TGFB2

Summary

TGFB2 (transforming growth factor beta 2, HGNC:11768) is a protein-coding gene on chromosome 1q41, encoding Transforming growth factor beta-2 proprotein (P61812). Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively.

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGF-beta family members. Disruption of the TGF-beta/SMAD pathway has been implicated in a variety of human cancers. A chromosomal translocation that includes this gene is associated with Peters’ anomaly, a congenital defect of the anterior chamber of the eye. Mutations in this gene may be associated with Loeys-Dietz syndrome. This gene encodes multiple isoforms that may undergo similar proteolytic processing.

Source: NCBI Gene 7042 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial thoracic aortic aneurysm and aortic dissection (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 116
• Clinical variants (ClinVar): 866 total — 75 pathogenic, 39 likely-pathogenic
• Phenotypes (HPO): 108
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Transcription factor: yes — 12 downstream targets (CollecTRI)
• MANE Select transcript: NM_003238

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11768
Approved symbol	TGFB2
Name	transforming growth factor beta 2
Location	1q41
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000092969
Ensembl biotype	protein_coding
OMIM	190220
Entrez	7042

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000366929, ENST00000366930, ENST00000479322, ENST00000488793

RefSeq mRNA: 2 — MANE Select: NM_003238 NM_001135599, NM_003238

CCDS: CCDS1521, CCDS44318

Canonical transcript exons

ENST00000366930 — 7 exons

Exon	Start	End
ENSE00001000141	218434082	218434214
ENSE00001443012	218441204	218444619
ENSE00003505024	218405169	218405332
ENSE00003631099	218434338	218434448
ENSE00003637785	218435970	218436147
ENSE00003688775	218437343	218437496
ENSE00003843406	218345336	218347047

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 93.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 82.4001 / max 19696.3152, expressed in 1491 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8598	64.5702	1387
8606	8.6816	1222
8610	3.1806	840
8604	1.7127	646
8612	1.0451	557
8609	0.8851	361
8608	0.5132	224
8605	0.3100	181
8601	0.2949	140
8613	0.2423	105

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	93.21	gold quality
tendon	UBERON:0000043	91.68	gold quality
cartilage tissue	UBERON:0002418	89.46	gold quality
germinal epithelium of ovary	UBERON:0001304	87.29	gold quality
tendon of biceps brachii	UBERON:0008188	85.12	gold quality
sperm	CL:0000019	85.09	silver quality
endometrium epithelium	UBERON:0004811	83.90	gold quality
minor salivary gland	UBERON:0001830	82.96	gold quality
ventricular zone	UBERON:0003053	82.65	gold quality
male germ cell	CL:0000015	82.13	silver quality
tibia	UBERON:0000979	82.09	gold quality
islet of Langerhans	UBERON:0000006	81.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.63	gold quality
smooth muscle tissue	UBERON:0001135	81.63	gold quality
right coronary artery	UBERON:0001625	81.40	gold quality
cortical plate	UBERON:0005343	81.36	gold quality
endocervix	UBERON:0000458	80.92	gold quality
hair follicle	UBERON:0002073	80.22	gold quality
cauda epididymis	UBERON:0004360	79.56	gold quality
popliteal artery	UBERON:0002250	78.35	gold quality
tibial artery	UBERON:0007610	78.31	gold quality
left coronary artery	UBERON:0001626	78.25	gold quality
ascending aorta	UBERON:0001496	78.09	gold quality
aorta	UBERON:0000947	78.08	gold quality
right lung	UBERON:0002167	78.01	gold quality
buccal mucosa cell	CL:0002336	77.94	silver quality
thoracic aorta	UBERON:0001515	77.93	gold quality
mouth mucosa	UBERON:0003729	77.83	gold quality
ectocervix	UBERON:0012249	77.80	gold quality
saliva-secreting gland	UBERON:0001044	77.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.03

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

12 targets.

Target	Regulation
ARHGEF2	Activation
ARHGEF5	Activation
FN1	Activation
KRT1	Repression
MMP2	Activation
NET1	Repression
ROCK1	Activation
SERPINE1	Activation
SIRT1	Repression
SMAD4	Activation
SNAI1	Activation
TAGLN	Activation

Upstream regulators (CollecTRI, top): AHR, ATF1, ATF2, ATF7, BCL11B, CREB1, CTNNB1, DNMT3A, E2F1, FLCN, FOXO3, GATA2, IRF8, KDM5B, MKX, MSX2, MYC, MYCN, NKX2-1, NR3C1, PAX3, PAX6, PRRX1, RARA, RFX1, RXRA, SMAD7, TBX2, USF1, USF2, VDR, VEGFA, WT1

miRNA regulators (miRDB)

184 targeting TGFB2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AQ-5P	99.94	71.34	3426

Literature-anchored findings (GeneRIF, showing 40)

• TGFB2 induces MMP-2 expression and suppresses TIMP-2 expression. It promotes invasion of cultured glioma cells in a dose-dependent way. (PMID:11716069)
• The main source of myofibroblast-like cells and ECM production in the liver is the perisinusoidal stellate cell, which responds to injury with a pleiotypic change termed activation. Activation is orchestrated by cytokines, like tgfb2 (PMID:11795478)
• no correlation between the concentration of either isoform of TGFbeta in milk and the corresponding TGFbeta in plasma (PMID:11991670)
• a transcriptional target for Akt/protein kinase B via forkhead transcription factor. (PMID:12011061)
• TGF-beta1, TGF-beta2 and TGF-beta3 isoforms are produced by chondrosarcomas and could have a potential role as autocrine growth stimulators in these neoplasms (PMID:12021923)
• present in diabetic foot ulcer (PMID:12060054)
• Involvement of transforming growth factor-beta2 in catagen induction during the human hair cycle. (PMID:12060393)
• investigated TGF-beta 1, -beta 2, and -beta 3 latency-associated peptides (LAP)expression in sound and carious human teeth (PMID:12489185)
• Immunohistochemical double-staining of human renal sections revealed that most Tgfb2-positive cells in control glomeruli were podocytes with few Tgfb2-positive mesangial cells. (PMID:12545247)
• TGF-beta2 expression in peritoneal fibroblasts was increased by hypoxia plus TGF-beta1, but decreased by TGF-beta1 alone. (PMID:12607775)
• Glucocorticoids significantly inhibited TGF-beta1 and TGF-beta2 production and reduced expression of the up-regulated TGF-beta1 and TGF-beta2 mRNA induced by exogenous TGF-beta1, -beta2, or -beta3 (PMID:12772773)
• Data report the location and level of interleukin (IL)-8 and TGF-beta2 expression in the fimbrial compartment of fallopian tubes and IL-10 expression in the endometrium of women with pyoinflammatory adnexal diseases. (PMID:12802400)
• All three TGF-beta isoforms have fibrogenic effects on renal cells. TGF-beta2 and TGF-beta3 effects may be partially mediated by TGF-beta1. Blockade of all isoforms together may yield best therapeutic effect in reducing renal fibrosis. (PMID:12911534)
• Biological dressing effect of cultured epidermal sheets(CESs) is mediated by EGF family, TGF-beta, and VEGF. (PMID:14507446)
• In the confluent state, TGF-beta1 and TGF-beta2 stimulated the cells to progress to the S-phase of the cell cycle through platelet-derived growth factor-B (PDGF-B) chain production and protein kinase C. (PMID:14510802)
• increase of serum immunoglobulin A in newborns during 1 month of life was well correlated with levels of both transforming growth factor-beta1 and transforming growth factor-beta2 (PMID:15113633)
• Repression of promoter activity by HPV type 16 E6 and E7 proteins. (PMID:15290353)
• PSA-mediated activation of latent TGFbeta2 may be an important mechanism for autocrine TGFbeta regulation in the prostate and may potentially contribute to the formation of osteoblastic lesions in bone metastatic prostate cancer. (PMID:15389580)
• Recombinant TGF-beta 2 passes through the mouse blood-brain barrier after peripheral injection and is widely distributed throughout the brain, with highest concentrations in the hypothalamus and nerves and lowest in the cerebral hemispheres. (PMID:15695166)
• upregulation of the potent catagen inducer, transforming growth factor beta2 (TGFbeta2) by BDNF in hair follicles (PMID:15816823)
• Human TGF-beta2 but not human TGF-beta1, or -beta3 promotes cardiac myocyte differentiation from mouse ES cells. (PMID:15896309)
• TGF-beta 2 may promote endometrial tissue repair through the inhibition of the proliferation, expansion, and migration of endometrial stromal cells, and through stimulation of contraction of the collagen gel matrix by these cells. (PMID:16210002)
• TGF-beta-dependent nuclear accumulation of Smad2 is caused exclusively by selective nuclear trapping of phosphorylated, complexed Smad2 (PMID:16260601)
• The expression of TGF-beta2 mRNA was higher in cortex cataract than in nuclear cataract. (PMID:16463680)
• In conclusion, increased TGF-beta2 transcription in response to serum stimulation in KFs appears to be mediated by the p38 MAPK pathway. (PMID:16467496)
• TGF-beta2 is secreted in response to injury, significantly alters the bulk optical properties of the extracellular matrix, and its tight regulation may be required for normal collagen homeostasis. (PMID:16891397)
• The mRNA expressions of TGFbeta1 in hMSCs increased with the length of cell culture. (PMID:16998703)
• ombined effects of TGF-beta2 and connective tissue growth factor appear to be involved in the pathogenesis of proliferative vitreoretinal diseases (PMID:17192487)
• The results presented in this paper provide evidence for the involvement of an oxidative process in the apoptosis elicited by TGF-beta(2) in HLECs. (PMID:17217916)
• BMP-2, TGF-beta2, and TGF-beta3 are involved in bone formation in heterotopic ossifications. (PMID:17401695)
• No evidence for association with susceptibility or progression of MS, but have demonstrated a trend towards association of the 5’ region of the gene with susceptibility to PD. (PMID:17431704)
• TGF-beta2 triggers the malignant phenotype of high-grade gliomas by induction of migration, and that this effect is, at least in part, mediated by versican V0/V1. (PMID:17453002)
• These results suggest that FGF-2 suppresses the hMSCs cellular senescence dependent on the length of culture through down-regulation of TGF-beta2 expression. (PMID:17532297)
• Am-80-induced cell-type non-specific growth inhibition is mediated by TGF-beta2, where the total mass of RARalpha could be an important regulatory factor in hematologic malignant cells (PMID:17611697)
• TGF-beta(2) may therefore be involved in the development of childhood atopic asthma by means of functional genetic polymorphism. (PMID:17651146)
• The highest levels of active TGF-beta2 were found in keratoconus eyes. (PMID:17679942)
• TGF-beta2 promoted human lens epithelial cell adhesion and migration in vitro. Integrin beta1 and integrin-mediated signaling are necessary for TGF-beta2-promoted adhesion and migration in human lens epithelial cells. (PMID:17960115)
• TGF-beta2 and -beta3 are differentially expressed during the menstrual cycle and regulated by progesterone in epithelial vs stromal cells. (PMID:18039789)
• The early induction of TGF-beta1 at the point of SCI suggests a role in the acute inflammatory response and formation of the glial scar, while the later induction of TGF-beta2 may indicate a role in the maintenance of the scar. (PMID:18040277)
• TGFbeta2 and TbetaRII have roles in the antiestrogenic activity of tamoxifen metabolites in breast cancer (PMID:18043895)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tgfb2	ENSDARG00000027087
mus_musculus	Tgfb2	ENSMUSG00000039239
rattus_norvegicus	Tgfb2	ENSRNOG00000002418

Paralogs (31): BMP7 (ENSG00000101144), TGFB1 (ENSG00000105329), BMP5 (ENSG00000112175), BMP8B (ENSG00000116985), TGFB3 (ENSG00000119699), INHBA (ENSG00000122641), INHA (ENSG00000123999), BMP4 (ENSG00000125378), BMP2 (ENSG00000125845), GDF5 (ENSG00000125965), GDF1 (ENSG00000130283), BMP15 (ENSG00000130385), GDF15 (ENSG00000130513), GDF11 (ENSG00000135414), MSTN (ENSG00000138379), INHBE (ENSG00000139269), LEFTY2 (ENSG00000143768), GDF7 (ENSG00000143869), BMP3 (ENSG00000152785), BMP6 (ENSG00000153162), GDF6 (ENSG00000156466), NODAL (ENSG00000156574), INHBB (ENSG00000163083), BMP10 (ENSG00000163217), GDF9 (ENSG00000164404), INHBC (ENSG00000175189), BMP8A (ENSG00000183682), GDF3 (ENSG00000184344), LEFTY1 (ENSG00000243709), GDF2 (ENSG00000263761), GDF10 (ENSG00000266524)

Protein

Protein identifiers

Transforming growth factor beta-2 proprotein — P61812 (reviewed: P61812)

Alternative names: Cetermin, Glioblastoma-derived T-cell suppressor factor

All UniProt accessions (1): P61812

UniProt curated annotations — full annotation on UniProt →

Function. Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively. Required to maintain the Transforming growth factor beta-2 (TGF-beta-2) chain in a latent state during storage in extracellular matrix. Associates non-covalently with TGF-beta-2 and regulates its activation via interaction with ‘milieu molecules’, such as LTBP1 and LRRC32/GARP, that control activation of TGF-beta-2. Multifunctional protein that regulates various processes such as angiogenesis and heart development. Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains remain non-covalently linked rendering TGF-beta-2 inactive during storage in extracellular matrix. At the same time, LAP chain interacts with ‘milieu molecules’, such as LTBP1 and LRRC32/GARP, that control activation of TGF-beta-2 and maintain it in a latent state during storage in extracellular milieus. Once activated following release of LAP, TGF-beta-2 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal.

Subunit / interactions. Interacts with the serine proteases, HTRA1 and HTRA3. Interacts with ASPN. Interacts with MFAP5. Interacts with Transforming growth factor beta-2 (TGF-beta-2) chain; interaction is non-covalent and maintains (TGF-beta-2) in a latent state. Interacts with LRRC32/GARP; leading to regulate activation of TGF-beta-2. Interacts with NREP; the interaction results in a decrease in TGFB2 autoinduction. Homodimer; disulfide-linked. Interacts with TGF-beta receptors (TGFBR1 and TGFBR2), leading to signal transduction.

Subcellular location. Secreted. Extracellular space. Extracellular matrix Secreted.

Post-translational modifications. The precursor proprotein is cleaved in the Golgi apparatus to form Transforming growth factor beta-2 (TGF-beta-2) and Latency-associated peptide (LAP) chains, which remain non-covalently linked, rendering TGF-beta-2 inactive.

Disease relevance. A chromosomal aberration involving TGFB2 is found in a family with Peters anomaly. Translocation t(1;7)(q41;p21) with HDAC9. Loeys-Dietz syndrome 4 (LDS4) [MIM:614816] An aortic aneurysm syndrome with widespread systemic involvement. LDS4 is characterized by arterial tortuosity, aortic dissection, intracranial aneurysm and subarachnoid hemorrhage, hypertelorism, bifid uvula, pectus deformity, bicuspid aortic valve, arachnodactyly, scoliosis, foot deformities, dural ectasia, joint hyperflexibility, and thin skin with easy bruising and striae. The disease is caused by variants affecting the gene represented in this entry. Camurati-Engelmann disease 2 (CAEND2) [MIM:606631] A form of Camurati-Engelmann disease, an autosomal dominant disorder characterized by hyperostosis and sclerosis of the diaphyses of long bones. Sclerotic changes at the skull base may also be present. The disease typically presents in childhood with pain, muscular weakness, and waddling gait. Systemic manifestations such as anemia, leukopenia, and hepatosplenomegaly may also occur. In addition to diaphyseal dysplasia, CAEND2 affected individuals have features of osteopathia striata with cranial sclerosis. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TGF-beta family.

Isoforms (2)

UniProt ID	Names	Canonical?
P61812-1	A	yes
P61812-2	B

RefSeq proteins (2): NP_001129071, NP_003229* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001111	TGF-b_propeptide	Domain
IPR001839	TGF-b_C	Domain
IPR003940	TGFb2	Family
IPR015615	TGF-beta-like	Family
IPR016319	TGF-beta	Family
IPR017948	TGFb_CS	Conserved_site
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF00019, PF00688

UniProt features (58 total): strand 19, sequence variant 12, helix 10, disulfide bond 5, chain 3, glycosylation site 3, sequence conflict 2, turn 2, signal peptide 1, splice variant 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
2TGI	X-RAY DIFFRACTION	1.8
5TX4	X-RAY DIFFRACTION	1.88
6XM2	X-RAY DIFFRACTION	1.91
8DC0	X-RAY DIFFRACTION	1.93
1TFG	X-RAY DIFFRACTION	1.95
6I9J	X-RAY DIFFRACTION	2
8FXV	X-RAY DIFFRACTION	2.2
4KXZ	X-RAY DIFFRACTION	2.83
5TY4	ELECTRON CRYSTALLOGRAPHY	2.9
7RCO	X-RAY DIFFRACTION	2.9
8FXS	X-RAY DIFFRACTION	3.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61812-F1	80.41	0.39

Antibody-complex structures (SAbDab): 5 — 4KXZ, 6XM2, 7RCO, 8FXS, 8FXV

Functional residue map

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

Disulfide bonds (5): 350–413, 379, 309–318, 317–380, 346–411

Glycosylation sites (3): 72, 140, 241

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-2129379	Molecules associated with elastic fibres
R-HSA-2173789	TGF-beta receptor signaling activates SMADs
R-HSA-3000178	ECM proteoglycans
R-HSA-9839389	TGFBR3 regulates TGF-beta signaling
R-HSA-109582	Hemostasis
R-HSA-1474244	Extracellular matrix organization
R-HSA-1566948	Elastic fibre formation
R-HSA-162582	Signal Transduction
R-HSA-170834	Signaling by TGF-beta Receptor Complex
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+
R-HSA-9006936	Signaling by TGFB family members
R-HSA-9839373	Signaling by TGFBR3

MSigDB gene sets: 968 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_BODY_MORPHOGENESIS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_EPIDERMIS_MORPHOGENESIS, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX

GO Biological Process (119): cell morphogenesis (GO:0000902), skeletal system development (GO:0001501), cartilage condensation (GO:0001502), eye development (GO:0001654), response to hypoxia (GO:0001666), kidney development (GO:0001822), epithelial to mesenchymal transition (GO:0001837), neural tube closure (GO:0001843), hair follicle development (GO:0001942), blood vessel remodeling (GO:0001974), heart morphogenesis (GO:0003007), outflow tract septum morphogenesis (GO:0003148), membranous septum morphogenesis (GO:0003149), heart valve morphogenesis (GO:0003179), atrioventricular valve morphogenesis (GO:0003181), pulmonary valve morphogenesis (GO:0003184), endocardial cushion morphogenesis (GO:0003203), cardiac right ventricle morphogenesis (GO:0003215), ventricular trabecula myocardium morphogenesis (GO:0003222), endocardial cushion fusion (GO:0003274), atrial septum primum morphogenesis (GO:0003289), neural retina development (GO:0003407), activation-induced cell death of T cells (GO:0006924), transforming growth factor beta receptor signaling pathway (GO:0007179), axon guidance (GO:0007411), salivary gland morphogenesis (GO:0007435), heart development (GO:0007507), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), glial cell migration (GO:0008347), male gonad development (GO:0008584), response to wounding (GO:0009611), embryo development ending in birth or egg hatching (GO:0009792), cardioblast differentiation (GO:0010002), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), positive regulation of epithelial cell migration (GO:0010634), positive regulation of epithelial to mesenchymal transition (GO:0010718), negative regulation of macrophage cytokine production (GO:0010936), cell migration (GO:0016477)

GO Molecular Function (9): amyloid-beta binding (GO:0001540), signaling receptor binding (GO:0005102), type II transforming growth factor beta receptor binding (GO:0005114), cytokine activity (GO:0005125), transforming growth factor beta receptor binding (GO:0005160), growth factor activity (GO:0008083), type III transforming growth factor beta receptor binding (GO:0034714), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endosome (GO:0005768), axon (GO:0030424), extracellular matrix (GO:0031012), platelet alpha granule lumen (GO:0031093), neuronal cell body (GO:0043025)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Extracellular matrix organization	2
Signaling by TGFB family members	2
Response to elevated platelet cytosolic Ca2+	1
Elastic fibre formation	1
Signaling by TGF-beta Receptor Complex	1
Signaling by TGFBR3	1
Hemostasis	1
Platelet activation, signaling and aggregation	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure morphogenesis	3
heart valve morphogenesis	2
transforming growth factor beta receptor binding	2
receptor ligand activity	2
system development	1
skeletal system morphogenesis	1
cartilage development	1
cell aggregation	1
sensory organ development	1
visual system development	1
response to stress	1
response to decreased oxygen levels	1
animal organ development	1
renal system development	1
mesenchymal cell differentiation	1
primary neural tube formation	1
tube closure	1
hair cycle process	1
anatomical structure development	1
skin epidermis development	1
tissue remodeling	1
heart development	1
animal organ morphogenesis	1
outflow tract morphogenesis	1
cardiac septum morphogenesis	1
ventricular septum morphogenesis	1
heart valve development	1
atrioventricular valve development	1
pulmonary valve development	1
heart morphogenesis	1
endocardial cushion development	1
mesenchyme morphogenesis	1
cardiac ventricle morphogenesis	1
ventricular cardiac muscle tissue morphogenesis	1
heart trabecula morphogenesis	1
endocardial cushion morphogenesis	1
cell adhesion involved in heart morphogenesis	1
cell-cell adhesion	1
peptide binding	1
protein binding	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

23 interactions, top by confidence:

A	B	Type	Score
TGFB2	APP	psi-mi:“MI:2364”(proximity)	0.700
TGFB2	APP	psi-mi:“MI:0915”(physical association)	0.700
APP	TGFB1	psi-mi:“MI:0914”(association)	0.600
UNG	TGFB2	psi-mi:“MI:0915”(physical association)	0.560
TGFB1	LAMC1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
TGFB2	LTBP4	psi-mi:“MI:0915”(physical association)	0.400
P		psi-mi:“MI:0914”(association)	0.350
	TOR1B	psi-mi:“MI:0914”(association)	0.350
LY6H	NXPH4	psi-mi:“MI:0914”(association)	0.350
ADIPOQ	AGRN	psi-mi:“MI:0914”(association)	0.350
C1orf54	QSOX1	psi-mi:“MI:0914”(association)	0.350
FBXO6	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LRRC32	ORC4	psi-mi:“MI:0914”(association)	0.350
PATE1	AGRN	psi-mi:“MI:0914”(association)	0.350
TGFB2	BMP2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (20): APP (Co-localization), BMP2 (Co-localization), TGFB2 (Affinity Capture-MS), TGFB2 (Reconstituted Complex), TGFB2 (Affinity Capture-MS), TGFB2 (Affinity Capture-MS), TGFB2 (Affinity Capture-MS), TGFB2 (Affinity Capture-MS), TGFB2 (Proximity Label-MS), TGFB2 (Affinity Capture-Western), TGFB2 (Reconstituted Complex), DCN (Reconstituted Complex), TGFB2 (Affinity Capture-MS), TGFB2 (Affinity Capture-MS), TGFB2 (Reconstituted Complex)

ESM2 similar proteins: A0A1D5PUP4, A5YT95, O35757, O62650, O75882, O95980, P07225, P09858, P10669, P17247, P19883, P21214, P21674, P26012, P26013, P27090, P30371, P31514, P31515, P47931, P49767, P50291, P61811, P61812, P97299, P97953, Q07257, Q0VBD0, Q17QD6, Q38L25, Q5RA73, Q6NW40, Q6V9H4, Q6ZQ11, Q863H1, Q86X52, Q8BFR2, Q8CI19, Q8JG54, Q8N475

Diamond homologs: A8E7N9, G5EEL5, O08717, O13048, O19006, O46564, O46576, O61643, O88959, O95393, P04088, P07713, P08476, P09529, P09534, P09858, P10600, P12643, P12645, P15203, P16176, P17125, P17491, P18075, P18331, P20722, P20863, P21214, P21274, P21275, P22003, P22004, P22444, P23359, P25703, P27090, P27091, P27093, P30884, P30885

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
TGFB2	up-regulates	TGFBR2	binding
TGFB2	up-regulates	TGFB2	binding
TGFB2	up-regulates	TGFBR1	binding
TGFB2	“down-regulates quantity by repression”	KRT1	“transcriptional regulation”
“Activated PSC”	“up-regulates quantity”	TGFB2
TGFB2	up-regulates	“Activated PSC”
TGFB2	up-regulates	TGFBR3	binding
TGFB2	up-regulates	Angiogenesis

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 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
Extracellular matrix organization	6	27.0×	7e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	75
Likely pathogenic	39
Uncertain significance	407
Likely benign	237
Benign	37

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068936	NM_003238.6(TGFB2):c.986dup (p.Asp329fs)	Pathogenic
1075270	NM_003238.6(TGFB2):c.194dup (p.Glu66fs)	Pathogenic
1076183	NM_003238.6(TGFB2):c.404C>G (p.Ser135Ter)	Pathogenic
1199382	Single allele	Pathogenic
1205778	NM_003238.6(TGFB2):c.821del (p.Asn274fs)	Pathogenic
1299635	NM_003238.6(TGFB2):c.912_930del (p.Asp305fs)	Pathogenic
1300138	NM_003238.6(TGFB2):c.1012C>A (p.Pro338Thr)	Pathogenic
1351917	NM_003238.6(TGFB2):c.456dup (p.Arg153fs)	Pathogenic
1393330	NM_003238.6(TGFB2):c.329_330dup (p.Phe111fs)	Pathogenic
1451388	NM_003238.6(TGFB2):c.145A>T (p.Lys49Ter)	Pathogenic
1452939	NM_003238.6(TGFB2):c.196del (p.Glu66fs)	Pathogenic
1452940	NM_003238.6(TGFB2):c.171T>A (p.Tyr57Ter)	Pathogenic
1455704	NC_000001.10:g.(?218520044)(218607810_?)del	Pathogenic
1458168	NC_000001.10:g.(?218520044)(218614704_?)del	Pathogenic
1458546	NM_003238.6(TGFB2):c.868dup (p.Arg290fs)	Pathogenic
1702284	NM_003238.6(TGFB2):c.1041del (p.Gly348fs)	Pathogenic
1737850	NM_003238.6(TGFB2):c.41_42insTATCT (p.Val15fs)	Pathogenic
1797425	NM_003238.6(TGFB2):c.28del (p.Phe9_Leu10insTer)	Pathogenic
1804997	NM_003238.6(TGFB2):c.127C>T (p.Gln43Ter)	Pathogenic
2002460	NM_003238.6(TGFB2):c.655G>T (p.Gly219Ter)	Pathogenic
2031447	NM_003238.6(TGFB2):c.765del (p.Thr256fs)	Pathogenic
213841	NM_003238.6(TGFB2):c.583G>T (p.Glu195Ter)	Pathogenic
213852	NM_003238.6(TGFB2):c.356del (p.Pro119fs)	Pathogenic
2151918	NM_003238.6(TGFB2):c.589G>T (p.Glu197Ter)	Pathogenic
224873	NM_003238.6(TGFB2):c.1022_1026del (p.Tyr341fs)	Pathogenic
224874	NM_003238.6(TGFB2):c.297C>A (p.Tyr99Ter)	Pathogenic
2452021	NM_003238.6(TGFB2):c.375_378del (p.Tyr126fs)	Pathogenic
2576784	NM_003238.6(TGFB2):c.643+1G>A	Pathogenic
2730244	NM_003238.6(TGFB2):c.678T>A (p.Cys226Ter)	Pathogenic
2752143	NM_003238.6(TGFB2):c.89del (p.Asp30fs)	Pathogenic

SpliceAI

1767 predictions. Top by Δscore:

Variant	Effect	Δscore
1:218347005:G:GT	donor_gain	1.0000
1:218347043:CGAAA:C	donor_gain	1.0000
1:218347044:GAAA:G	donor_gain	1.0000
1:218347044:GAAAG:G	donor_gain	1.0000
1:218347045:AAA:A	donor_gain	1.0000
1:218347046:AA:A	donor_gain	1.0000
1:218347047:AGTA:A	donor_loss	1.0000
1:218347048:G:C	donor_loss	1.0000
1:218347048:G:GG	donor_gain	1.0000
1:218405164:TACA:T	acceptor_loss	1.0000
1:218405165:ACAG:A	acceptor_loss	1.0000
1:218405168:GAT:G	acceptor_gain	1.0000
1:218405330:CAGGT:C	donor_loss	1.0000
1:218405331:AGGT:A	donor_loss	1.0000
1:218405334:T:A	donor_loss	1.0000
1:218434077:TCCAG:T	acceptor_loss	1.0000
1:218434080:A:AG	acceptor_gain	1.0000
1:218434081:G:GC	acceptor_gain	1.0000
1:218434081:GA:G	acceptor_gain	1.0000
1:218434081:GAT:G	acceptor_gain	1.0000
1:218434081:GATT:G	acceptor_gain	1.0000
1:218434081:GATTC:G	acceptor_gain	1.0000
1:218437492:GCAGG:G	donor_gain	1.0000
1:218437495:GG:G	donor_gain	1.0000
1:218437496:GG:G	donor_gain	1.0000
1:218437497:G:GG	donor_gain	1.0000
1:218347051:A:AG	donor_gain	0.9900
1:218347052:G:GG	donor_gain	0.9900
1:218402945:C:G	donor_gain	0.9900
1:218405167:A:AG	acceptor_gain	0.9900

AlphaMissense

2744 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:218346835:T:C	L45P	1.000
1:218346844:T:C	L48P	1.000
1:218405325:T:C	L168P	1.000
1:218434119:G:C	R183P	1.000
1:218434199:T:A	W210R	1.000
1:218434199:T:C	W210R	1.000
1:218434201:G:C	W210C	1.000
1:218434201:G:T	W210C	1.000
1:218434370:T:C	C226R	1.000
1:218436057:T:C	L281P	1.000
1:218436142:C:G	C309W	1.000
1:218437359:T:A	C317S	1.000
1:218437359:T:C	C317R	1.000
1:218437360:G:A	C317Y	1.000
1:218437360:G:C	C317S	1.000
1:218437361:C:G	C317W	1.000
1:218437386:T:C	F326L	1.000
1:218437387:T:C	F326S	1.000
1:218437387:T:G	F326C	1.000
1:218437388:C:A	F326L	1.000
1:218437388:C:G	F326L	1.000
1:218437404:T:A	W332R	1.000
1:218437404:T:C	W332R	1.000
1:218437406:G:C	W332C	1.000
1:218437406:G:T	W332C	1.000
1:218437410:T:A	W334R	1.000
1:218437410:T:C	W334R	1.000
1:218437412:G:C	W334C	1.000
1:218437412:G:T	W334C	1.000
1:218437446:T:A	C346S	1.000

dbSNP variants (sampled 300 via entrez): RS1000003571 (1:218382048 C>T), RS1000070019 (1:218383431 A>G), RS1000104935 (1:218421410 T>C), RS1000105259 (1:218422123 A>G), RS1000105509 (1:218381675 A>C,G), RS1000180010 (1:218398284 T>C), RS1000191803 (1:218444924 G>A,C), RS1000232465 (1:218397825 C>G), RS1000286648 (1:218353823 G>A), RS1000298719 (1:218404163 A>G), RS1000322551 (1:218399840 C>A), RS1000362986 (1:218347750 C>T), RS1000364489 (1:218415414 G>A,C,T), RS1000414365 (1:218432954 G>A), RS1000443019 (1:218427648 T>C,G)

Disease associations

OMIM: gene MIM:190220 | disease phenotypes: MIM:614816, MIM:607086, MIM:108800, MIM:130000, MIM:609192, MIM:142900, MIM:142623, MIM:606631, MIM:154700

GenCC curated gene-disease

Disease	Classification	Inheritance
Loeys-Dietz syndrome 4	Definitive	Autosomal dominant
familial thoracic aortic aneurysm and aortic dissection	Definitive	Unknown

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
familial thoracic aortic aneurysm and aortic dissection	Definitive	AD

Mondo (14): Loeys-Dietz syndrome 4 (MONDO:0013897), familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625), atrial septal defect 1 (MONDO:0007172), Ehlers-Danlos syndrome (MONDO:0020066), Loeys-Dietz syndrome (MONDO:0018954), Holt-Oram syndrome (MONDO:0007732), connective tissue disorder (MONDO:0003900), Hirschsprung disease, susceptibility to, 1 (MONDO:0007723), proteinuria (MONDO:0003634), aortic aneurysm (MONDO:0005160), lung adenocarcinoma (MONDO:0005061), Camurati-Engelmann disease type 2 (MONDO:0011690), allergic disease (MONDO:0005271), Marfan syndrome (MONDO:0007947)

Orphanet (9): Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387), Interatrial communication (Orphanet:1478), Ehlers-Danlos syndrome (Orphanet:98249), Loeys-Dietz syndrome (Orphanet:60030), Holt-Oram syndrome (Orphanet:392), Hirschsprung disease (Orphanet:388), Marfan syndrome type 1 (Orphanet:284963), Marfan syndrome (Orphanet:558), NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268)

HPO phenotypes

108 total (30 of 108 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000098	Tall stature
HP:0000135	Hypogonadism
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000202	Orofacial cleft
HP:0000218	High palate
HP:0000268	Dolichocephaly
HP:0000272	Malar flattening
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000473	Torticollis
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000525	Abnormality iris morphology
HP:0000545	Myopia
HP:0000592	Blue sclerae
HP:0000766	Abnormal sternum morphology
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000822	Hypertension
HP:0000823	Delayed puberty
HP:0000938	Osteopenia
HP:0000963	Thin skin
HP:0000964	Eczematoid dermatitis
HP:0000965	Cutis marmorata
HP:0000973	Cutis laxa

GWAS associations

116 associations (top):

Study	Trait	p-value
GCST000817_152	Height	2.000000e-12
GCST001248_5	Pulmonary function	1.000000e-08
GCST002350_6	Chronic obstructive pulmonary disease (severe)	8.000000e-09
GCST002481_4	Acne (severe)	4.000000e-08
GCST002525_17	Local histogram emphysema pattern	7.000000e-09
GCST002525_22	Local histogram emphysema pattern	3.000000e-09
GCST002525_3	Local histogram emphysema pattern	3.000000e-08
GCST002525_8	Local histogram emphysema pattern	8.000000e-09
GCST002647_1	Height	2.000000e-26
GCST002647_16	Height	2.000000e-13
GCST002702_30	Height	6.000000e-13
GCST002945_28	Emphysema imaging phenotypes	5.000000e-07
GCST003262_1040	Post bronchodilator FEV1	8.000000e-07
GCST003262_1041	Post bronchodilator FEV1	8.000000e-07
GCST003262_1046	Post bronchodilator FEV1	1.000000e-06
GCST003262_1160	Post bronchodilator FEV1	1.000000e-06
GCST003262_1173	Post bronchodilator FEV1	8.000000e-07
GCST003262_1174	Post bronchodilator FEV1	9.000000e-07
GCST003262_1175	Post bronchodilator FEV1	9.000000e-07
GCST003262_145	Post bronchodilator FEV1	1.000000e-06
GCST003262_189	Post bronchodilator FEV1	6.000000e-07
GCST003262_425	Post bronchodilator FEV1	1.000000e-08
GCST003262_61	Post bronchodilator FEV1	3.000000e-07
GCST003262_62	Post bronchodilator FEV1	4.000000e-07
GCST003262_679	Post bronchodilator FEV1	5.000000e-07
GCST003262_686	Post bronchodilator FEV1	3.000000e-06
GCST003262_793	Post bronchodilator FEV1	2.000000e-07
GCST003262_926	Post bronchodilator FEV1	1.000000e-06
GCST003264_1114	Post bronchodilator FEV1/FVC ratio	2.000000e-07
GCST003264_1117	Post bronchodilator FEV1/FVC ratio	5.000000e-07

EFO canonical traits (23, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio
EFO:0005850	emphysema pattern measurement
EFO:0007626	emphysema imaging measurement
EFO:0004314	forced expiratory volume
EFO:0007873	cartilage thickness measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0004695	intraocular pressure measurement
EFO:0005213	central corneal thickness
EFO:0009180	rosacea severity measurement
EFO:0007702	hip bone mineral density
EFO:0006336	diastolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure
EFO:0004341	body fat distribution
EFO:0004312	vital capacity
EFO:0009718	peak expiratory flow
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0006939	cup-to-disc ratio measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D001014	Aortic Aneurysm	C14.907.055.239; C14.907.109.139
D003240	Connective Tissue Diseases	C17.300
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
D006967	Hypersensitivity	C20.543
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
D011507	Proteinuria	C12.050.351.968.934.734; C12.200.777.934.734; C12.950.934.734; C23.888.942.750
C537978	Camurati Engelmann disease, type 2 (supp.)
C535326	Holt-Oram syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3217393 (SINGLE PROTEIN), CHEMBL3988637 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,929 (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
CHEMBL2364611	GALUNISERTIB	2	1,929

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1418553	TGFB2		0.00	0

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.47	IC50	0.34	nM	CHEMBL5288544
8.36	IC50	4.33	nM	CHEMBL3704651
7.25	IC50	56	nM	GALUNISERTIB
6.01	IC50	970	nM	CHEMBL5279930

PubChem BioAssay actives

4 with measured affinity, of 4 total; 4 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-(5-fluoro-6-methyl-2-pyridinyl)-7H-purin-6-yl]amino]-2-pyridinyl]acetamide	1960097: Inhibition of TGF-beta (unknown origin)	ic50	0.0003	uM
2-[4-ethyl-1-(6-methyl-2-pyridinyl)pyrazol-5-yl]thieno[3,2-c]pyridine	1960097: Inhibition of TGF-beta (unknown origin)	ic50	0.0043	uM
4-[2-(6-methyl-2-pyridinyl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide	1960097: Inhibition of TGF-beta (unknown origin)	ic50	0.0560	uM
5-[3-(hydroxymethyl)phenyl]-3-(6-piperazin-1-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one	1960097: Inhibition of TGF-beta (unknown origin)	ic50	0.9700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects binding, affects cotreatment, increases expression, decreases expression, decreases reaction (+1 more)	14
sodium arsenite	affects cotreatment, decreases expression, increases expression	9
Benzo(a)pyrene	increases expression, decreases expression, decreases methylation	6
Tretinoin	increases expression, increases secretion, decreases reaction	6
bisphenol A	affects expression, decreases expression, decreases methylation	5
Valproic Acid	affects cotreatment, increases expression, decreases expression, decreases methylation	5
Resveratrol	affects cotreatment, decreases expression, decreases reaction, increases expression, affects binding (+1 more)	4
Calcitriol	increases expression, affects cotreatment	3
Tetrachlorodibenzodioxin	increases expression, affects cotreatment, decreases expression, decreases chemical synthesis	3
Cadmium Chloride	decreases expression, increases abundance, increases expression, affects cotreatment	3
Raloxifene Hydrochloride	affects expression, affects cotreatment, increases expression	3
trichostatin A	decreases expression, increases expression	2
arsenite	decreases reaction, decreases expression	2
dimethylarsinous acid	increases expression	2
(+)-JQ1 compound	decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Cisplatin	increases expression, affects cotreatment, decreases expression, decreases response to substance	2
Ethinyl Estradiol	affects expression, decreases expression	2
Hydrogen Peroxide	affects cotreatment, affects reaction, affects response to substance, increases expression	2
Nickel	decreases expression	2
Polychlorinated Biphenyls	affects expression, decreases expression	2
Progesterone	affects cotreatment, decreases expression	2
Tamoxifen	affects expression, affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression	2
Triclosan	decreases expression, affects expression	2
Cyclosporine	affects expression, decreases expression	2
Aflatoxin B1	increases expression	2
Genistein	decreases expression	2
aristolochic acid I	decreases expression	1
Glupearl 19S	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3225605	Binding	Binding affinity to human TGFbeta2 (amino acid residues A1 to S112) at 0.125 to 2 uM by surface plasmon resonance assay	Binding region and interaction properties of sulfoquinovosylacylglycerol (SQAG) with human vascular endothelial growth factor 165 revealed by biosensor-based assays — Medchemcomm

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1ZB	Abcam A-549 TGFB2 KO	Cancer cell line	Male
CVCL_D2DC	Abcam HCT 116 TGFB2 KO	Cancer cell line	Male
CVCL_D8CA	Ubigene A-549 TGFB2 KO	Cancer cell line	Male
CVCL_DC99	CHO 1beta9, 12.5, clone 36	Transformed cell line	Female
CVCL_DD00	CHO beta2(414)cl.32	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT02343562	PHASE4	UNKNOWN	Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis
NCT07186647	PHASE4	COMPLETED	Laparoscopic-Assisted Transanal Pull-Through for Hirschsprung Disease in Pediatric:Short and Intermediate Outcomes of Two Different Techniques
NCT05279937	PHASE3	NOT_YET_RECRUITING	The Ultrasound-Guided Dextrose Prolotherapy in Ehlers-Danlos Syndrome Patients
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT04904081	PHASE3	UNKNOWN	Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery
NCT00001966	PHASE2	COMPLETED	Mind-Body Therapy for Pain in Ehlers-Danlos Syndrome
NCT00004357	PHASE2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	PHASE2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	PHASE2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
NCT02682511	PHASE2	ACTIVE_NOT_RECRUITING	Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04993885	PHASE2	RECRUITING	Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT05516758	PHASE2	TERMINATED	A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis
NCT05998759	PHASE2	RECRUITING	Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
NCT06104228	PHASE2	RECRUITING	129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)
NCT00630838	PHASE2	COMPLETED	Probiotic Prophylaxis of Hirschprung’s Disease Associated Enterocolitis (HAEC)
NCT01093911	PHASE1	COMPLETED	Safety Study of CDP7657 in Healthy Volunteers and Patients With Systemic Lupus Erythematosus (SLE)
NCT01764594	PHASE1	COMPLETED	Safety Study of CDP7657 in Patients With Systemic Lupus Erythematosus
NCT02392130	PHASE1	COMPLETED	A Clinical Trial to Assess the Potential of LEO 130852A Gel to Reduce Steroid Induced Skin Atrophy on Healthy Skin
NCT03337165	PHASE1	COMPLETED	Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
NCT03929120	PHASE1	COMPLETED	Allogeneic Bone Marrow Mesenchymal Stem Cells for Patients With Interstitial Lung Disease (ILD) & Connective Tissue Disorders (CTD)
NCT03440697	Not specified	ACTIVE_NOT_RECRUITING	Pathogenetic Basis of Aortopathy and Aortic Valve Disease
NCT06783803	Not specified	ACTIVE_NOT_RECRUITING	Application of Linkage Analysis in the Identification of Novel Hereditary Factors in Familial Aneurysms