ENG

Summary

ENG (endoglin, HGNC:3349) is a protein-coding gene on chromosome 9q34.11, encoding Endoglin (P17813). Vascular endothelium glycoprotein that plays an important role in the regulation of angiogenesis. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a homodimeric transmembrane protein which is a major glycoprotein of the vascular endothelium. This protein is a component of the transforming growth factor beta receptor complex and it binds to the beta1 and beta3 peptides with high affinity. Mutations in this gene cause hereditary hemorrhagic telangiectasia, also known as Osler-Rendu-Weber syndrome 1, an autosomal dominant multisystemic vascular dysplasia. This gene may also be involved in preeclampsia and several types of cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2022 — RefSeq curated summary.

At a glance

• Gene–disease (curated): telangiectasia, hereditary hemorrhagic, type 1 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 1,995 total — 492 pathogenic, 102 likely-pathogenic
• Phenotypes (HPO): 89
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001114753

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3349
Approved symbol	ENG
Name	endoglin
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	END, HHT1, CD105
Ensembl gene	ENSG00000106991
Ensembl biotype	protein_coding
OMIM	131195
Entrez	2022

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 35 protein_coding, 5 nonsense_mediated_decay, 1 retained_intron

ENST00000344849, ENST00000373203, ENST00000462196, ENST00000480266, ENST00000486329, ENST00000713956, ENST00000713957, ENST00000713995, ENST00000713996, ENST00000713997, ENST00000714046, ENST00000714047, ENST00000714076, ENST00000714077, ENST00000714078, ENST00000714079, ENST00000714080, ENST00000714081, ENST00000714082, ENST00000714083, ENST00000714084, ENST00000714102, ENST00000714103, ENST00000714126, ENST00000714127, ENST00000886302, ENST00000886303, ENST00000886304, ENST00000886305, ENST00000886306, ENST00000886307, ENST00000886308, ENST00000886309, ENST00000886310, ENST00000942917, ENST00000942918, ENST00000942919, ENST00000942920, ENST00000942921, ENST00000942922, ENST00000942923

RefSeq mRNA: 4 — MANE Select: NM_001114753 NM_000118, NM_001114753, NM_001278138, NM_001406715

CCDS: CCDS48029, CCDS6880, CCDS75906

Canonical transcript exons

ENST00000373203 — 15 exons

Exon	Start	End
ENSE00000729960	127818716	127818832
ENSE00000729963	127819622	127819660
ENSE00001181098	127815943	127816053
ENSE00001181101	127854289	127854658
ENSE00003297799	127829687	127829827
ENSE00003346729	127843094	127843245
ENSE00003438349	127825695	127825860
ENSE00003486427	127826510	127826672
ENSE00003605233	127819900	127820037
ENSE00003730037	127824304	127824446
ENSE00003736678	127818120	127818377
ENSE00003738385	127824800	127824974
ENSE00003742131	127817149	127817203
ENSE00004022109	127825231	127825357
ENSE00004022732	127815016	127815806

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 99.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 68.3270 / max 1114.6175, expressed in 1387 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102598	29.4691	1210
102600	18.3331	1312
102599	14.4962	1211
102595	2.6488	729
102597	1.9820	487
102601	0.6847	365
102596	0.5039	264
102594	0.2092	75

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	99.49	gold quality
right atrium auricular region	UBERON:0006631	99.35	gold quality
cardiac atrium	UBERON:0002081	99.23	gold quality
apex of heart	UBERON:0002098	99.22	gold quality
right lobe of thyroid gland	UBERON:0001119	99.10	gold quality
left ovary	UBERON:0002119	99.05	gold quality
metanephros cortex	UBERON:0010533	99.02	gold quality
right ovary	UBERON:0002118	99.00	gold quality
right coronary artery	UBERON:0001625	98.97	gold quality
upper lobe of left lung	UBERON:0008952	98.92	gold quality
ascending aorta	UBERON:0001496	98.90	gold quality
thoracic aorta	UBERON:0001515	98.89	gold quality
descending thoracic aorta	UBERON:0002345	98.84	gold quality
left coronary artery	UBERON:0001626	98.75	gold quality
upper lobe of lung	UBERON:0008948	98.72	gold quality
coronary artery	UBERON:0001621	98.69	gold quality
omental fat pad	UBERON:0010414	98.69	gold quality
peritoneum	UBERON:0002358	98.64	gold quality
left lobe of thyroid gland	UBERON:0001120	98.61	gold quality
left uterine tube	UBERON:0001303	98.50	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.42	gold quality
spleen	UBERON:0002106	98.34	gold quality
heart left ventricle	UBERON:0002084	98.20	gold quality
endocervix	UBERON:0000458	98.09	gold quality
cardiac ventricle	UBERON:0002082	98.09	gold quality
body of uterus	UBERON:0009853	97.98	gold quality
right uterine tube	UBERON:0001302	97.97	gold quality
thyroid gland	UBERON:0002046	97.85	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.85	gold quality
heart	UBERON:0000948	97.77	gold quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	2466.23
E-GEOD-135922	yes	2231.89
E-MTAB-8142	yes	1832.49
E-MTAB-6678	yes	1584.50
E-HCAD-11	yes	1195.16
E-HCAD-9	yes	903.23
E-MTAB-10287	yes	654.45
E-GEOD-100618	yes	213.94
E-MTAB-6701	yes	74.34
E-HCAD-10	yes	62.45
E-MTAB-10553	yes	60.74
E-HCAD-1	yes	50.39
E-MTAB-8410	yes	38.31
E-CURD-46	yes	34.54
E-CURD-119	yes	27.95

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
BMP2	Activation
CD34	Repression
SNAI1	Activation

Upstream regulators (CollecTRI, top): ACVRL1, EGR1, ELF1, ERG, GDF2, HIF1A, KLF4, KLF6, NR1H3, SP1, SSRP1, TGFB1

miRNA regulators (miRDB)

45 targeting ENG, 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-4283	100.00	66.42	2097
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-3920	97.75	69.02	1168

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• mutational analysis and genetic epidemiology of hereditary hemorrhagic telangiectasia in a local community (Akita prefecture) in northern Japan (PMID:11793473)
• CLL B cells consistently express endoglin mRNA; co-expression of angiogenic molecules and receptors suggest autocrine pathways of stimulation. (PMID:11986954)
• expression marks principally small, probably newly formed tumor vessels in the prostate and is a promising prognostic marker for prostate cancer (PMID:11987155)
• endoglin expression on dermal endothelial cells was significantly enhanced in scleroderma but levels on circulating monocytes and in the serum were within normal limits (PMID:12009077)
• Extracellular and cytoplasmic domains of endoglin interact with tgf-beta I and II receptors (PMID:12015308)
• basal endoglin transcription (highly dependent on Sp1) may switch from a constitutive to an inducible state through Sp1 interaction with HIF-1 and Smad transcription factors, induced by hypoxia and TGF-beta, respectively (PMID:12228247)
• Inducible expression of human endoglin during inflammation and wound healing in vivo. Changes in endoglin expression from the normal quiescent state through the inflammatory changes and angiogenesis during dermal wound healing. (PMID:12365720)
• identified as a regulator of cell adhesion, motility and invasion in human prostate; loss of endoglin expression appears to be associated with prostate cancer progression, at least in vitro (PMID:12447690)
• endoglin and betaglycan have a critical role in the regulation of TGFbeta signaling in chondrocytes (PMID:12568406)
• No association was found between the 6bINS polymorphism or 4 SNPs in endoglin (ENG) and intracranial aneurysm (IA) and no linkage between the ENG locus and IA, indicating ENG is not a major susceptibility gene for IA in a Japanese population (PMID:12775886)
• Tumour microvessel density quantified using a Mab to CD105 is an independent prognostic parameter for survival of patients with colorectal cancer (PMID:12778073)
• study showed that endoglin, by staining the proliferating microvessels in endometrial carcinoma, is a more specific and sensitive marker for tumor angiogenesis than is the commonly used pan-endothelial marker, CD31 antigen (PMID:12819391)
• Up-regulation of CD105 in synovial cells of rheumatoid arthritis & psoriatic lesions implies a possible role in their pathogenesis. CD105 gene expression in endothelial cells is downregulated by the TNF alpha & downregulated by TGF beta 1. (PMID:12820370)
• A questionnaire based study provides evidence that the hereditary hemorrhagic telangietasia (HHT) phenotype caused by mutations in endoglin (HHT1) is distinct from, and more severe than, HHT caused by mutations in ALK1 (HHT2). (PMID:12920067)
• cell membrane glycoprotein expressed on endothelial cells and on tumor-associated vascular endothelium; accessory component of the transforming growth factor -beta receptor complex and is involved in vascular development and remodelling (review) (PMID:14528280)
• CD105, as a receptor of TGF-beta1, can regulate the biological effect of TGF-beta1 in tumor angiogenesis. (PMID:14669355)
• It is concluded that CD105 immunoexpression in breast carcinomas is an independent prognostic indicator in node-negative patients, better in terms of overall survival than Tie-2/Tek and CD31 (PMID:14991534)
• Inverse regulation in the expression of endoglin and lumican. (PMID:14996436)
• Mutational analysis of the ENG gene in hereditary hemorrhagic telangiectasia patients. (PMID:15024723)
• Increased CD105 expression is associated with high risk for metastasis of breast carcinomas (PMID:15067342)
• Endoglin interacts with LIM domain-containing proteins, and associated adapter proteins, affecting sites of focal adhesion. (PMID:15084601)
• Endoglin-dependent inhibition of cell migration, reduction of focal adhesion-associated p130(cas)/CrkII protein levels, tyrosine phosphorylation of p130(cas), and focal adhesion-associated endoglin levels are mediated by the cytosolic domain. (PMID:15084601)
• Endoglin regulates cytoskeletal organization through binding to ZRP-1, a member of the Lim family of proteins (PMID:15148318)
• CD105-determined microvascular density correlates with the degree of fibrosis and is prognostically relevant and findings provide a rationale for the investigational use of anti-CD105-targeted drugs in chronic idiopathic myelofibrosis (CIMF). (PMID:15272276)
• VEGF mRNA expression levels seem to be directly associated with VEGF functions at the protein levelin breast cancer, whereas this seems not to be the case for CD105 (endoglin) mRNA levels. (PMID:15274325)
• Endoglin expression negatively regulates basal and TGF-beta1-induced CTGF and collagen expression and synthesis. (PMID:15319534)
• Mutation found in 53% of hereditary hemorragic telangiectasia patients. (PMID:15517393)
• thrombin via PAR1 induced the internalization of endoglin and type-II TGF-beta receptor (TbetaRII) but not type-I receptors in human ECs (PMID:15522964)
• The CD105 expression, as a marker of angiogenesis, was evaluated in myomas obtained after surgery. (PMID:15631865)
• CD105 staining of the microvessels in the adjacent non-tumorous liver tissues is predictive of early recurrence. (PMID:15633211)
• A branch-site mutation leading to abnormal splicing of exon 13 of the endoglin transcript was identified in a child with hereditary hemorrhagic telangiectasia related pulmonary arterial hypertension. (PMID:15687131)
• Extracellular and cytoplasmic domains of the auxiliary TGF-beta receptor endoglin interact with ALK-1 (a type I TGF-beta receptor). Endoglin potentiates TGF-beta/ALK1 signaling. (PMID:15702480)
• A new mutation, c.1844C>T, was found in an Osler-Rendu-Weber patient. (PMID:15712270)
• 6 new mutations were found: 2 nonsense mutations in exons 6 and 8, deletions in exons 5 and 11, and splice site mutations in exon 12 and intron 8. (PMID:15712271)
• Eng is an essential component of the eNOS activation pathway, where it promotes coupling of eNOS activity by facilitating its association with Hsp90. (PMID:15718503)
• endoglin is differentially expressed in human carcinoma and sarcoma cells and its overexpression modulates the proliferative rate of human solid tumour cells (PMID:15809709)
• data show that the expression of endoglin and S100A13 protein corresponds to the activation of the endothelial cells in the process of endometriotic angiogenesis (PMID:15821778)
• These results demonstrate the importance of ACVRL1 and ENG mutations in German hereditary hemorrhagic telangiectasia (HHT) patients displaying mutation frequencies over 80%. (PMID:15880681)
• This comparison of neo-angiogenesis performed by analysing CD105 expression seems to suggest that the biological behaviour of head and neck BSCCs is similar to that of site- and stage-matched conventional SCCs (PMID:15966703)
• endoglin is not associated with intracranial aneurysms (PMID:15976502)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000107130
mus_musculus	Eng	ENSMUSG00000026814
rattus_norvegicus	Eng	ENSRNOG00000050190

Paralogs (2): TGFBR3 (ENSG00000069702), TGFBR3L (ENSG00000260001)

Protein

Protein identifiers

Endoglin — P17813 (reviewed: P17813)

All UniProt accessions (20): P17813, A0AAQ5BH38, A0AAQ5BHA3, A0AAQ5BHA9, A0AAQ5BHC0, A0AAQ5BHC4, A0AAQ5BHE8, A0AAQ5BHF3, A0AAQ5BHF5, A0AAQ5BHF7, A0AAQ5BHG1, A0AAQ5BHG4, A0AAQ5BHG5, A0AAQ5BHG8, A0AAQ5BHH6, A0AAQ5BHI3, A0AAQ5BHI8, A0AAQ5BHM6, F5GX88, Q5T9B9

UniProt curated annotations — full annotation on UniProt →

Function. Vascular endothelium glycoprotein that plays an important role in the regulation of angiogenesis. Required for normal structure and integrity of adult vasculature. Regulates the migration of vascular endothelial cells. Required for normal extraembryonic angiogenesis and for embryonic heart development. May regulate endothelial cell shape changes in response to blood flow, which drive vascular remodeling and establishment of normal vascular morphology during angiogenesis. May play a critical role in the binding of endothelial cells to integrins and/or other RGD receptors. Acts as a TGF-beta coreceptor and is involved in the TGF-beta/BMP signaling cascade that ultimately leads to the activation of SMAD transcription factors. Required for GDF2/BMP9 signaling through SMAD1 in endothelial cells and modulates TGFB1 signaling through SMAD3.

Subunit / interactions. Homodimer; disulfide-linked. Forms a heteromeric complex with the signaling receptors for transforming growth factor-beta: TGFBR1 and/or TGFBR2. It is able to bind TGFB1 and TGFB2 with high affinity, but not TGFB3. Interacts with GDF2, forming a heterotetramer with a 2:2 stoichiometry. Interacts with ACVRL1. Can form a heteromeric complex with GDF2 and ACVRL1. Interacts with BMP10. Interacts with DYNLT4. Interacts with ARRB2.

Subcellular location. Cell membrane.

Tissue specificity. Detected on umbilical veil endothelial cells. Detected in placenta (at protein level). Detected on endothelial cells.

Disease relevance. Telangiectasia, hereditary hemorrhagic, 1 (HHT1) [MIM:187300] A multisystemic vascular dysplasia leading to dilation of permanent blood vessels and arteriovenous malformations of skin, mucosa, and viscera. The disease is characterized by recurrent epistaxis and gastro-intestinal hemorrhage. Visceral involvement includes arteriovenous malformations of the lung, liver, and brain. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The ZP domain mediates dimerization. The N-terminal OR region is composed of two intertwined domains (OR1 and OR2) with a common, novel fold. Each contains 12 beta-strands that form a parallel beta-helix-like structure, plus a single alpha-helix. The OR1 region mediates interaction with GDF2.

Isoforms (2)

UniProt ID	Names	Canonical?
P17813-1	Long	yes
P17813-2	Short

RefSeq proteins (4): NP_000109, NP_001108225, NP_001265067, NP_001393644 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR058899	TGFBR3/Endoglin-like_N	Domain

Pfam: PF26060

UniProt features (138 total): sequence variant 49, strand 36, mutagenesis site 11, disulfide bond 8, region of interest 6, helix 5, glycosylation site 5, turn 4, compositionally biased region 2, modified residue 2, topological domain 2, sequence conflict 2, signal peptide 1, chain 1, short sequence motif 1, transmembrane region 1, splice variant 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5I04	X-RAY DIFFRACTION	2.42
5HZV	X-RAY DIFFRACTION	2.7
5HZW	X-RAY DIFFRACTION	4.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17813-F1	80.84	0.40

Functional residue map

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

Post-translational modifications (2): 646, 649

Disulfide bonds (8): 30–207, 53–182, 242–330, 350–382, 363–442, 394–412, 493–549, 516

Glycosylation sites (5): 88, 102, 121, 134, 307

Mutagenesis-validated functional residues (11):

Position	Phenotype
246	no effect on interaction with gdf2.
269	impairs protein folding, but does not abolish interaction with gdf2.
270–271	loss of interaction with gdf2.
277	no effect on interaction with gdf2.
278	loss of interaction with gdf2.
282	loss of interaction with gdf2.
290	no effect on interaction with gdf2.
350	impairs protein folding. impairs protein folding; when associated with c-382.
382	impairs protein folding. impairs protein folding; when associated with c-350.
516	loss of dimerization via zp domain.
650	loss of interaction with arrb2.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 618 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, MODULE_52, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_CELL_MIGRATION_INVOLVED_IN_HEART_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_OUTFLOW_TRACT_SEPTUM_MORPHOGENESIS, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CELL_CHEMOTAXIS

GO Biological Process (48): negative regulation of transcription by RNA polymerase II (GO:0000122), branching involved in blood vessel morphogenesis (GO:0001569), vasculogenesis (GO:0001570), response to hypoxia (GO:0001666), negative regulation of endothelial cell proliferation (GO:0001937), heart looping (GO:0001947), positive regulation of systemic arterial blood pressure (GO:0003084), outflow tract septum morphogenesis (GO:0003148), epithelial to mesenchymal transition involved in endocardial cushion formation (GO:0003198), endocardial cushion morphogenesis (GO:0003203), cardiac ventricle morphogenesis (GO:0003208), cardiac atrium morphogenesis (GO:0003209), ventricular trabecula myocardium morphogenesis (GO:0003222), cell migration involved in endocardial cushion formation (GO:0003273), regulation of DNA-templated transcription (GO:0006355), cell adhesion (GO:0007155), transforming growth factor beta receptor signaling pathway (GO:0007179), negative regulation of gene expression (GO:0010629), cell migration (GO:0016477), regulation of transforming growth factor beta receptor signaling pathway (GO:0017015), central nervous system vasculogenesis (GO:0022009), extracellular matrix disassembly (GO:0022617), regulation of cell adhesion (GO:0030155), negative regulation of cell migration (GO:0030336), BMP signaling pathway (GO:0030509), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), positive regulation of BMP signaling pathway (GO:0030513), dorsal aorta morphogenesis (GO:0035912), wound healing (GO:0042060), regulation of cell population proliferation (GO:0042127), positive regulation of angiogenesis (GO:0045766), positive regulation of transcription by RNA polymerase II (GO:0045944), smooth muscle tissue development (GO:0048745), artery morphogenesis (GO:0048844), venous blood vessel morphogenesis (GO:0048845), cell motility (GO:0048870), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), atrial cardiac muscle tissue morphogenesis (GO:0055009), cell chemotaxis (GO:0060326), positive regulation of SMAD protein signal transduction (GO:0060391)

GO Molecular Function (13): transmembrane signaling receptor activity (GO:0004888), type II transforming growth factor beta receptor binding (GO:0005114), galactose binding (GO:0005534), glycosaminoglycan binding (GO:0005539), coreceptor activity (GO:0015026), signaling receptor activator activity (GO:0030546), type I transforming growth factor beta receptor binding (GO:0034713), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), activin binding (GO:0048185), transforming growth factor beta binding (GO:0050431), protein binding (GO:0005515), BMP binding (GO:0036122)

GO Cellular Component (9): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), focal adhesion (GO:0005925), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), nuclear body (GO:0016604), signaling receptor complex (GO:0043235), endothelial microparticle (GO:0072563), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signaling receptor activity	3
blood vessel morphogenesis	2
endocardial cushion formation	2
cardiac chamber morphogenesis	2
regulation of gene expression	2
transforming growth factor beta receptor binding	2
cytokine binding	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
angiogenesis	1
branching morphogenesis of an epithelial tube	1
cell differentiation	1
response to stress	1
response to decreased oxygen levels	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
regulation of systemic arterial blood pressure	1
positive regulation of blood pressure	1
outflow tract morphogenesis	1
cardiac septum morphogenesis	1
cardiac epithelial to mesenchymal transition	1
heart morphogenesis	1
endocardial cushion development	1
mesenchyme morphogenesis	1
cardiac ventricle development	1
cardiac atrium development	1
ventricular cardiac muscle tissue morphogenesis	1
heart trabecula morphogenesis	1
cell migration involved in heart development	1
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
cellular process	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
gene expression	1

Protein interactions and networks

STRING

2934 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENG	TGFB1	P01137	997
ENG	ACVRL1	P37023	997
ENG	TGFB3	P10600	993
ENG	TGFBR2	P37173	992
ENG	GDF2	Q9UK05	991
ENG	BMP10	O95393	977
ENG	BMPR2	Q13873	971
ENG	THY1	P04216	941
ENG	NT5E	P21589	923
ENG	CD34	P28906	914
ENG	PTPRC	P08575	909
ENG	GIPC1	O14908	901
ENG	ITGB1	P05556	890
ENG	CD44	P16070	889
ENG	PECAM1	P16284	884
ENG	PGF	P49763	884

IntAct

73 interactions, top by confidence:

A	B	Type	Score
GDF2	ENG	psi-mi:“MI:0407”(direct interaction)	0.660
GDF2	ENG	psi-mi:“MI:0915”(physical association)	0.660
ENG	GDF2	psi-mi:“MI:0915”(physical association)	0.660
ENG	LGALS3	psi-mi:“MI:0407”(direct interaction)	0.630
ENG	LGALS3	psi-mi:“MI:0915”(physical association)	0.630
ENG	LGALS3	psi-mi:“MI:0403”(colocalization)	0.630
ENG	TRIM21	psi-mi:“MI:0915”(physical association)	0.610
ENG	TRIM21	psi-mi:“MI:0407”(direct interaction)	0.610
ENG	TRIM21	psi-mi:“MI:0403”(colocalization)	0.610
ENG	ITGA5	psi-mi:“MI:0915”(physical association)	0.560
ITGA5	ENG	psi-mi:“MI:0915”(physical association)	0.560
ITGA5	ENG	psi-mi:“MI:0403”(colocalization)	0.560
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
ITGB1	ENG	psi-mi:“MI:0915”(physical association)	0.520
ENG	ENG	psi-mi:“MI:0914”(association)	0.500
ENG	ENG	psi-mi:“MI:0915”(physical association)	0.500
ENG	KCNAB1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (229): ACVR2A (Affinity Capture-Western), ENG (Affinity Capture-Western), GDF2 (Reconstituted Complex), ENG (Affinity Capture-MS), LGALS3 (Affinity Capture-Western), ENG (Affinity Capture-Western), ENG (Reconstituted Complex), ENG (Co-localization), ENG (Affinity Capture-Western), ENG (Reconstituted Complex), ENG (Co-localization), CDK1 (Affinity Capture-MS), PDLIM5 (Affinity Capture-MS), SLC25A5 (Affinity Capture-MS), KHSRP (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTW7, A0A1D5NSK0, A0A1L8HYT7, A0A286YEC0, D3ZT86, D3ZWJ9, D4A929, F8W3R9, G7PWZ3, I6M4H4, O08852, O43157, O43278, O75074, O88204, P17813, P49000, P59383, Q04912, Q17R55, Q499Z3, Q4R3B7, Q4TUC0, Q5ND34, Q62190, Q63961, Q6AXX1, Q76MJ5, Q7TN88, Q7TQH7, Q7Z442, Q7Z4F1, Q80W87, Q80YN4, Q866Y3, Q86VZ4, Q8BHW9, Q8BMN4, Q8BYI8, Q8BZT7

Diamond homologs: A0A1Z2R986, P17813, P37176, Q03167, Q63961, O88393, P26342, P35054

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
ERG	“up-regulates quantity by expression”	ENG	“transcriptional regulation”
SP1	“up-regulates quantity by expression”	ENG	“transcriptional regulation”
TGFB1	“up-regulates quantity by expression”	ENG	“transcriptional regulation”
SRC	“down-regulates quantity by destabilization”	ENG	phosphorylation
ENG	“up-regulates activity”	GDF2	binding
ENG	“up-regulates activity”	BMP10	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 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
Signaling by TGFB family members	5	18.0×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
angiogenesis	6	8.7×	6e-03
positive regulation of cell migration	6	8.6×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1995 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	492
Likely pathogenic	102
Uncertain significance	503
Likely benign	602
Benign	41

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1059847	NM_001114753.3(ENG):c.755T>C (p.Ile252Thr)	Pathogenic
1066708	NM_001114753.3(ENG):c.290T>G (p.Leu97Arg)	Pathogenic
1068703	NM_001114753.3(ENG):c.767_786del (p.Pro256fs)	Pathogenic
1068858	NC_000009.11:g.(?130577951)(130582326_?)del	Pathogenic
1070889	NM_001114753.3(ENG):c.657_658del (p.Ile220fs)	Pathogenic
1073414	NM_001114753.3(ENG):c.654_655del (p.Ile220fs)	Pathogenic
1073561	NM_001114753.3(ENG):c.375_378dup (p.Phe127fs)	Pathogenic
1074391	NM_001114753.3(ENG):c.1134G>C (p.Ala378=)	Pathogenic
1074831	NM_001114753.3(ENG):c.1687-2A>G	Pathogenic
1074832	NM_001114753.3(ENG):c.1426C>T (p.Gln476Ter)	Pathogenic
1075363	NM_001114753.3(ENG):c.690-1G>C	Pathogenic
1075836	NM_001114753.3(ENG):c.1531del (p.Ala511fs)	Pathogenic
1076004	NM_001114753.3(ENG):c.863_867dup (p.Phe290fs)	Pathogenic
1076795	NM_001114753.3(ENG):c.1687G>T (p.Glu563Ter)	Pathogenic
1076878	NC_000009.11:g.(?130605351)(130616761_?)del	Pathogenic
1076879	NC_000009.11:g.(?130577951)(130581121_?)del	Pathogenic
1076880	NC_000009.11:g.(?_130578090)_130581774del	Pathogenic
1076881	NC_000009.11:g.(?130578196)(130592116_?)del	Pathogenic
1076882	NC_000009.11:g.(?130587069)(130592116_?)del	Pathogenic
1076907	NM_001114753.3(ENG):c.360+1G>C	Pathogenic
1076967	NM_001114753.3(ENG):c.405dup (p.Thr136fs)	Pathogenic
1120155	Single allele	Pathogenic
1120156	Single allele	Pathogenic
1120157	Single allele	Pathogenic
1120158	Single allele	Pathogenic
1163504	NM_001114753.3(ENG):c.397dup (p.Val133fs)	Pathogenic
1163505	NM_001114753.3(ENG):c.132_133del (p.Thr45fs)	Pathogenic
1330266	NM_001114753.3(ENG):c.524-1G>A	Pathogenic
1330389	NM_001114753.3(ENG):c.558del (p.Ser187fs)	Pathogenic
1330982	NM_001114753.3(ENG):c.465dup (p.Ile156fs)	Pathogenic

SpliceAI

2573 predictions. Top by Δscore:

Variant	Effect	Δscore
9:127813192:CA:C	acceptor_loss	1.0000
9:127813193:A:AG	acceptor_gain	1.0000
9:127813193:A:AT	acceptor_loss	1.0000
9:127813194:G:GA	acceptor_gain	1.0000
9:127813194:GA:G	acceptor_gain	1.0000
9:127813194:GAC:G	acceptor_gain	1.0000
9:127813194:GACC:G	acceptor_gain	1.0000
9:127813194:GACCA:G	acceptor_gain	1.0000
9:127815804:AACCT:A	acceptor_loss	1.0000
9:127815937:ACT:A	donor_loss	1.0000
9:127815938:CTC:C	donor_loss	1.0000
9:127815939:TCA:T	donor_loss	1.0000
9:127815940:CACGC:C	donor_loss	1.0000
9:127815941:A:AC	donor_gain	1.0000
9:127815941:ACG:A	donor_gain	1.0000
9:127815941:ACGCG:A	donor_loss	1.0000
9:127815942:C:CA	donor_loss	1.0000
9:127815942:C:CC	donor_gain	1.0000
9:127815942:CG:C	donor_gain	1.0000
9:127815942:CGC:C	donor_gain	1.0000
9:127815942:CGCG:C	donor_gain	1.0000
9:127815942:CGCGT:C	donor_gain	1.0000
9:127816049:GCAAC:G	acceptor_gain	1.0000
9:127816050:CAAC:C	acceptor_gain	1.0000
9:127816050:CAACC:C	acceptor_gain	1.0000
9:127816051:AAC:A	acceptor_gain	1.0000
9:127816051:AACC:A	acceptor_loss	1.0000
9:127816052:AC:A	acceptor_gain	1.0000
9:127816053:CC:C	acceptor_gain	1.0000
9:127816053:CCTAG:C	acceptor_loss	1.0000

AlphaMissense

4281 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:127815712:G:C	S649R	0.993
9:127815712:G:T	S649R	0.993
9:127815714:T:G	S649R	0.993
9:127815730:G:C	S643R	0.992
9:127815730:G:T	S643R	0.992
9:127815732:T:G	S643R	0.992
9:127825266:A:G	W261R	0.992
9:127825266:A:T	W261R	0.992
9:127815691:G:C	S656R	0.991
9:127815691:G:T	S656R	0.991
9:127815693:T:G	S656R	0.991
9:127815694:G:C	S655R	0.991
9:127815694:G:T	S655R	0.991
9:127815696:T:G	S655R	0.991
9:127818217:A:G	F530S	0.991
9:127815721:G:C	S646R	0.990
9:127815721:G:T	S646R	0.990
9:127815723:T:G	S646R	0.990
9:127820027:C:G	C382S	0.989
9:127820028:A:T	C382S	0.989
9:127818160:C:G	C549S	0.988
9:127818161:A:T	C549S	0.988
9:127818328:C:G	C493S	0.988
9:127818329:A:T	C493S	0.988
9:127815742:G:C	S639R	0.987
9:127815742:G:T	S639R	0.987
9:127815744:T:G	S639R	0.987
9:127825264:C:A	W261C	0.987
9:127825264:C:G	W261C	0.987
9:127818161:A:G	C549R	0.986

dbSNP variants (sampled 300 via entrez): RS1000043958 (9:127831544 T>C), RS1000077010 (9:127828309 G>A,C), RS1000255173 (9:127822472 T>A), RS1000307295 (9:127853063 G>T), RS1000397732 (9:127856320 G>A), RS1000409035 (9:127856608 G>A), RS1000430042 (9:127828564 C>T), RS1000465559 (9:127817687 T>C), RS1000488055 (9:127836018 T>A), RS1000589360 (9:127824079 A>C,G), RS1000620593 (9:127824231 C>T), RS1000656118 (9:127830403 G>T), RS1000698349 (9:127841027 T>C), RS1000834647 (9:127817387 C>T), RS1000846307 (9:127845979 A>G)

Disease associations

OMIM: gene MIM:131195 | disease phenotypes: MIM:187300, MIM:174900, MIM:251300, MIM:178600, MIM:607151, MIM:152700, MIM:601744, MIM:108010

GenCC curated gene-disease

Disease	Classification	Inheritance
telangiectasia, hereditary hemorrhagic, type 1	Definitive	Autosomal dominant
hereditary hemorrhagic telangiectasia	Strong	Autosomal dominant
juvenile polyposis syndrome	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
juvenile polyposis syndrome	Limited	AD
telangiectasia, hereditary hemorrhagic, type 1	Definitive	AD

Mondo (9): hereditary hemorrhagic telangiectasia (MONDO:0019180), telangiectasia, hereditary hemorrhagic, type 1 (MONDO:0008535), juvenile polyposis syndrome (MONDO:0017380), Galloway-Mowat syndrome 1 (MONDO:0033005), pulmonary hypertension, primary, 1 (MONDO:0024533), pulmonary arterial hypertension (MONDO:0015924), Moyamoya disease 2 (MONDO:0011784), systemic lupus erythematosus (MONDO:0007915), arteriovenous malformations of the brain (MONDO:0007154)

Orphanet (10): Hereditary hemorrhagic telangiectasia (Orphanet:774), Juvenile polyposis syndrome (Orphanet:2929), Galloway-Mowat syndrome (Orphanet:2065), CAMOS syndrome (Orphanet:83472), Idiopathic/heritable pulmonary arterial hypertension (Orphanet:422), Pulmonary arterial hypertension (Orphanet:182090), Pulmonary arterial hypertension associated with congenital heart disease (Orphanet:275803), Moyamoya disease (Orphanet:2573), Systemic lupus erythematosus (Orphanet:536), Brain arteriovenous malformation (Orphanet:46724)

HPO phenotypes

89 total (30 of 89 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000214	Lip telangiectasia
HP:0000227	Tongue telangiectasia
HP:0000421	Epistaxis
HP:0000434	Nasal mucosa telangiectasia
HP:0000471	Gastrointestinal angiodysplasia
HP:0000524	Conjunctival telangiectasia
HP:0000822	Hypertension
HP:0000961	Cyanosis
HP:0000969	Edema
HP:0001009	Telangiectasia
HP:0001017	Anemic pallor
HP:0001123	Visual field defect
HP:0001217	Clubbing
HP:0001232	Nail bed telangiectasia
HP:0001250	Seizure
HP:0001269	Hemiparesis
HP:0001342	Cerebral hemorrhage
HP:0001394	Cirrhosis
HP:0001399	Hepatic failure
HP:0001409	Portal hypertension
HP:0001510	Growth delay
HP:0001635	Congestive heart failure
HP:0001694	Right-to-left shunt
HP:0001722	High-output congestive heart failure
HP:0001892	Abnormal bleeding
HP:0001901	Polycythemia
HP:0001903	Anemia
HP:0002040	Esophageal varix
HP:0002076	Migraine

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000753_14	Metabolic syndrome	1.000000e-06
GCST005951_65	Body mass index	5.000000e-09
GCST006585_2846	Blood protein levels	8.000000e-09
GCST90002393_316	Monocyte count	6.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0000195	metabolic syndrome
EFO:0006336	diastolic blood pressure
EFO:0004340	body mass index
EFO:0005091	monocyte count

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D002538	Intracranial Arteriovenous Malformations	C10.228.140.300.520; C10.500.190.500; C14.240.850.750.295; C14.240.850.875.500; C14.907.150.295; C14.907.253.560.400; C16.131.240.850.750.295; C16.131.240.850.875.500; C16.131.666.190.500
D008180	Lupus Erythematosus, Systemic	C17.300.480; C20.111.590
D000081029	Pulmonary Arterial Hypertension	C08.381.423.847
D013683	Telangiectasia, Hereditary Hemorrhagic	C14.907.454.900; C14.907.823.780; C15.378.463.515.900; C16.131.240.850.968
C536992	Moyamoya disease 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3712885 (SINGLE PROTEIN)

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4451422	ENG, FPGS		0.00	0
rs1800956	ENG		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — CD molecules

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

Ligand	Action	Affinity	Parameter
carotuximab	Binding	9.0	pKd

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Cadmium	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
Raloxifene Hydrochloride	increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
napabucasin	decreases expression	1
mivebresib	decreases expression	1
dicrotophos	increases expression	1
testosterone enanthate	affects expression	1
bisphenol A	increases expression	1
deoxynivalenol	decreases expression	1
salinomycin	decreases expression	1
hydroxyhydroquinone	decreases expression, decreases reaction	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium bichromate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
perfluorooctanoic acid	decreases expression	1
tobacco tar	decreases expression, decreases reaction	1
benzo(e)pyrene	increases methylation	1
4-aminobenzhydrazide	decreases expression, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
Y 27632	decreases expression	1
3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1

Cellosaurus cell lines

9 cell lines: 6 transformed cell line, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1R9	Abcam HeLa ENG KO	Cancer cell line	Female
CVCL_B9XR	Abcam THP-1 ENG KO	Cancer cell line	Male
CVCL_C6ZL	Abcam PC-3 ENG KO	Cancer cell line	Male
CVCL_GT60	GM10232	Transformed cell line	Male
CVCL_W903	GM10228	Transformed cell line	Male
CVCL_W904	GM10231	Transformed cell line	Female
CVCL_W905	GM10249	Transformed cell line	Male
CVCL_W906	GM10711	Transformed cell line	Female
CVCL_W907	GM10715	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05421312	PHASE4	UNKNOWN	Periarticular Penetration of Cefazolin and Clindamycin in Second Stage Revision Arthroplasty of the Hip
NCT02389959	PHASE4	COMPLETED	Intranasal Bevacizumab for HHT-Related Epistaxis
NCT00058929	PHASE4	COMPLETED	A Transition Study From Flolan® to Remodulin® in Patients With Pulmonary Arterial Hypertension
NCT00303459	PHASE4	COMPLETED	Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH)
NCT00323297	PHASE4	COMPLETED	Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension
NCT00367770	PHASE4	COMPLETED	BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology
NCT00403650	PHASE4	COMPLETED	Inhaled Iloprost for Sarcoidosis-associated Pulmonary Hypertension
NCT00430716	PHASE4	TERMINATED	To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.
NCT00433329	PHASE4	COMPLETED	Combination Therapy in Pulmonary Arterial Hypertension
NCT00439946	PHASE4	TERMINATED	Safety, Efficacy, and Treatment Satisfaction Switching From Flolan to Remodulin Using the Crono Five Ambulatory Pump in Patients With PAH
NCT00483626	PHASE4	UNKNOWN	Hemodynamic Response After Six Months of Sildenafil
NCT00494533	PHASE4	TERMINATED	Study of Intravenous Remodulin in Patients in India With Pulmonary Arterial Hypertension
NCT00617305	PHASE4	COMPLETED	Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)
NCT00625079	PHASE4	WITHDRAWN	Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil
NCT00625469	PHASE4	WITHDRAWN	Pulmonary Arterial Hypertension Secondary to Idiopathic Pulmonary Fibrosis and Treatment With Bosentan
NCT00705588	PHASE4	UNKNOWN	Long Acting Phosphodiesterase 5 Inhibitors as Add-on Therapy for Patients With Pulmonary Hypertension Treated With Prostanoids.
NCT00741819	PHASE4	COMPLETED	Safety Evaluation of Inhaled Treprostinil Administration Following Transition From Inhaled Ventavis in Pulmonary Arterial Hypertension (PAH) Subjects
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT01105091	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension
NCT01105117	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension - Extension of AC-066A401
NCT01268553	PHASE4	COMPLETED	Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication
NCT01302444	PHASE4	TERMINATED	Treprostinil Combined With Tadalafil for Pulmonary Hypertension
NCT01330108	PHASE4	COMPLETED	Safely Change From Bosentan to Ambrisentan in Pulmonary Hypertension
NCT01433328	PHASE4	TERMINATED	Lidocaine Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01508780	PHASE4	WITHDRAWN	Combined Use of Angiography, Optical Coherence Tomography and Intravascular Ultrasound in Evaluation of Pulmonary Vascular Structure and Function in Patients With Pulmonary Arterial Hypertension Treated With Oral Bosentan
NCT01615627	PHASE4	WITHDRAWN	Hypotonic Treprostinil Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01642407	PHASE4	COMPLETED	Safety And Efficacy Of Sildenafil In Children With Pulmonary Arterial Hypertension
NCT01649739	PHASE4	UNKNOWN	Vardenafil as add-on Therapy for Patients With Pulmonary Hypertension Treated With Inhaled Iloprost
NCT02060487	PHASE4	TERMINATED	Effects of Oral Sildenafil on Mortality in Adults With PAH
NCT02253394	PHASE4	TERMINATED	The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study
NCT02284737	PHASE4	TERMINATED	A Study to Investigate the Efficacy of PADN to Improved Functional Capacity and Hemodynamics in Patients With PAH
NCT02310672	PHASE4	COMPLETED	REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension
NCT02847260	PHASE4	COMPLETED	Safety and Tolerability of Rapid Dose Titration of Subcutaneous Remodulin® Therapy in PAH Subjects (RAPID)
NCT02882126	PHASE4	WITHDRAWN	An Open Label Extension Study to Evaluate the Safety of Continued Therapy of Subcutanous Remodulin® in Pulmonary Arterial Hypertension
NCT02885012	PHASE4	TERMINATED	Crossover Study From Macitentan or Bosentan Over to Ambrisentan
NCT02891850	PHASE4	COMPLETED	Riociguat rEplacing PDE-5i Therapy evaLuated Against Continued PDE-5i thErapy
NCT02893995	PHASE4	WITHDRAWN	Safety, Tolerability, Pharmacokinetics and Efficacy of Two Different Rates of Subcutanous Remodulin® Dose Titration in Pulmonary Arterial Hypertension
NCT02968901	PHASE4	TERMINATED	Clinical Study Evaluating the Effects of First-line Oral cOmbination theraPy of maciTentan and tadalafIl in Patients With Newly Diagnosed pulMonary Arterial Hypertension (OPTIMA)
NCT03055221	PHASE4	COMPLETED	TRUST-2: Safety and Efficacy of Intravenous Remodulin® in Patients in India With Pulmonary Arterial Hypertension (PAH)
NCT03078907	PHASE4	COMPLETED	Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension.