolo[1,5-a]pyrimidin-5-yl]-3-methyl-1,2-oxazole	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0029	uM
3-(2-methoxy-4-pyridinyl)-N,6-dimethylpyrazolo[1,5-a]pyrimidin-5-amine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0029	uM
5-[(3S)-5,5-dimethyloxolan-3-yl]-6-methoxy-3-(2-methoxy-4-pyridinyl)pyrazolo[1,5-a]pyrimidine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0030	uM
6-ethenyl-3-(2-methoxy-4-pyridinyl)-N-methylpyrazolo[1,5-a]pyrimidin-5-amine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0030	uM
2-[6-methoxy-3-(2-methoxy-4-pyridinyl)pyrazolo[1,5-a]pyrimidin-5-yl]propan-2-ol	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0033	uM
5-[(3R)-5,5-dimethyloxolan-3-yl]-6-methoxy-3-(2-methoxy-4-pyridinyl)pyrazolo[1,5-a]pyrimidine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0036	uM
6-cyclopropyl-3-(2-methoxy-4-pyridinyl)-N-methylpyrazolo[1,5-a]pyrimidin-5-amine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0037	uM
3-(2-methoxy-4-pyridinyl)-N-methylpyrazolo[1,5-a]pyrimidin-5-amine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0039	uM
6-methoxy-3-(2-methoxy-4-pyridinyl)-5-methylpyrazolo[1,5-a]pyrimidine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0050	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149579: Binding affinity to human TGFBR2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0067	uM
N-[4-[3-(6-fluoro-3-pyridinyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridinyl]acetamide	1423793: Inhibition of wild type TGFbetaR2 (unknown origin) kinase domain after 1 hr by HTRF assay	ic50	0.0070	uM
6-methoxy-3-[2-[(2-methylpropan-2-yl)oxy]-4-pyridinyl]-5-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0070	uM
6-methoxy-3-(2-methoxy-4-pyridinyl)-N,N-dimethylpyrazolo[1,5-a]pyrimidin-5-amine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0079	uM
4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxybenzamide	1992756: Inhibition of TGFbetaR2 (unknown origin) autophosphorylation incubated for 45 to 60 mins in presence of ATP by [33P]-gammaATP based Topcount scintillation counting analysis	ic50	0.0145	uM
6-methoxy-3-(2-methoxy-4-pyridinyl)pyrazolo[1,5-a]pyrimidine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0150	uM
4-[6-[4-(4-methylpiperazin-1-yl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	750124: Inhibition of TGFBR2 (unknown origin)	ic50	0.0150	uM
6-(4-methoxyphenyl)-3-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine	750124: Inhibition of TGFBR2 (unknown origin)	ic50	0.0160	uM
4-[4-(3-quinolin-4-ylpyrazolo[1,5-a]pyrimidin-6-yl)phenyl]morpholine	750124: Inhibition of TGFBR2 (unknown origin)	ic50	0.0260	uM
5-ethyl-6-methoxy-3-(2-methoxy-4-pyridinyl)pyrazolo[1,5-a]pyrimidine	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0360	uM
6-(4-piperazin-1-ylphenyl)-3-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine	750124: Inhibition of TGFBR2 (unknown origin)	ic50	0.0380	uM
N-[4-[3-(6-methoxy-3-pyridinyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridinyl]acetamide	1423793: Inhibition of wild type TGFbetaR2 (unknown origin) kinase domain after 1 hr by HTRF assay	ic50	0.0400	uM
4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1H-imidazol-2-yl]benzamide	709642: Inhibition of TGBR2 signaling in human HEK293T cells assessed as inhibition of SMAD activation after 2 to 22 hrs by dual Luciferase Assay	ic50	0.0660	uM
7,10-dioxa-13,17,18,21-tetrazatetracyclo[12.5.2.12,6.017,20]docosa-1(20),2(22),3,5,14(21),15,18-heptaene	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.0750	uM
2-pyridin-2-yl-N-pyridin-4-ylpyrrolo[2,1-f][1,2,4]triazin-4-amine	1374245: Inhibition of wild type His-tagged TGFbetaR2 (unknown origin) after 1 hr by HTRF assay	ic50	0.0770	uM
1-[3-[4-[[4-(2-methoxyethyl)piperazin-1-yl]methyl]phenyl]-4-oxo-1H-indeno[2,1-d]pyrazol-5-yl]-3-morpholin-4-ylurea	1425197: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0800	uM
6-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine	750124: Inhibition of TGFBR2 (unknown origin)	ic50	0.1029	uM
5-[(3,5-dimethoxyphenyl)methylcarbamoylamino]-3-(pyridin-3-ylmethoxy)-1,2-thiazole-4-carboxamide	1709860: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min	ic50	0.1100	uM
N-(3-fluoro-4-pyridinyl)-2-pyridin-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-amine	1374245: Inhibition of wild type His-tagged TGFbetaR2 (unknown origin) after 1 hr by HTRF assay	ic50	0.1100	uM
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	750124: Inhibition of TGFBR2 (unknown origin)	ic50	0.1404	uM
2-amino-2-cyclohexyl-N-[2-(1-methylpyrazol-4-yl)-9-oxo-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-6-yl]acetamide	1425197: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1460	uM
2-methylpropyl 4-(4-tert-butylphenyl)-2-methyl-5-oxo-7-propyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxylate	709642: Inhibition of TGBR2 signaling in human HEK293T cells assessed as inhibition of SMAD activation after 2 to 22 hrs by dual Luciferase Assay	ic50	0.1700	uM
ethyl 4-(4-tert-butylphenyl)-2-methyl-5-oxo-7-propyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxylate	709642: Inhibition of TGBR2 signaling in human HEK293T cells assessed as inhibition of SMAD activation after 2 to 22 hrs by dual Luciferase Assay	ic50	0.1700	uM
6,8-difluoro-2-methyl-4-[7-(4-piperazin-1-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722089: Inhibition of human TGFBR2 using MBP as substrate by [gamma-33P]-ATP assay	ic50	0.1707	uM
4-[2-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinolin-7-yl]oxyethyl]morpholine	1374245: Inhibition of wild type His-tagged TGFbetaR2 (unknown origin) after 1 hr by HTRF assay	ic50	0.1900	uM
4-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	750124: Inhibition of TGFBR2 (unknown origin)	ic50	0.2360	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624909: Binding constant for TGFBR2 kinase domain	kd	0.2500	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624909: Binding constant for TGFBR2 kinase domain	kd	0.2500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects reaction, decreases expression, increases expression, increases methylation	5
Benzo(a)pyrene	decreases methylation, increases expression, decreases expression	4
Arsenic Trioxide	affects cotreatment, decreases expression	3
Dexamethasone	increases expression, affects cotreatment	3
Cadmium Chloride	decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment	3
bisphenol A	decreases expression, affects cotreatment, increases expression	2
sodium arsenite	decreases expression	2
chloropicrin	decreases expression	2
Resveratrol	decreases reaction, increases expression	2
Arsenic	affects expression, affects methylation	2
Estradiol	increases expression, decreases expression, affects cotreatment	2
Lipopolysaccharides	decreases reaction, increases expression, affects reaction, increases secretion, increases reaction (+3 more)	2
Quercetin	increases expression, decreases expression	2
Rotenone	decreases expression	2
Tretinoin	decreases expression, increases expression	2
Aflatoxin B1	affects cotreatment, decreases expression	2
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
moringin	decreases expression, increases expression	1
methylmercuric chloride	decreases expression	1
deoxynivalenol	decreases expression	1
methylselenic acid	increases expression	1
tolfenamic acid	affects reaction, decreases expression, decreases reaction	1
trichostatin A	affects binding, increases reaction, increases expression	1
beta-lapachone	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	decreases expression	1
benzo(e)pyrene	increases methylation	1

ChEMBL screening assays

188 unique, capped per target: 188 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1045670	Binding	Binding affinity to TGFBR2 assessed as percentage of kinase remaining bound to the bead at 1 uM by T7 phage display based binding assay	Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4). — J Med Chem

Cellosaurus cell lines

2,190 cell lines: 2,185 cancer cell line, 3 embryonic stem cell, 1 transformed cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_0248	DLD-1	Cancer cell line	Male
CVCL_0291	HCT 116	Cancer cell line	Male
CVCL_0397	LS180	Cancer cell line	Female
CVCL_0399	LoVo	Cancer cell line	Male
CVCL_0504	RKO	Cancer cell line	Sex unspecified
CVCL_1331	KM12	Cancer cell line	Male
CVCL_1724	SW48	Cancer cell line	Female
CVCL_1Q94	H414	Cancer cell line	Male
CVCL_1Q95	H414-LIG4(+/-)	Cancer cell line	Male
CVCL_1Q96	H414-MDC1(+/-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00411970	PHASE4	COMPLETED	20- Versus 23- Gauge System for Pars Plana Vitrectomy
NCT00496405	PHASE4	WITHDRAWN	Unilateral Bevacizumab for Bilateral Diabetic Macular Edema
NCT00677664	PHASE4	UNKNOWN	Effects of Copaxone in the Retinal Function in Diabetic Patients After Panphotocoagulation
NCT01223612	PHASE4	COMPLETED	Lucentis (Ranibizumab) in Diabetic Macular Oedema: a Treatment Evaluation
NCT01225653	PHASE4	COMPLETED	Topical Application of Latanoprost in Diabetic Retinopathy
NCT01257815	PHASE4	COMPLETED	Ranibizumab Treatment of Diabetic Macular Oedema With Bimonthly Monitoring After a Phase of Initial Treatment
NCT01306981	PHASE4	COMPLETED	Ranibizumab in Diabetic Vitrectomy. A Prospective, Randomised Controlled Trial of Ranibizumab Pre-treatment in Diabetic Vitrectomy - a Pilot Study
NCT01382498	PHASE4	UNKNOWN	Effect of Doxium on High Sensitivity CRP and Endothelin-1 Serum Levels in Patients With Diabetic Retinopathy
NCT01504724	PHASE4	COMPLETED	Effect of the Adjunctive IVB Before PRP
NCT01591902	PHASE4	TERMINATED	Diabetic Retinopathy in HIV Subjects Treated With EGRIFTA®
NCT01824043	PHASE4	UNKNOWN	Use of Intravitreal Ranibizumab in the Treatment of Vitreous Hemorrhage
NCT01927315	PHASE4	COMPLETED	Effects of Fenofibrate on Endothelial Progenitor Cells in Diabetes
NCT02249897	PHASE4	COMPLETED	PRELIMINARY EVALUATION OF PHARMACOLOGICAL LOWERING OF AGEs
NCT02366468	PHASE4	COMPLETED	Study of Efficacy of Ranibizumab in Different Regimens in Patients With Diabetic Macula Edema
NCT02432547	PHASE4	COMPLETED	Laser Therapy Combined With Intravitreal Aflibercept vs Intravitreal Aflibercept Monotherapy (LADAMO)
NCT02559180	PHASE4	COMPLETED	Treatment of Diabetic Macular Edema With Aflibercept in Subjects Previously Treated With Ranibizumab or Bevacizumab
NCT02647515	PHASE4	COMPLETED	Intravitreal Ranibizumab Injection as Adjuvant in the Treatment of Postvitrectomy Diabetic Vitreous Hemorrhage Accompanied by Neovascular Glaucoma
NCT02874313	PHASE4	COMPLETED	CPAP Effect on the Progression of Diabetic Retinopathy in Patients With Sleep Apnea
NCT03439345	PHASE4	COMPLETED	Lowering Events in Non-proliferative Retinopathy in Scotland
NCT03453281	PHASE4	COMPLETED	Early Anatomical, Physiological, and Clinical Changes in Diabetic Macular Edema After Intravitreal Aflibercept Injection
NCT03962296	PHASE4	COMPLETED	A Multicenter, Randomized, Double-blind Non-inferiority Trial to Evaluate the Efficacy and Safety of Entelon®
NCT04018482	PHASE4	COMPLETED	Povidone Iodine vs AVEnova: A Pre-injection Disinfection Study (PAVE Study)
NCT04038125	PHASE4	UNKNOWN	Increase in Capillary Plexus Density Level Following the Use of Ozurdex for the Treatment of DME
NCT04140201	PHASE4	UNKNOWN	Effect of Lipid Lowering Agents on Diabetic Retinopathy and Cardiovascular Risk of Diabetic Patients
NCT04215445	PHASE4	UNKNOWN	Effect of SGLT2 Inhibition on OCT-A Parameters in Diabetic CKD
NCT04283162	PHASE4	UNKNOWN	Using Calcium Dobesilate to Treat Chinese Patients With Mild to Moderate Non-proliferative Diabetic Retinopathy
NCT04359771	PHASE4	COMPLETED	Transfoveal Micropulse Laser for Center Involving Diabetic Macular Edema
NCT04448496	PHASE4	UNKNOWN	Prospective Trial of Dexamethasone implAnt for Treatment Naïve diabeTic Macular Edema
NCT04619303	PHASE4	COMPLETED	Intravitreal Dexamethasone vs Bevacizumab in Aboriginal People With DMO
NCT04674254	PHASE4	COMPLETED	Macular Perfusion Changes After Anti-VEGF Versus Targeted Retinal Photocoagulation in Proliferative Diabetic Retinopathy
NCT04708145	PHASE4	COMPLETED	Long-Term Efficacy and Safety of Intravitreal Aflibercept Injections for the Treatment of Diabetic Retinopathy for Subjects Who Completed the 2-Year PANORAMA Trial
NCT04991350	PHASE4	TERMINATED	Effect of Ranibizumab Versus Bevacizumab on the Macular Perfusion in Diabetic Macular Edema
NCT05386160	PHASE4	UNKNOWN	Phacoemulsification Combined With Intravitreal Injection of Ranibizumab Prevent Postoperative Capillary Non-perfusion Zone Progress in Non-proliferative Diabetic Retinopathy
NCT06191094	PHASE4	ENROLLING_BY_INVITATION	Pre-operative Vabysmo in Patients With Non-clearing Vitreous Hemorrhage Secondary to Proliferative Diabetic Retinopathy
NCT06660940	PHASE4	NOT_YET_RECRUITING	Clinical Trial of Keluoxin Capsules in the Treatment of Diabetic Kidney Disease with Diabetic Retinopathy
NCT06708637	PHASE4	COMPLETED	Ocular Safety and Usability Study for FYB203 PFS
NCT07090044	PHASE4	COMPLETED	Comparing Post-intravitreal Injection Pain Scores Using Loteprednol, Bromfenac Sodium, and Artificial Tears Over a 24-hour Period
NCT07301775	PHASE4	NOT_YET_RECRUITING	Comparing Single Versus Multiple Anti-VEGF Injections in Diabetic Patients Undergoing Cataract Surgery
NCT07456826	PHASE4	ENROLLING_BY_INVITATION	Study Evaluating the Efficacy and Safety of Chloroprocaine HCl Ophthalmic Gel 3% vs Proparacaine Ophthalmic Solution 0.5% Plus Subconjunctival Lidocaine in Patients Undergoing Intravitreal Injections
NCT00000151	PHASE3	COMPLETED	Early Treatment Diabetic Retinopathy Study (ETDRS)