TGFBR1

Summary

TGFBR1 (transforming growth factor beta receptor 1, HGNC:11772) is a protein-coding gene on chromosome 9q22.33, encoding TGF-beta receptor type-1 (P36897). Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene forms a heteromeric complex with type II TGF-beta receptors when bound to TGF-beta, transducing the TGF-beta signal from the cell surface to the cytoplasm. The encoded protein is a serine/threonine protein kinase. Mutations in this gene have been associated with Loeys-Dietz aortic aneurysm syndrome (LDAS). Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7046 — RefSeq curated summary.

At a glance

• Gene–disease (curated): multiple self-healing squamous epithelioma (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 13
• Clinical variants (ClinVar): 1,192 total — 53 pathogenic, 53 likely-pathogenic
• Phenotypes (HPO): 109
• Druggable target: yes — 28 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004612

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11772
Approved symbol	TGFBR1
Name	transforming growth factor beta receptor 1
Location	9q22.33
Locus type	gene with protein product
Status	Approved
Aliases	ALK-5, ACVRLK4, ALK5, TBRI, TBR-i
Ensembl gene	ENSG00000106799
Ensembl biotype	protein_coding
OMIM	190181
Entrez	7046

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 18 protein_coding, 8 nonsense_mediated_decay, 1 retained_intron

ENST00000374990, ENST00000374994, ENST00000546584, ENST00000547314, ENST00000548365, ENST00000549021, ENST00000549766, ENST00000550253, ENST00000552516, ENST00000552573, ENST00000698941, ENST00000698942, ENST00000698943, ENST00000714345, ENST00000714346, ENST00000714347, ENST00000714348, ENST00000714349, ENST00000714350, ENST00000714351, ENST00000858563, ENST00000858564, ENST00000937285, ENST00000937286, ENST00000937287, ENST00000937288, ENST00000971225

RefSeq mRNA: 24 — MANE Select: NM_004612 NM_001130916, NM_001306210, NM_001407416, NM_001407417, NM_001407418, NM_001407419, NM_001407420, NM_001407422, NM_001407423, NM_001407424, NM_001407425, NM_001407426, NM_001407427, NM_001407428, NM_001407429, NM_001407430, NM_001407432, NM_001407433, NM_001407434, NM_001407435, NM_001407436, NM_001407437, NM_001407438, NM_004612

CCDS: CCDS47998, CCDS6738, CCDS78413, CCDS94447

Canonical transcript exons

ENST00000374994 — 9 exons

Exon	Start	End
ENSE00002328871	99132509	99132739
ENSE00003459200	99128855	99129100
ENSE00004013645	99137859	99138089
ENSE00004013646	99147654	99147784
ENSE00004013647	99149180	99154192
ENSE00004013648	99144732	99144888
ENSE00004013649	99142536	99142703
ENSE00004013650	99146485	99146609
ENSE00004023696	99105113	99105302

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 97.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.6609 / max 1085.4831, expressed in 1799 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97647	16.8691	1778
97652	6.5639	1452
97646	1.6074	1039
97651	1.2319	608
97649	0.8577	404
97650	0.5308	281

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	97.46	gold quality
tibia	UBERON:0000979	96.97	gold quality
visceral pleura	UBERON:0002401	95.73	gold quality
calcaneal tendon	UBERON:0003701	95.47	gold quality
synovial joint	UBERON:0002217	94.67	gold quality
mammary duct	UBERON:0001765	94.21	gold quality
ventricular zone	UBERON:0003053	94.02	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.89	gold quality
superficial temporal artery	UBERON:0001614	93.49	gold quality
ganglionic eminence	UBERON:0004023	93.49	gold quality
gingival epithelium	UBERON:0001949	92.97	gold quality
gingiva	UBERON:0001828	92.92	gold quality
dorsal root ganglion	UBERON:0000044	92.88	gold quality
amniotic fluid	UBERON:0000173	92.73	gold quality
germinal epithelium of ovary	UBERON:0001304	92.71	gold quality
trigeminal ganglion	UBERON:0001675	92.65	gold quality
lower lobe of lung	UBERON:0008949	92.38	gold quality
parietal pleura	UBERON:0002400	92.17	gold quality
epithelium of nasopharynx	UBERON:0001951	92.10	gold quality
pleura	UBERON:0000977	91.92	gold quality
skin of hip	UBERON:0001554	91.86	gold quality
tendon	UBERON:0000043	91.45	gold quality
placenta	UBERON:0001987	91.34	gold quality
trabecular bone tissue	UBERON:0002483	91.20	gold quality
adrenal tissue	UBERON:0018303	91.08	gold quality
esophagus squamous epithelium	UBERON:0006920	90.84	gold quality
ascending aorta	UBERON:0001496	90.66	gold quality
thoracic aorta	UBERON:0001515	90.51	gold quality
pericardium	UBERON:0002407	90.32	gold quality
cartilage tissue	UBERON:0002418	90.32	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8559	yes	323.55
E-HCAD-35	yes	32.17
E-HCAD-25	yes	15.63
E-ANND-3	yes	8.76
E-GEOD-124858	no	2390.99

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
SERPINE1	Activation

Upstream regulators (CollecTRI, top): ACVRL1, ETS1, FOXH1, KLF4, PARP1, PPARG, RUNX2, SIX1, SMAD2, SMAD7, SP1, TFAP2A, TGFB1, WWP1

miRNA regulators (miRDB)

328 targeting TGFBR1, 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-4262	100.00	73.26	3931
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4500	99.99	72.72	2367
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-371B-5P	99.99	75.34	4759
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-373-5P	99.98	75.36	4753

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• TGF beta type I 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 associaed with an increase in the rate of gene transcription. (PMID:11820800)
• present in diabetic foot ulcer (PMID:12060054)
• Hypertrophic maturation of chondrocytes in induced by the TGF-beta type I receptors. (PMID:12082094)
• CD44 interaction with the TGF-betaRI kinase promotes activation of multiple signaling pathways required for ankyrin-membrane interaction, tumor cell migration, and oncogenic events during HA and TGF-beta-mediated metastatic breast tumor progression (PMID:12145287)
• elucidation of smad requirement in transforming growth factor-beta type I receptor-induced responses (PMID:12446693)
• TGF-beta1 receptor expression in peritoneal fibroblasts was increased by hypoxia or hypoxia plus TGF-beta1, but decreased by TGF-beta1 alone. (PMID:12607775)
• a C-to-T single-nucleotide polymorphism (C-509T) in the TGF-beta1 gene promoter may be associated with altered gene expression and asthma phenotype (PMID:14597484)
• 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)
• Blocking Smad7 expression by RNA interference inhibits association of GADD34-PP1c complex with TbetaRI. (PMID:14718519)
• 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)
• that an increased TGFbetaRI:TGFbetaRII ratio may underlie aberrant TGFbeta signaling in SSc and contribute to elevated basal collagen production (PMID:15146427)
• transforming growth factor-beta signaling has a role in receptor RI induction by histone deacetylase activity inhibition in breast cancer cells (PMID:15155736)
• endogenous IGFBP-3 directly inhibits proliferation of human intestinal smooth muscle cells by activation of TGF-betaRI and Smad2, an effect that is independent of its effect on IGF-I-stimulated growth. (PMID:15178549)
• sphingosine 1-phosphate receptors and the transforming growth factor beta-type I receptor serine/threonine kinase are essential for activation of Smad3 by lysophospholipids (PMID:15247277)
• Mutation in the TGFBR1 gene is associated with carcinomas of the kidney and bladder (PMID:15382067)
• Dpr2 binds to the TGFbeta receptors ALK5 and ALK4, and accelerates lysosomal degradation of these receptors (PMID:15459392)
• NEDD4-2 functions like Smurfs 1 and 2 in that it associates with TGF-beta type I receptor via Smad7, and induces its ubiquitin-dependent degradation (PMID:15496141)
• Bikunin neither decreased expression of TGF-beta receptors (TbetaRI and TbetaRII) in cancer cells nor altered the specific binding of 125I TGF-beta1 to the cells. (PMID:15498571)
• TGF-beta induces biglycan expression through ALK5 and GADD45beta (PMID:15546867)
• Genetic alterations reflecting mismatch repair of TGFBR1 gene do not occur in small bowel carcinoid tumors. (PMID:15599934)
• IL-6 increases trafficking of TGF-beta1 receptors to non-lipid raft-associated pools resulting in augmented TGF-beta1 Smad signaling (PMID:15661740)
• possible role of heterozygous mutation in a newly described human phenotype that includes widespread perturbations in cardiovascular, craniofacial, neurocognitive and skeletal development (PMID:15731757)
• The high expressions of TGF-beta1 and TGFbR1 play important roles in spontaneous abortion. (PMID:15938776)
• the Int7G24A variant of the TGFBR1 gene predisposes to small cell lung cancer risk (meta-analysis) (PMID:15955593)
• Pituitary cells, which demonstrate reduced expression of dopamine beta2 receptor, also show reduction of TGFbeta1 type I receptor. (PMID:15961557)
• reports the first molecular analysis of MSSE tumours showing loss of heterozygosity of the MSSE region, with loss of the normal allele, providing the first evidence that MSSE is a tumour suppressor gene (PMID:16170343)
• TGFbeta1/ALK5 may alleviate scarring in chronic fibrotic disease. (PMID:16314481)
• HCV NS5A modulates TGF-beta signaling through interaction with TbetaR-I (PMID:16407286)
• Int7G24A variant of transforming growth factor-beta receptor type I is associated with invasive breast cancer (PMID:16428477)
• Results of this analysis appear to exclude a role for the TGFBR1- or TGFBR2-mediated pathway effect in Kabuki syndrome. (PMID:16528739)
• ALK5 plays unique, non-redundant cell-autonomous roles during facial development in K14-Cre transgenic mice. (PMID:16806156)
• A comprehensive genetic analysis of TGFBR1 was performed in patients with Marfan syndrome or Marfan-related phenotypes. (PMID:16835936)
• TGF-beta type I receptor kinase has a role in progression of growth and metastasis of mouse mammary carcinoma (PMID:16857807)
• Mutations in either TGFBR1 or TGFBR2 predispose patients to aggressive and widespread vascular disease (Loeys-Dietz syndrome) (PMID:16928994)
• The majority of systemic sclerosis (SSc) fibroblasts exhibit elevated levels of transforming growth factor beta type I receptor (TGFbetaRI). (PMID:16947635)
• Synthesis of TGFbeta-1 and type I TGFbeta-receptor increases over time in recipients developing chronic allograft nephropathy. (PMID:16980081)
• The mRNA expressions of TGFbeta receptor type I (TGFbetaRI) in hMSCs increased with the length of cell culture. (PMID:16998703)
• Enhances tumor invasion and angiogenesis by stimulating expression of matrix metalloproteinase MMP-9. (PMID:17072348)
• The expression of TGFbetaR I and TGFbetaR II protein in nasal polyps tissues was significant increased than that in chronic rhinosinusitis tissues. (PMID:17087113)
• Epac1 inhibits TGFbeta-dependent regulation of cell migration and adhesion through TbetaRI (PMID:17203972)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tgfbr1a	ENSDARG00000017494
danio_rerio	tgfbr1b	ENSDARG00000042259
mus_musculus	Tgfbr1	ENSMUSG00000007613
rattus_norvegicus	Tgfbr1	ENSRNOG00000007036

Paralogs (11): BMPR1A (ENSG00000107779), ACVR2B (ENSG00000114739), ACVR1 (ENSG00000115170), ACVR2A (ENSG00000121989), ACVR1C (ENSG00000123612), AMHR2 (ENSG00000135409), ACVR1B (ENSG00000135503), BMPR1B (ENSG00000138696), ACVRL1 (ENSG00000139567), TGFBR2 (ENSG00000163513), BMPR2 (ENSG00000204217)

Protein

Protein identifiers

TGF-beta receptor type-1 — P36897 (reviewed: P36897)

Alternative names: Activin A receptor type II-like protein kinase of 53kD, Activin receptor-like kinase 5, Serine/threonine-protein kinase receptor R4, TGF-beta type I receptor, Transforming growth factor-beta receptor type I

All UniProt accessions (15): P36897, A0A8V8TMI6, A0AAQ5BHT0, A0AAQ5BHT5, A0AAQ5BHW0, A0AAQ5BHY0, A0AAQ5BHY8, A0AAQ5BHZ0, A0AAQ5BI21, B4DY26, F8VRH6, F8VXZ5, F8W0K6, F8W1R9, Q5T7S2

UniProt curated annotations — full annotation on UniProt →

Function. Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, 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 is thus regulating 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 the 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. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation.

Subunit / interactions. Homodimer; in the endoplasmic reticulum but also at the cell membrane. 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 TGBRB1 and TGFBR2 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 CD109; inhibits TGF-beta receptor activation in keratinocytes. Interacts with RBPMS. Interacts (unphosphorylated) with FKBP1A; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation. Interacts with SMAD2, SMAD3 and ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF-beta receptor. Interacts with TRAF6 and MAP3K7; induces MAP3K7 activation by TRAF6. Interacts with PARD6A; involved in TGF-beta induced epithelial to mesenchymal transition. Interacts with NEDD4L. Interacts with SMAD7, SMURF1 and SMURF2; SMAD7 recruits NEDD4L, SMURF1 and SMURF2 to the TGF-beta receptor. Interacts with USP15 and VPS39. Interacts with SDCBP (via C-terminus). Interacts with CAV1 and this interaction is impaired in the presence of SDCBP. Interacts with APPL1; interaction is TGF beta dependent; mediates trafficking of the TGFBR1 from the endosomes to the nucleus via microtubules in a TRAF6-dependent manner. Interacts with GPR50; this interaction promotes the constitutive activation of SMAD signaling pathway.

Subcellular location. Cell membrane. Cell junction. Tight junction. Cell surface. Membrane raft.

Tissue specificity. Found in all tissues examined, most abundant in placenta and least abundant in brain and heart. Expressed in a variety of cancer cell lines.

Post-translational modifications. Phosphorylated at basal levels in the absence of ligand. Activated upon phosphorylation by TGFBR2, mainly in the GS domain. Phosphorylation in the GS domain abrogates FKBP1A-binding. N-Glycosylated. Ubiquitinated; undergoes ubiquitination catalyzed by several E3 ubiquitin ligases including SMURF1, SMURF2 and NEDD4L2. Results in the proteasomal and/or lysosomal degradation of the receptor thereby negatively regulating its activity. Deubiquitinated by USP15, leading to stabilization of the protein and enhanced TGF-beta signal. Its ubiquitination and proteasome-mediated degradation is negatively regulated by SDCBP. Ubiquitinated by BFAR via’Lys-63’-linked ubiquitination at Lys-268, leading to TGF-beta signaling activation.

Disease relevance. Loeys-Dietz syndrome 1 (LDS1) [MIM:609192] 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. TGFBR1 mutation Gln-487 has been reported to be associated with thoracic aortic aneurysms and dissection (TAAD). This phenotype, also known as thoracic aortic aneurysms type 5 (AAT5), is distinguised from LDS1 by having aneurysms restricted to thoracic aorta. It is unclear, however, if this condition is fulfilled in individuals bearing Gln-487 mutation, that is why they are considered as LDS1 by the OMIM resource. Multiple self-healing squamous epithelioma (MSSE) [MIM:132800] A disorder characterized by multiple skin tumors that undergo spontaneous regression. Tumors appear most often on sun-exposed regions, are locally invasive, and undergo spontaneous resolution over a period of months leaving pitted scars. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Kept in an inactive conformation by FKBP1A preventing receptor activation in absence of ligand. CD109 is another inhibitor of the receptor.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P36897-1	1	yes
P36897-2	2, B
P36897-3	3

RefSeq proteins (24): NP_001124388, NP_001293139, NP_001394345, NP_001394346, NP_001394347, NP_001394348, NP_001394349, NP_001394351, NP_001394352, NP_001394353, NP_001394354, NP_001394355, NP_001394356, NP_001394357, NP_001394358, NP_001394359, NP_001394361, NP_001394362, NP_001394363, NP_001394364, NP_001394365, NP_001394366, NP_001394367, NP_004603* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000333	TGFB_receptor	Family
IPR000472	Activin_recp	Domain
IPR000719	Prot_kinase_dom	Domain
IPR003605	GS_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR045860	Snake_toxin-like_sf	Homologous_superfamily

Pfam: PF00069, PF01064, PF08515

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)
• EC 2.7.11.30 — receptor protein serine/threonine kinase (BRENDA: 8 organisms, 67 substrates, 81 inhibitors, 4 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. 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
ATP	0.0057–0.0088	2
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
KKVLTQMGSPSIRCS(P)SVS	0.26	1
KVLTQMGSPSVRCS(P)SMS	0.331	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 (105 total): strand 24, sequence variant 21, helix 18, mutagenesis site 11, modified residue 6, disulfide bond 5, turn 4, binding site 2, topological domain 2, cross-link 2, splice variant 2, domain 2, signal peptide 1, chain 1, glycosylation site 1, transmembrane region 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

44 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9J9D	X-RAY DIFFRACTION	1.34
8YHF	X-RAY DIFFRACTION	1.4
5E8S	X-RAY DIFFRACTION	1.45
5E8X	X-RAY DIFFRACTION	1.45
8YHL	X-RAY DIFFRACTION	1.47
4X2F	X-RAY DIFFRACTION	1.49
4X2G	X-RAY DIFFRACTION	1.51
5E8Z	X-RAY DIFFRACTION	1.51
5QIK	X-RAY DIFFRACTION	1.58
6B8Y	X-RAY DIFFRACTION	1.65
5QU0	X-RAY DIFFRACTION	1.67
4X0M	X-RAY DIFFRACTION	1.68
4X2J	X-RAY DIFFRACTION	1.69
4X2K	X-RAY DIFFRACTION	1.69
3HMM	X-RAY DIFFRACTION	1.7
3TZM	X-RAY DIFFRACTION	1.7
5E8T	X-RAY DIFFRACTION	1.7
5QIM	X-RAY DIFFRACTION	1.75
3GXL	X-RAY DIFFRACTION	1.8
4X2N	X-RAY DIFFRACTION	1.8
5QTZ	X-RAY DIFFRACTION	1.83
2WOT	X-RAY DIFFRACTION	1.85
5E8W	X-RAY DIFFRACTION	1.86
5QIL	X-RAY DIFFRACTION	1.98
1VJY	X-RAY DIFFRACTION	2
5FRI	X-RAY DIFFRACTION	2
5E8U	X-RAY DIFFRACTION	2.03
5E90	X-RAY DIFFRACTION	2.05
1PY5	X-RAY DIFFRACTION	2.3
2WOU	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P36897-F1	85.06	0.63

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): 333 (proton acceptor)

Ligand- & substrate-binding residues (2): 232; 211–219

Post-translational modifications (8): 165, 185, 186, 187, 189, 191, 268, 391

Disulfide bonds (5): 36–54, 38–41, 48–71, 86–100, 101–106

Glycosylation sites (1): 45

Mutagenesis-validated functional residues (11):

Position	Phenotype
185–186	loss of phosphorylation on threonine residues. loss of threonine phosphorylation, reduced phosphorylation on serine resi
187	loss of threonine phosphorylation, reduced phosphorylation on serine residues and loss of response to tgf-beta; when ass
189	loss of threonine phosphorylation, reduced phosphorylation on serine residues and loss of response to tgf-beta; when ass
191	loss of threonine phosphorylation, reduced phosphorylation on serine residues and loss of response to tgf-beta; when ass
193	loss of interaction with fkbp1a.
194	loss of interaction with fkbp1a.
200	loss of response to tgf-beta.
200	loss of phosphorylation. loss of response to tgf-beta.
204	constitutive activation.
204	reduced phosphorylation. reduced response to tgf-beta.
268	abolished its tcr-induced ubiquitination.

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-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-5689880	Ub-specific processing proteases
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: 895 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GGGACCA_MIR133A_MIR133B, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, GOBP_VENTRICULAR_SEPTUM_MORPHOGENESIS, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_CORONARY_VASCULATURE_DEVELOPMENT, GOBP_CARTILAGE_DEVELOPMENT, GOBP_HEART_TRABECULA_MORPHOGENESIS

GO Biological Process (86): skeletal system development (GO:0001501), in utero embryonic development (GO:0001701), kidney development (GO:0001822), blastocyst development (GO:0001824), epithelial to mesenchymal transition (GO:0001837), negative regulation of endothelial cell proliferation (GO:0001937), positive regulation of endothelial cell proliferation (GO:0001938), lens development in camera-type eye (GO:0002088), ventricular trabecula myocardium morphogenesis (GO:0003222), ventricular compact myocardium morphogenesis (GO:0003223), regulation of DNA-templated transcription (GO:0006355), apoptotic process (GO:0006915), signal transduction (GO:0007165), transforming growth factor beta receptor signaling pathway (GO:0007179), nervous system development (GO:0007399), heart development (GO:0007507), positive regulation of cell population proliferation (GO:0008284), primordial germ cell migration (GO:0008354), male gonad development (GO:0008584), post-embryonic development (GO:0009791), anterior/posterior pattern specification (GO:0009952), regulation of gene expression (GO:0010468), positive regulation of gene expression (GO:0010628), regulation of epithelial to mesenchymal transition (GO:0010717), positive regulation of epithelial to mesenchymal transition (GO:0010718), peptidyl-serine phosphorylation (GO:0018105), collagen fibril organization (GO:0030199), positive regulation of cell growth (GO:0030307), positive regulation of cell migration (GO:0030335), negative regulation of cell migration (GO:0030336), regulation of protein ubiquitination (GO:0031396), negative regulation of chondrocyte differentiation (GO:0032331), activin receptor signaling pathway (GO:0032924), intracellular signal transduction (GO:0035556), myofibroblast differentiation (GO:0036446), wound healing (GO:0042060), endothelial cell activation (GO:0042118), extracellular structure organization (GO:0043062), endothelial cell migration (GO:0043542), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (20): protein kinase activity (GO:0004672), 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 I (GO:0005025), type II transforming growth factor beta receptor binding (GO:0005114), ATP binding (GO:0005524), activin receptor activity, type I (GO:0016361), ubiquitin protein ligase binding (GO:0031625), SMAD binding (GO:0046332), metal ion binding (GO:0046872), activin binding (GO:0048185), transforming growth factor beta binding (GO:0050431), I-SMAD binding (GO:0070411), nucleotide binding (GO:0000166), signaling receptor binding (GO:0005102), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), growth factor binding (GO:0019838)

GO Cellular Component (15): nucleus (GO:0005634), nucleoplasm (GO:0005654), endosome (GO:0005768), plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), cilium (GO:0005929), cell surface (GO:0009986), membrane (GO:0016020), signaling receptor complex (GO:0043235), membrane raft (GO:0045121), activin receptor complex (GO:0048179), transforming growth factor beta ligand-receptor complex (GO:0070021), ciliary tip (GO:0097542), anchoring junction (GO:0070161), serine/threonine protein kinase complex (GO:1902554)

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 TGFBR1 in Cancer	2
Deubiquitination	2
TGF-beta receptor signaling activates SMADs	1
Loss of Function of SMAD2/3 in Cancer	1
Loss of Function of TGFBR2 in Cancer	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
protein binding	3
system development	2
animal organ development	2
anatomical structure development	2
endothelial cell proliferation	2
regulation of endothelial cell proliferation	2
ventricular cardiac muscle tissue morphogenesis	2
plasma membrane signaling receptor complex	2
serine/threonine protein kinase complex	2
chordate embryonic development	1
renal system development	1
in utero embryonic development	1
mesenchymal cell differentiation	1
negative regulation of epithelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
camera-type eye development	1
heart trabecula morphogenesis	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
circulatory system development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
gamete generation	1
cell migration	1
gonad development	1
development of primary male sexual characteristics	1
multicellular organism development	1

Protein interactions and networks

STRING

4270 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TGFBR1	TGFB1	P01137	999
TGFBR1	SMAD7	O15105	998
TGFBR1	SMAD2	Q15796	998
TGFBR1	TGFB3	P10600	997
TGFBR1	TGFB2	P08112	997
TGFBR1	SMAD3	P84022	994
TGFBR1	MSTN	O14793	991
TGFBR1	FKBP1A	P20071	988
TGFBR1	ACVR2B	Q13705	986
TGFBR1	TGFBR2	P37173	986
TGFBR1	GDF11	O95390	977
TGFBR1	TGFBR3	Q03167	976
TGFBR1	SMAD4	Q13485	975
TGFBR1	ACVR1B	P36896	975
TGFBR1	TRAF6	Q9Y4K3	965

IntAct

127 interactions, top by confidence:

A	B	Type	Score
	TGFBR1	psi-mi:“MI:0403”(colocalization)	0.650
TGFBR1		psi-mi:“MI:2364”(proximity)	0.650
TGFBR1		psi-mi:“MI:0407”(direct interaction)	0.650
	TGFBR1	psi-mi:“MI:0407”(direct interaction)	0.650
TGFBR1		psi-mi:“MI:0915”(physical association)	0.650
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
TGFB3	TGFBR1	psi-mi:“MI:0915”(physical association)	0.630
TGFBR1	FKBP1A	psi-mi:“MI:0407”(direct interaction)	0.590
TGFBR1	FKBP1A	psi-mi:“MI:0915”(physical association)	0.590
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
YWHAZ	TGFBR1	psi-mi:“MI:0915”(physical association)	0.560
TGFBR1	YWHAZ	psi-mi:“MI:0403”(colocalization)	0.560
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
EVA1C	STK25	psi-mi:“MI:0914”(association)	0.530
HFE	ADAM10	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
TGFB1	TGFBR1	psi-mi:“MI:0407”(direct interaction)	0.440
TGFBR1	TGFB1	psi-mi:“MI:0407”(direct interaction)	0.440
TGFBR1	NLGN3	psi-mi:“MI:0915”(physical association)	0.400
LRG1	TGFBR1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (431): TGFBR1 (Affinity Capture-Western), PSEN1 (Affinity Capture-Western), NOTCH1 (Affinity Capture-Western), TGFBR1 (Affinity Capture-Western), TGFBR1 (Co-localization), Nkiras1 (Affinity Capture-Luminescence), Rasd2 (Affinity Capture-Luminescence), Rab13 (Affinity Capture-Luminescence), Rab33b (Affinity Capture-Luminescence), Rhebl1 (Affinity Capture-Luminescence), Rab6b (Affinity Capture-Luminescence), Rhod (Affinity Capture-Luminescence), Rab3b (Affinity Capture-Luminescence), Rab38 (Affinity Capture-Luminescence), Rhobtb1 (Affinity Capture-Luminescence)

ESM2 similar proteins: O00238, O08680, O42127, O42422, O46680, O73875, P09759, P22182, P29318, P29319, P29320, P29323, P36894, P36895, P36896, P36897, P36898, P37023, P37172, P54755, P54756, P54757, P54758, P54759, P54762, P70539, P80201, P80202, P80203, P80204, Q04771, Q05438, Q09488, Q15375, Q28041, Q5CD18, Q5RAN0, Q60629, Q61271, Q61288

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

65 interactions.

A	Effect	B	Mechanism
SMURF2	“down-regulates activity”	TGFBR1	ubiquitination
PPP1CC	down-regulates	TGFBR1	dephosphorylation
“SB 505124”	down-regulates	TGFBR1	“chemical inhibition”
WWP1	down-regulates	TGFBR1	ubiquitination
UCHL5	“up-regulates quantity by stabilization”	TGFBR1	binding
DACT2	down-regulates	TGFBR1	binding
SMURF1	“down-regulates activity”	TGFBR1	ubiquitination
LY-2157299	down-regulates	TGFBR1	“chemical inhibition”
452342-67-5	down-regulates	TGFBR1	“chemical inhibition”
SMAD6	“down-regulates activity”	TGFBR1	binding
SMAD7	“down-regulates activity”	TGFBR1	binding
TGFBR1	down-regulates	EEF1A1	phosphorylation
HSP90AA1	up-regulates	TGFBR1	binding
TGFB1	“up-regulates activity”	TGFBR1	binding
TGFB2	up-regulates	TGFBR1	binding
TGFBR1	unknown	TP63	phosphorylation
“SB 431542”	down-regulates	TGFBR1	“chemical inhibition”
6-[2-tert-butyl-5-(6-methyl-2-pyridinyl)-1H-imidazol-4-yl]quinoxaline	down-regulates	TGFBR1	“chemical inhibition”
TGFBR1	“up-regulates activity”	RAC1
TGFBR1	“up-regulates activity”	RHOA
PPP2R2A	up-regulates	TGFBR1	binding
TGFBR1	up-regulates	PIK3R1	binding
TGFBR1	up-regulates	PIK3R2	binding
TGFBR1	“up-regulates activity”	TRAF6	binding
FKBP1A	“down-regulates activity”	TGFBR1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 139 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
TGF-beta receptor signaling activates SMADs	6	24.5×	2e-05
Signaling by TGFB family members	9	13.0×	1e-05
Signaling by TGF-beta Receptor Complex	5	12.5×	1e-03
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	9	9.8×	3e-05
SLC-mediated transmembrane transport	7	5.2×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
activin receptor signaling pathway	6	51.2×	6e-07
positive regulation of SMAD protein signal transduction	8	29.5×	2e-07
positive regulation of epithelial to mesenchymal transition	6	18.3×	3e-04
cellular response to growth factor stimulus	5	15.3×	2e-03
transmembrane transport	7	11.3×	7e-04
transforming growth factor beta receptor signaling pathway	7	10.7×	8e-04
BMP signaling pathway	5	9.7×	8e-03
cell surface receptor signaling pathway	10	6.2×	9e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — ESCA.

Clinical variants and AI predictions

ClinVar

1192 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	53
Likely pathogenic	53
Uncertain significance	605
Likely benign	315
Benign	34

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068551	NM_004612.4(TGFBR1):c.1005A>T (p.Lys335Asn)	Pathogenic
12520	NM_004612.4(TGFBR1):c.953T>G (p.Met318Arg)	Pathogenic
12521	NM_004612.4(TGFBR1):c.1199A>G (p.Asp400Gly)	Pathogenic
12522	NM_004612.4(TGFBR1):c.599C>T (p.Thr200Ile)	Pathogenic
12523	NM_004612.4(TGFBR1):c.1460G>C (p.Arg487Pro)	Pathogenic
12525	NM_004612.4(TGFBR1):c.1460G>A (p.Arg487Gln)	Pathogenic
1310495	NM_004612.4(TGFBR1):c.1126A>G (p.Lys376Glu)	Pathogenic
1327810	NM_004612.4(TGFBR1):c.974-1G>A	Pathogenic
1445913	NM_004612.4(TGFBR1):c.102dup (p.Gln35fs)	Pathogenic
1451312	NM_004612.4(TGFBR1):c.516dup (p.Glu173fs)	Pathogenic
1771606	NM_004612.4(TGFBR1):c.1395_1396dup (p.Val466fs)	Pathogenic
180539	NM_004612.4(TGFBR1):c.1444A>G (p.Arg482Gly)	Pathogenic
1805979	NM_004612.4(TGFBR1):c.98-1G>A	Pathogenic
1972500	NM_004612.4(TGFBR1):c.694A>T (p.Lys232Ter)	Pathogenic
2073964	NM_004612.4(TGFBR1):c.715G>A (p.Glu239Lys)	Pathogenic
2089288	NM_004612.4(TGFBR1):c.706T>C (p.Ser236Pro)	Pathogenic
2114646	NM_004612.4(TGFBR1):c.836T>C (p.Val279Ala)	Pathogenic
213896	NM_004612.4(TGFBR1):c.680AAG[1] (p.Glu228del)	Pathogenic
2425183	NC_000009.11:g.(?101867488)(101867604_?)del	Pathogenic
263391	NM_004612.4(TGFBR1):c.71_75del (p.Ala24fs)	Pathogenic
263856	NM_004612.4(TGFBR1):c.1302_1303dup (p.Asp435fs)	Pathogenic
2704960	NM_004612.4(TGFBR1):c.1083del (p.Thr362fs)	Pathogenic
2718378	NM_004612.4(TGFBR1):c.973+1G>T	Pathogenic
2735307	NM_004612.4(TGFBR1):c.238C>T (p.Arg80Ter)	Pathogenic
2748941	NM_004612.4(TGFBR1):c.3_27dup (p.Pro10fs)	Pathogenic
2820205	NM_004612.4(TGFBR1):c.1391dup (p.Leu464fs)	Pathogenic
2836884	NM_004612.4(TGFBR1):c.236_237insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCTGAGGCAGAATGATCACCTGAGGTCAGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAGAAATTGACTTAATTCC (p.Pro79_Arg80insAlaGlyArgGlyGlySerArgLeuTer)	Pathogenic
2861761	NM_004612.4(TGFBR1):c.686T>C (p.Val229Ala)	Pathogenic
2919536	NM_004612.4(TGFBR1):c.1189A>T (p.Lys397Ter)	Pathogenic
2972640	NM_004612.4(TGFBR1):c.1043G>A (p.Cys348Tyr)	Pathogenic

SpliceAI

2328 predictions. Top by Δscore:

Variant	Effect	Δscore
9:99132685:GGTAC:G	donor_gain	1.0000
9:99137854:TTTA:T	acceptor_loss	1.0000
9:99144730:A:AG	acceptor_gain	1.0000
9:99144731:G:GA	acceptor_gain	1.0000
9:99144731:G:GT	acceptor_loss	1.0000
9:99144731:GGAA:G	acceptor_gain	1.0000
9:99144731:GGAAA:G	acceptor_gain	1.0000
9:99144824:G:GG	donor_gain	1.0000
9:99144886:AAGG:A	donor_loss	1.0000
9:99144887:AGGT:A	donor_loss	1.0000
9:99144888:GGTAT:G	donor_loss	1.0000
9:99144889:G:C	donor_loss	1.0000
9:99144890:T:A	donor_loss	1.0000
9:99146567:GGC:G	donor_gain	1.0000
9:99147642:A:AG	acceptor_gain	1.0000
9:99147642:AAACT:A	acceptor_gain	1.0000
9:99147643:A:G	acceptor_gain	1.0000
9:99147643:AACT:A	acceptor_gain	1.0000
9:99147644:A:AG	acceptor_gain	1.0000
9:99147644:ACT:A	acceptor_gain	1.0000
9:99147645:C:G	acceptor_gain	1.0000
9:99147646:T:TA	acceptor_gain	1.0000
9:99147649:TACAG:T	acceptor_loss	1.0000
9:99147651:CAGGA:C	acceptor_loss	1.0000
9:99147652:A:AG	acceptor_gain	1.0000
9:99147653:G:GC	acceptor_loss	1.0000
9:99147653:G:GG	acceptor_gain	1.0000
9:99147653:GGA:G	acceptor_gain	1.0000
9:99147780:GTGAA:G	donor_gain	1.0000
9:99147781:TGAA:T	donor_gain	1.0000

AlphaMissense

3269 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:99128901:T:G	C48W	1.000
9:99128911:G:T	G52W	1.000
9:99128917:T:A	C54S	1.000
9:99128917:T:C	C54R	1.000
9:99128918:G:A	C54Y	1.000
9:99128918:G:C	C54S	1.000
9:99128919:C:G	C54W	1.000
9:99128968:T:A	C71S	1.000
9:99128968:T:C	C71R	1.000
9:99128969:G:A	C71Y	1.000
9:99128969:G:C	C71S	1.000
9:99128970:T:G	C71W	1.000
9:99129013:T:A	C86S	1.000
9:99129013:T:C	C86R	1.000
9:99129014:G:A	C86Y	1.000
9:99129014:G:C	C86S	1.000
9:99129055:T:A	C100S	1.000
9:99129056:G:C	C100S	1.000
9:99129057:C:G	C100W	1.000
9:99129073:T:A	C106S	1.000
9:99129074:G:C	C106S	1.000
9:99132557:C:A	A131D	1.000
9:99132727:G:C	G188R	1.000
9:99132728:G:A	G188D	1.000
9:99132733:G:C	G190R	1.000
9:99132734:G:A	G190D	1.000
9:99132739:G:C	G192R	1.000
9:99137859:G:A	G192D	1.000
9:99137871:T:C	L196P	1.000
9:99137883:C:T	T200I	1.000

dbSNP variants (sampled 300 via entrez): RS1000041498 (9:99112492 T>C,G), RS1000051881 (9:99103309 T>C), RS1000163498 (9:99109536 T>C), RS1000196067 (9:99140313 G>A), RS1000272031 (9:99142230 T>C,G), RS1000318050 (9:99106279 G>A), RS1000319748 (9:99149639 C>A,T), RS1000447764 (9:99143492 A>G), RS1000453834 (9:99106497 G>A), RS1000491777 (9:99148066 C>T), RS1000565460 (9:99137089 A>G), RS1000596540 (9:99136744 A>C,T), RS1000657915 (9:99102772 T>C,G), RS1000667958 (9:99124214 T>A), RS1000741153 (9:99123893 G>A)

Disease associations

OMIM: gene MIM:190181 | disease phenotypes: MIM:607086, MIM:132800, MIM:609192, MIM:154700, MIM:130000, MIM:123100, MIM:169300, MIM:611788

GenCC curated gene-disease

Disease	Classification	Inheritance
multiple self-healing squamous epithelioma	Definitive	Autosomal dominant
Loeys-Dietz syndrome 1	Definitive	Autosomal dominant
Loeys-Dietz syndrome	Supportive	Autosomal dominant
familial thoracic aortic aneurysm and aortic dissection	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
multiple self-healing squamous epithelioma	Definitive	AD
Loeys-Dietz syndrome	Definitive	AD

Mondo (14): familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625), multiple self-healing squamous epithelioma (MONDO:0007566), Loeys-Dietz syndrome 1 (MONDO:0012212), Loeys-Dietz syndrome (MONDO:0018954), Marfan syndrome (MONDO:0007947), Ehlers-Danlos syndrome (MONDO:0020066), thoracic aortic aneurysm (MONDO:0005396), myoepithelial tumor (MONDO:0002380), craniosynostosis (MONDO:0015469), aortic aneurysm (MONDO:0005160), pectus excavatum (MONDO:0008213), connective tissue disorder (MONDO:0003900), aortic aneurysm, familial thoracic 6 (MONDO:0012730), Ehlers-Danlos syndrome, classic type (MONDO:0007522)

Orphanet (9): Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387), Loeys-Dietz syndrome (Orphanet:60030), Multiple self-healing squamous epithelioma (Orphanet:65748), Marfan syndrome type 1 (Orphanet:284963), Marfan syndrome (Orphanet:558), Ehlers-Danlos syndrome (Orphanet:98249), Craniosynostosis (Orphanet:1531), Classical Ehlers-Danlos syndrome (Orphanet:287), Furlong syndrome (Orphanet:97295)

HPO phenotypes

109 total (30 of 109 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:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000272	Malar flattening
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000324	Facial asymmetry
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000411	Protruding ear
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000525	Abnormality iris morphology
HP:0000545	Myopia
HP:0000577	Exotropia
HP:0000592	Blue sclerae
HP:0000766	Abnormal sternum morphology
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000822	Hypertension
HP:0000963	Thin skin
HP:0000964	Eczematoid dermatitis
HP:0000965	Cutis marmorata

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001713_32	Dental caries	5.000000e-06
GCST001884_19	Age-related macular degeneration	3.000000e-11
GCST002092_1	Callous-unemotional behaviour	3.000000e-06
GCST002576_4	Epithelial ovarian cancer	2.000000e-08
GCST003219_28	Advanced age-related macular degeneration	4.000000e-10
GCST004049_2	Cough in response to angiotensin-converting enzyme inhibitor drugs	2.000000e-06
GCST004899_5	Gestational age at birth (maternal effect)	5.000000e-07
GCST006291_87	Spherical equivalent or myopia (age of diagnosis)	2.000000e-09
GCST009798_9	Asthma	2.000000e-10
GCST010002_275	Refractive error	7.000000e-25
GCST010042_42	Asthma	1.000000e-13
GCST010516_5	Fractures (paediatric)	1.000000e-06
GCST90014325_15	Asthma	6.000000e-12

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005322	callous-unemotional behaviour
EFO:1001492	atrophic macular degeneration
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0005112	gestational age
EFO:0005939	parental genotype effect measurement
EFO:0004847	age at onset

MeSH disease descriptors (11)

Descriptor	Name	Tree numbers
D001014	Aortic Aneurysm	C14.907.055.239; C14.907.109.139
D017545	Aortic Aneurysm, Thoracic	C14.907.055.239.125; C14.907.109.139.125
D003240	Connective Tissue Diseases	C17.300
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
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
D005660	Funnel Chest	C05.116.099.386; C05.660.386; C16.131.621.386
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
D009208	Myoepithelioma	C04.557.435.585
C567085	Aortic Aneurysm, Familial Thoracic 6 (supp.)
C536150	Keratoacanthoma familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4439 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

28 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 76,984 (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
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL5416410	DASATINIB	4	655
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL217092	SARACATINIB	3	3,982
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL3544983	TESEVATINIB	3	2,819
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL603469	LESTAURTINIB	3
CHEMBL2364611	GALUNISERTIB	2	1,929
CHEMBL253969	OSI-632	2	1,150
CHEMBL3120215	OSI-027	2	1,854
CHEMBL3260567	VACTOSERTIB	2	898
CHEMBL3545396	BMS-690514	2	567
CHEMBL402548	DANUSERTIB	2	1,928
CHEMBL475251	R-406	2	762
CHEMBL495727	AT-9283	2	1,376
CHEMBL5314579	ZILURGISERTIB	2	26
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL5956963	KER-047	2
CHEMBL1090479	GSK-1070916	1
CHEMBL3544932	TAK-901	1
CHEMBL3545085	XL-228	1
CHEMBL3600873	MK-5108	1
CHEMBL4594432	LY-3200882	1
CHEMBL482967	CYC-116	1
CHEMBL5095192	PF-06952229	1

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

GtoPdb / IUPHAR curated pharmacology

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

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

Most potent curated ligand interactions (17 total), top 17:

Ligand	Action	Affinity	Parameter
BMS-986260	Inhibition	8.8	pIC50
vactosertib	Inhibition	7.96	pIC50
tosposertib	Inhibition	7.94	pIC50
TGF-beta RI kinase inhibitor	Inhibition	7.57	pIC50
LY2109761	Inhibition	7.42	pKi
SD-208	Inhibition	7.28	pIC50
TGF-beta RI inhibitor III	Inhibition	7.27	pIC50
compound 13r [PMID: 23639540]	Inhibition	7.12	pIC50
compound 15b [PMID: 16539403]	Inhibition	7.1	pIC50
SB-431542	Inhibition	7.03	pIC50
ontunisertib	Inhibition	7.0	pIC50
galunisertib	Inhibition	6.76	pIC50
compound 13d [PMID: 23639540]	Inhibition	6.75	pIC50
H. polygyrus TGF-β mimic	Agonist	6.46	pKd
BIX02189	Inhibition	6.24	pIC50
LDN-214117	Inhibition	5.52	pIC50
zilurgisertib	Inhibition	5.2	pIC50

Binding affinities (BindingDB)

1260 measured of 1320 human assays (1320 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
29 N,N-Dimethyl-2-(4-(2-(6- methylpyridin-2-yl)-6,7-dihydro-5H- pyrrolo[1,2-a]imidazol-3-yl)pyridin-2- yl)-4,6-dihydropyrrolo[3,4-d]imidazol- 5(1H)-carboxamide	IC50	0.18 nM	US-20250179094: TGF-B INHIBITOR COMPOUND AND USE THEREOF
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
71 (2-(4-(2-(6-Methylpyridin-2-yl)-5,6- dihydro-4H-pyrrolo[1,2-b]pyrazol-3- yl)pyridin-2-yl)-4,6-dihydro- pyrrolo[3,4-d]imidazol-5(1H)- yl)(morpholinyl)ketone	IC50	0.67 nM	US-20250179094: TGF-B INHIBITOR COMPOUND AND USE THEREOF
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

ChEMBL bioactivities

4054 potent at pChembl≥5 of 4111 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.85	Ki	0.14	nM	CHEMBL4209835
9.85	Ki	0.14	nM	CHEMBL4210246
9.82	Ki	0.15	nM	CHEMBL4209583
9.72	IC50	0.19	nM	CHEMBL5962152
9.69	Ki	0.2042	nM	CHEMBL6152275
9.66	Ki	0.22	nM	CHEMBL4217699
9.60	IC50	0.25	nM	CHEMBL5776223
9.60	IC50	0.25	nM	CHEMBL5769608
9.60	IC50	0.25	nM	CHEMBL5864462
9.60	IC50	0.25	nM	CHEMBL5919249
9.59	IC50	0.26	nM	CHEMBL6011920
9.57	Kd	0.266	nM	CHEMBL3752910
9.57	IC50	0.27	nM	CHEMBL5821659
9.52	IC50	0.3	nM	CHEMBL5938382
9.52	IC50	0.3	nM	CHEMBL5861967
9.49	IC50	0.32	nM	CHEMBL4852453
9.48	Ki	0.33	nM	CHEMBL519948
9.47	IC50	0.34	nM	CHEMBL4858177
9.46	IC50	0.35	nM	CHEMBL4877947
9.43	IC50	0.37	nM	CHEMBL6001390
9.43	IC50	0.37	nM	CHEMBL5784295
9.42	ED50	0.384	nM	CHEMBL3752910
9.41	IC50	0.39	nM	CHEMBL5891826
9.40	IC50	0.4	nM	CHEMBL5908946
9.40	IC50	0.4	nM	CHEMBL5774806
9.40	IC50	0.4	nM	CHEMBL6060062
9.40	IC50	0.4	nM	CHEMBL5956002
9.40	IC50	0.4	nM	CHEMBL5972103
9.38	IC50	0.42	nM	CHEMBL5946698
9.35	Ki	0.4467	nM	CHEMBL6172040
9.34	IC50	0.46	nM	CHEMBL5860285
9.33	IC50	0.47	nM	CHEMBL5782584
9.31	IC50	0.49	nM	CHEMBL5823752
9.30	IC50	0.5	nM	CHEMBL6004077
9.30	IC50	0.5	nM	CHEMBL5921032
9.30	IC50	0.5	nM	CHEMBL5804130
9.29	IC50	0.51	nM	CHEMBL4846578
9.29	Ki	0.5129	nM	CHEMBL6170212
9.28	IC50	0.52	nM	CHEMBL5826016
9.28	IC50	0.53	nM	CHEMBL5995381
9.27	IC50	0.54	nM	CHEMBL4872884
9.26	IC50	0.55	nM	CHEMBL4217699
9.26	Ki	0.5495	nM	CHEMBL6167117
9.25	IC50	0.56	nM	CHEMBL4217699
9.24	IC50	0.58	nM	CHEMBL5982418
9.24	IC50	0.58	nM	CHEMBL5979440
9.24	IC50	0.57	nM	CHEMBL1835530
9.23	IC50	0.59	nM	CHEMBL5816769
9.23	IC50	0.59	nM	CHEMBL6034053
9.23	IC50	0.59	nM	CHEMBL5910145

PubChem BioAssay actives

1844 with measured affinity, of 3981 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
N-[4-[[2-[6-(trifluoromethyl)-2-pyridinyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-2-pyridinyl]acetamide	1374244: Inhibition of human His-tagged TGFbetaR1 T204D mutant expressed in Sf9 insect cells after 1 hr by HTRF assay	ki	0.0001	uM
N-(3-fluoro-4-pyridinyl)-2-(6-methyl-2-pyridinyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1374244: Inhibition of human His-tagged TGFbetaR1 T204D mutant expressed in Sf9 insect cells after 1 hr by HTRF assay	ki	0.0001	uM
N-(3-fluoro-4-pyridinyl)-2-(6-methyl-2-pyridinyl)-7H-purin-6-amine	1374244: Inhibition of human His-tagged TGFbetaR1 T204D mutant expressed in Sf9 insect cells after 1 hr by HTRF assay	ki	0.0001	uM
N-(3-fluoro-4-pyridinyl)-2-[6-(trifluoromethyl)-2-pyridinyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1374244: Inhibition of human His-tagged TGFbetaR1 T204D mutant expressed in Sf9 insect cells after 1 hr by HTRF assay	ki	0.0002	uM
7-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]-N-[2-(3-methylphenyl)-4-pyridinyl]quinolin-4-amine	1784532: Inhibition of human TGFbeta receptor 1 in human HEK293 cells preincubated for 24 hrs followed by addition of TGFbeta1 and measured after 24 hrs by luciferase based assay	ic50	0.0003	uM
7-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]-N-[2-(2-methylphenyl)-4-pyridinyl]quinolin-4-amine	1784532: Inhibition of human TGFbeta receptor 1 in human HEK293 cells preincubated for 24 hrs followed by addition of TGFbeta1 and measured after 24 hrs by luciferase based assay	ic50	0.0003	uM
7-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]-N-(2-phenyl-4-pyridinyl)quinolin-4-amine	1784532: Inhibition of human TGFbeta receptor 1 in human HEK293 cells preincubated for 24 hrs followed by addition of TGFbeta1 and measured after 24 hrs by luciferase based assay	ic50	0.0003	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149578: Binding affinity to human TGFBR1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0003	uM
4-(6-methyl-2-pyridinyl)-5-quinoxalin-6-yl-1,3-thiazol-2-amine	368190: Binding affinity to human TGFBR1	ki	0.0003	uM
7-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]-N-[2-(furan-3-yl)-4-pyridinyl]quinolin-4-amine	1784532: Inhibition of human TGFbeta receptor 1 in human HEK293 cells preincubated for 24 hrs followed by addition of TGFbeta1 and measured after 24 hrs by luciferase based assay	ic50	0.0005	uM
N-[2-(furan-3-yl)-4-pyridinyl]-7-(4-methylsulfonylphenyl)quinolin-4-amine	1784532: Inhibition of human TGFbeta receptor 1 in human HEK293 cells preincubated for 24 hrs followed by addition of TGFbeta1 and measured after 24 hrs by luciferase based assay	ic50	0.0005	uM
N-[2-(2,5-difluorophenyl)-4-pyridinyl]-7-(4-methylsulfonylphenyl)quinolin-4-amine	1784532: Inhibition of human TGFbeta receptor 1 in human HEK293 cells preincubated for 24 hrs followed by addition of TGFbeta1 and measured after 24 hrs by luciferase based assay	ic50	0.0006	uM
7-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]-N-[2-(3-fluorophenyl)-4-pyridinyl]quinolin-4-amine	1784532: Inhibition of human TGFbeta receptor 1 in human HEK293 cells preincubated for 24 hrs followed by addition of TGFbeta1 and measured after 24 hrs by luciferase based assay	ic50	0.0006	uM
N-[2-(2-methylphenyl)-4-pyridinyl]-7-(4-methylsulfonylphenyl)quinolin-4-amine	1784532: Inhibition of human TGFbeta receptor 1 in human HEK293 cells preincubated for 24 hrs followed by addition of TGFbeta1 and measured after 24 hrs by luciferase based assay	ic50	0.0006	uM
N-(4-methoxyphenyl)-3-(6-methyl-2-pyridinyl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazole-1-carbothioamide	622809: Inhibition of human recombinant GST-fused ALK5 expressed in Sf9 cells using casein as a substrate by radioisotopic protein kinase assay	ic50	0.0006	uM
6-[3-(2,2-difluoroethyl)-5-(6-methyl-2-pyridinyl)imidazol-4-yl]imidazo[1,2-a]pyridine-3-carboxamide	1542036: Inhibition of His-tagged TGFBR1 kinase domain T204D mutant (unknown origin) incubated for 1 hr by HTRF analysis	ic50	0.0007	uM
N-[2-(2-fluorophenyl)-4-pyridinyl]-7-(4-methylsulfonylphenyl)quinolin-4-amine	1784532: Inhibition of human TGFbeta receptor 1 in human HEK293 cells preincubated for 24 hrs followed by addition of TGFbeta1 and measured after 24 hrs by luciferase based assay	ic50	0.0007	uM
5-(5-fluoro-6-methyl-2-pyridinyl)-4-quinoxalin-6-yl-1H-imidazol-2-amine	368190: Binding affinity to human TGFBR1	ki	0.0007	uM
6-[5-(3-chloro-4-fluorophenyl)-3-(2-hydroxyethyl)imidazol-4-yl]imidazo[1,2-b]pyridazine-3-carbonitrile	1542087: Inhibition of TGFBR1 in human whole blood assessed as apparent inhibition constant by measuring reduction in TGFbeta-induced SMAD phosphorylation	ki	0.0008	uM
N-[2-(3-methylphenyl)-4-pyridinyl]-7-(4-methylsulfonylphenyl)quinolin-4-amine	1784532: Inhibition of human TGFbeta receptor 1 in human HEK293 cells preincubated for 24 hrs followed by addition of TGFbeta1 and measured after 24 hrs by luciferase based assay	ic50	0.0008	uM
7-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]-N-[2-(2-fluorophenyl)-4-pyridinyl]quinolin-4-amine	1784532: Inhibition of human TGFbeta receptor 1 in human HEK293 cells preincubated for 24 hrs followed by addition of TGFbeta1 and measured after 24 hrs by luciferase based assay	ic50	0.0008	uM
6-[3-(2,2-difluoroethyl)-5-(4-fluorophenyl)imidazol-4-yl]imidazo[1,2-b]pyridazine-3-carboxamide	1542036: Inhibition of His-tagged TGFBR1 kinase domain T204D mutant (unknown origin) incubated for 1 hr by HTRF analysis	ic50	0.0009	uM
7-(4-methylsulfonylphenyl)-N-(2-phenyl-4-pyridinyl)quinolin-4-amine	1784532: Inhibition of human TGFbeta receptor 1 in human HEK293 cells preincubated for 24 hrs followed by addition of TGFbeta1 and measured after 24 hrs by luciferase based assay	ic50	0.0009	uM
N-[4-[3-[6-(difluoromethyl)-2-pyridinyl]-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridinyl]acetamide	1423792: Inhibition of TGFbetaR1 T204D mutant (unknown origin) kinase domain after 1 hr by HTRF assay	ic50	0.0010	uM
6-[3-(2,2-difluoroethyl)-5-(6-methyl-2-pyridinyl)imidazol-4-yl]imidazo[1,2-a]pyridine	1542036: Inhibition of His-tagged TGFBR1 kinase domain T204D mutant (unknown origin) incubated for 1 hr by HTRF analysis	ic50	0.0010	uM
N-(3-fluoro-4-pyridinyl)-2-(6-methyl-2-pyridinyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine	1374244: Inhibition of human His-tagged TGFbetaR1 T204D mutant expressed in Sf9 insect cells after 1 hr by HTRF assay	ic50	0.0010	uM
3-[N-[4-[2-(dimethylamino)ethyl-methylsulfonylamino]phenyl]-C-phenylcarbonimidoyl]-N-ethyl-2-hydroxy-1H-indole-6-carboxamide	526941: Inhibition of TGFbeta receptor	ic50	0.0010	uM
6-[4-methyl-1-(6-methyl-2-pyridinyl)pyrazol-5-yl]-3H-quinazolin-4-one	658823: Inhibition of ALK5	ic50	0.0010	uM
N-[2-(2,5-difluorophenyl)-4-pyridinyl]-7-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]quinolin-4-amine	1784532: Inhibition of human TGFbeta receptor 1 in human HEK293 cells preincubated for 24 hrs followed by addition of TGFbeta1 and measured after 24 hrs by luciferase based assay	ic50	0.0010	uM
N-[2-(2,5-difluorophenyl)-5-methyl-4-pyridinyl]-1H-pyrazolo[4,3-b]pyridin-7-amine	1444757: Inhibition of recombinant N-terminal GST tagged human ALK5 (200 to 503 residues) expressed in baculovirus expression system using FAM-NH2-KVLTQMGSPSIRCSS[PO4]VS peptide as substrate after 90 mins by LanthaScreen TR-FRET assay	ic50	0.0010	uM
7-[[2-(2,5-difluorophenyl)-5-methyl-4-pyridinyl]amino]-N-methylpyrazolo[4,3-b]pyridine-1-carboxamide	1444757: Inhibition of recombinant N-terminal GST tagged human ALK5 (200 to 503 residues) expressed in baculovirus expression system using FAM-NH2-KVLTQMGSPSIRCSS[PO4]VS peptide as substrate after 90 mins by LanthaScreen TR-FRET assay	ic50	0.0010	uM
6-[3-ethyl-1-(6-methyl-2-pyridinyl)pyrazol-5-yl]-3-methylquinazolin-4-one	658823: Inhibition of ALK5	ic50	0.0010	uM
N-[4-[[2-[6-(trifluoromethyl)-2-pyridinyl]-7H-purin-6-yl]amino]-2-pyridinyl]acetamide	1374244: Inhibition of human His-tagged TGFbetaR1 T204D mutant expressed in Sf9 insect cells after 1 hr by HTRF assay	ic50	0.0011	uM
4-[5-(6-bromo-2-pyridinyl)-1H-pyrazol-4-yl]quinoline	132673: In vitro inhibition of transforming growth factor- beta dependent luciferase growth in mouse fibroblasts (NIH 3T3)	ic50	0.0012	uM
2-(6-methyl-2-pyridinyl)-N-pyridin-4-ylpyrrolo[2,1-f][1,2,4]triazin-4-amine	1374244: Inhibition of human His-tagged TGFbetaR1 T204D mutant expressed in Sf9 insect cells after 1 hr by HTRF assay	ic50	0.0013	uM
4-(dimethylamino)-3-[[5-(6-methyl-2-pyridinyl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-imidazol-2-yl]methylamino]benzonitrile	1142592: Inhibition of human recombinant ALK5 expressed in insect Sf9 cells using casein as substrate by radioisotopic assay	ic50	0.0013	uM
N-[4-[[2-[6-(trifluoromethyl)-2-pyridinyl]pyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]-2-pyridinyl]acetamide	1374244: Inhibition of human His-tagged TGFbetaR1 T204D mutant expressed in Sf9 insect cells after 1 hr by HTRF assay	ic50	0.0014	uM
N-[2-(3-fluorophenyl)-4-pyridinyl]-7-(4-methylsulfonylphenyl)quinolin-4-amine	1784532: Inhibition of human TGFbeta receptor 1 in human HEK293 cells preincubated for 24 hrs followed by addition of TGFbeta1 and measured after 24 hrs by luciferase based assay	ic50	0.0014	uM
7-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]-N-(2-thiophen-3-yl-4-pyridinyl)quinolin-4-amine	1784532: Inhibition of human TGFbeta receptor 1 in human HEK293 cells preincubated for 24 hrs followed by addition of TGFbeta1 and measured after 24 hrs by luciferase based assay	ic50	0.0015	uM
6-[3-(2,2-difluoroethyl)-5-(4-fluorophenyl)imidazol-4-yl]imidazo[1,2-b]pyridazine-3-carbonitrile	1542036: Inhibition of His-tagged TGFBR1 kinase domain T204D mutant (unknown origin) incubated for 1 hr by HTRF analysis	ic50	0.0016	uM
N-[2-(6-methyl-2-pyridinyl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]quinolin-4-amine	1374244: Inhibition of human His-tagged TGFbetaR1 T204D mutant expressed in Sf9 insect cells after 1 hr by HTRF assay	ic50	0.0016	uM
7-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]-N-[2-(4-methylphenyl)-4-pyridinyl]quinolin-4-amine	1784532: Inhibition of human TGFbeta receptor 1 in human HEK293 cells preincubated for 24 hrs followed by addition of TGFbeta1 and measured after 24 hrs by luciferase based assay	ic50	0.0016	uM
N-(3-fluoro-4-pyridinyl)-2-pyridin-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-amine	1374244: Inhibition of human His-tagged TGFbetaR1 T204D mutant expressed in Sf9 insect cells after 1 hr by HTRF assay	ic50	0.0017	uM
N-[2-(4-fluorophenyl)-4-pyridinyl]-7-(4-methylsulfonylphenyl)quinolin-4-amine	1784532: Inhibition of human TGFbeta receptor 1 in human HEK293 cells preincubated for 24 hrs followed by addition of TGFbeta1 and measured after 24 hrs by luciferase based assay	ic50	0.0019	uM
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	1425196: 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	0.0020	uM
N-[4-[3-[5-(trideuteriomethoxy)-2-pyridinyl]-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridinyl]acetamide	1423792: Inhibition of TGFbetaR1 T204D mutant (unknown origin) kinase domain after 1 hr by HTRF assay	ic50	0.0020	uM
N-[4-[3-(6-methyl-2-pyridinyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridinyl]acetamide	1423792: Inhibition of TGFbetaR1 T204D mutant (unknown origin) kinase domain after 1 hr by HTRF assay	ic50	0.0020	uM
N-[4-[3-[6-(trifluoromethyl)-2-pyridinyl]-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridinyl]acetamide	1423792: Inhibition of TGFbetaR1 T204D mutant (unknown origin) kinase domain after 1 hr by HTRF assay	ic50	0.0020	uM
N-[4-[3-(5-chloro-2-pyridinyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridinyl]acetamide	1423792: Inhibition of TGFbetaR1 T204D mutant (unknown origin) kinase domain after 1 hr by HTRF assay	ic50	0.0020	uM
6-[4-ethyl-1-(6-methyl-2-pyridinyl)pyrazol-5-yl]-3H-quinazolin-4-one	658823: Inhibition of ALK5	ic50	0.0020	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases reaction, increases expression, affects methylation, decreases expression	4
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, decreases activity, increases secretion, decreases reaction	4
trichostatin A	increases expression	3
Cadmium	affects cotreatment, decreases expression, increases abundance, increases expression	3
Valproic Acid	decreases expression, increases expression	3
Cyclosporine	decreases expression, decreases reaction, increases expression	3
Cadmium Chloride	increases abundance, affects cotreatment, decreases reaction, increases expression	3
aristolochic acid I	increases reaction, increases response to substance, increases expression, decreases expression	2
bisphenol A	affects binding, decreases methylation	2
ochratoxin A	increases expression	2
nickel sulfate	decreases expression	2
LY-2157299	decreases activity	2
Resveratrol	decreases reaction, increases expression	2
Acetaminophen	increases expression, decreases expression	2
Nickel	increases expression	2
Tobacco Smoke Pollution	decreases activity, decreases reaction, increases secretion, increases expression	2
WJ1376-1	decreases reaction, increases phosphorylation	1
WJ1398-1	decreases reaction, increases phosphorylation	1
vericiguat	decreases reaction, increases expression	1
FR900359	increases phosphorylation	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	decreases expression	1
moringin	increases expression	1
napabucasin	decreases expression	1
nannocystin Ax	increases expression, decreases reaction	1
cinobufagin	increases expression	1
methylmercuric chloride	increases expression	1
oxybenzone	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
piperine	affects binding	1

ChEMBL screening assays

541 unique, capped per target: 516 binding, 13 functional, 12 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1002714	Binding	Inhibition of ALK5 by filter binding assay	Synthesis and evaluation of [2-(4-quinolyloxy)phenyl]methanone derivatives: novel selective inhibitors of transforming growth factor-beta kinase. — J Med Chem
CHEMBL1107780	Functional	Antagonistic activity at TGFBR1	3D-QSAR and docking studies on transforming growth factor (TGF)-beta receptor 1 antagonists. — Bioorg Med Chem Lett
CHEMBL3998849	ADMET	Inhibition of human ALK5 using casein as substrate in presence of 10 uM ATP by radiometric kinase assay	Identification of the First Selective Activin Receptor-Like Kinase 1 Inhibitor, a Reversible Version of L-783277. — J Med Chem

Cellosaurus cell lines

14 cell lines: 9 cancer cell line, 3 induced pluripotent stem cell, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A8CZ	HEK-Blue TGF-beta	Transformed cell line	Female
CVCL_B1HZ	Abcam A-549 TGFBR1 KO	Cancer cell line	Male
CVCL_B8QS	Abcam HCT 116 TGFBR1 KO	Cancer cell line	Male
CVCL_D8CB	Ubigene A-549 TGFBR1 KO	Cancer cell line	Male
CVCL_D8X0	Ubigene HCT 116 TGFBR1 KO	Cancer cell line	Male
CVCL_D9U5	Ubigene HEK293 TGFBR1 KO	Transformed cell line	Female
CVCL_E0QV	Ubigene HeLa TGFBR1 KO	Cancer cell line	Female
CVCL_F1UH	HyCyte THP-1 KO-hTGFBR1	Cancer cell line	Male
CVCL_TS21	HAP1 TGFBR1 (-) 1	Cancer cell line	Male
CVCL_TS22	HAP1 TGFBR1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01295047	PHASE4	COMPLETED	Comparison of Medical Therapies in Marfan Syndrome.
NCT04890431	PHASE4	UNKNOWN	Impact of Oxygen Therapy on Fatigue in Patients With Hypermobile-type Ehlers-Danlos Syndrome
NCT05603741	PHASE4	ACTIVE_NOT_RECRUITING	Local Anesthetic Response in Ehlers-Danlos Syndrome (EDS) and Healthy Volunteers
NCT00339053	PHASE4	UNKNOWN	Immunonutrition and Thoracoabdominal Aorta Aneurysm Repair
NCT02291718	PHASE4	COMPLETED	Thoracoabdominal Arortic CTA Study
NCT00429364	PHASE3	COMPLETED	Comparison of Two Medications Aimed at Slowing Aortic Root Enlargement in Individuals With Marfan Syndrome
NCT00485368	PHASE3	COMPLETED	Angiotensin Converting Enzyme Inhibitors in Marfan Syndrome
NCT00683124	PHASE3	UNKNOWN	Nebivolol Versus Losartan Versus Nebivolol+Losartan Against Aortic Root Dilation in Genotyped Marfan Patients
NCT00723801	PHASE3	COMPLETED	Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome
NCT00763893	PHASE3	TERMINATED	Study of the Efficacy of Losartan on Aortic Dilatation in Patients With Marfan Syndrome
NCT00782327	PHASE3	COMPLETED	Randomized, Double-blind Study for the Evaluation of the Effect of Losartan Versus Placebo on Aortic Root Dilatation in Patients With Marfan Syndrome Under Treatment With Beta-blockers
NCT01145612	PHASE3	UNKNOWN	Atenolol Versus Losartan in the Prevention of Progressive Dilation of the Aorta in Marfan Syndrome
NCT01361087	PHASE3	WITHDRAWN	Circulating Transforming Growth Factor Beta (TGF-β) in Individuals With Marfan Syndrome
NCT01715207	PHASE3	COMPLETED	Comparison of Aliskiren vs Negative Controls on Aortic Stiffness in Patients With MFS
NCT05279937	PHASE3	NOT_YET_RECRUITING	The Ultrasound-Guided Dextrose Prolotherapy in Ehlers-Danlos Syndrome Patients
NCT00593710	PHASE2	COMPLETED	Losartan Versus Atenolol for the Treatment of Marfan Syndrome
NCT00651235	PHASE2	UNKNOWN	A Randomized, Open-label, LOSARTAN Therapy on the Progression of Aortic Root Dilation in Patients With Marfan Syndrome
NCT01949233	PHASE2	UNKNOWN	The Oxford Marfan Trial
NCT00001966	PHASE2	COMPLETED	Mind-Body Therapy for Pain in Ehlers-Danlos Syndrome
NCT01033214	PHASE1	UNKNOWN	ENTRUST - TAArget® Thoracic Stent Graft Clinical Trial
NCT03998631	PHASE1	UNKNOWN	Comparison of Carbon Dioxide and Saline Flush to Saline Flush in TEVAR and TAVI Procedures to Reduce Cerebral Ischemia
NCT01322165	Not specified	COMPLETED	National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions
NCT02050113	Not specified	RECRUITING	Complex Aortic Aneurysm Repair Using Physician Modified Endografts and Custom Made Devices
NCT02213484	Not specified	COMPLETED	Micro RNAs as a Marker of Aortic Aneurysm in Hereditary Aortopathy Syndromes
NCT02504853	Not specified	RECRUITING	Natural History and Genetics of Food Allergy and Related Conditions
NCT03440697	Not specified	ACTIVE_NOT_RECRUITING	Pathogenetic Basis of Aortopathy and Aortic Valve Disease
NCT05389865	Not specified	ACTIVE_NOT_RECRUITING	Proximal Aortopathy in Scotland - Epidemiology and Surgical Outcomes
NCT05472519	Not specified	COMPLETED	Immunopathology of Loeys-Dietz Syndrome
NCT05980104	Not specified	COMPLETED	Single-Session Empowered Relief Class for Marfan Syndrome and Related Conditions
NCT06546137	Not specified	RECRUITING	National Network for Cardiovascular Genomics: Advancing Cardiovascular Healthcare for Hereditary Diseases in Brazil’s Unified Health System Through a Multicenter Registry
NCT07360704	Not specified	COMPLETED	Genotypes and Craniofacial Phenotypes in Orthodontic Patients With Marfan and Loeys-Dietz Syndromes
NCT06783803	Not specified	ACTIVE_NOT_RECRUITING	Application of Linkage Analysis in the Identification of Novel Hereditary Factors in Familial Aneurysms
NCT00001641	Not specified	COMPLETED	Study of Heritable Connective Tissue Disorders
NCT00270686	Not specified	COMPLETED	Studies of Heritable Disorders of Connective Tissue
NCT01707563	Not specified	COMPLETED	Clinical Variability in Marfan Syndrome
NCT01760668	Not specified	COMPLETED	Aortopathy in Persons With Bicuspid Aortic Valve, Turner and Marfan Syndrome
NCT02111668	Not specified	COMPLETED	Thoracic Aortic Dilatation Syndromes
NCT02148900	Not specified	UNKNOWN	Development of a Blood Test for Marfan Syndrome
NCT02815072	Not specified	UNKNOWN	Generation of Marfan Syndrome and Fontan Cardiovascular Models Using Patient-specific Induced Pluripotent Stem Cells
NCT03236571	Not specified	COMPLETED	Cardiorespiratory and Muscular Rehabilitation of Children and Young Adults With Marfan Syndrome.