Heritable Pulmonary Arterial Hypertension disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

MCID: HRT015 MIFTS: 48	Heritable Pulmonary Arterial Hypertension Categories: Respiratory diseases, Rare diseases, Genetic diseases
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Aliases & Classifications for Heritable Pulmonary Arterial Hypertension

MalaCards integrated aliases for Heritable Pulmonary Arterial Hypertension:

Name: Heritable Pulmonary Arterial Hypertension ²⁴ ⁵⁹

Hereditary Pulmonary Arterial Hypertension ⁵⁹

Familial Pulmonary Arterial Hypertension ⁵⁹

Familial Primary Pulmonary Hypertension ⁷³

Fpah ⁵⁹

Hpah ⁵⁹

Characteristics:

Orphanet epidemiological data:

⁵⁹

heritable pulmonary arterial hypertension
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Europe),<1/1000000 (France),1-9/1000000 (Czech Republic); Age of onset: All ages; Age of death: any age;

GeneReviews:

²⁴

Penetrance Penetrance (i.e., the presence of symptoms in an individual with a bmpr2 pathogenic variant) is 20% [newman et al 2001]...

Classifications:

MalaCards categories:
Global: Rare diseases Genetic diseases
Anatomical: Respiratory diseases

See all MalaCards categories (disease lists)

ICD10: ³⁴

Diseases of the circulatory system

Pulmonary heart disease and diseases of pulmonary circulation

Other pulmonary heart diseases

Primary pulmonary hypertension

Orphanet: ⁵⁹

Rare respiratory diseases

External Ids:

Orphanet ⁵⁹ ORPHA275777

UMLS via Orphanet ⁷⁴ C0340543 C1701939

ICD10 via Orphanet ³⁴ I27.0

UMLS ⁷³ C0340543

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Summaries for Heritable Pulmonary Arterial Hypertension

MalaCards based summary : Heritable Pulmonary Arterial Hypertension, also known as hereditary pulmonary arterial hypertension, is related to pulmonary hypertension, primary, 1 and familial pulmonary arterial hypertension leucopenia and atrial septal defect. An important gene associated with Heritable Pulmonary Arterial Hypertension is BMPR2 (Bone Morphogenetic Protein Receptor Type 2), and among its related pathways/superpathways are BMP Pathway and Human Embryonic Stem Cell Pluripotency. The drugs Adempas and Spironolactone have been mentioned in the context of this disorder. Affiliated tissues include heart, lung and testes, and related phenotypes are Increased shRNA abundance (Z-score > 2) and Increased shRNA abundance (Z-score > 2)

GeneReviews: NBK1485

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Related Diseases for Heritable Pulmonary Arterial Hypertension

Diseases related to Heritable Pulmonary Arterial Hypertension via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 26)

#	Related Disease	Score	Top Affiliating Genes
1	pulmonary hypertension, primary, 1	31.0	ACVRL1 BMPR2 ENG KCNK3
2	familial pulmonary arterial hypertension leucopenia and atrial septal defect	12.2
3	idiopathic and/or familial pulmonary arterial hypertension	12.2
4	eisenmenger syndrome	10.5	BMPR2 TGFB1
5	pulmonary venoocclusive disease 1, autosomal dominant	10.3	BMPR2 EIF2AK4
6	chronic pulmonary heart disease	10.2	ACVRL1 BMPR2
7	eosinophilic variant of chromophobe renal cell carcinoma	10.1	CAV1 TGFB1
8	mixed connective tissue disease	10.1	ACVRL1 BMPR2
9	bone fracture	10.0	CAV1 TGFB1
10	iron metabolism disease	9.8
11	retinitis	9.8
12	connective tissue disease	9.8
13	central serous chorioretinopathy	9.8
14	aneurysm	9.8
15	telangiectasia, hereditary hemorrhagic, type 1	9.7	ACVRL1 ENG
16	pulmonary arteriovenous malformation	9.7	ACVRL1 ENG
17	angiodysplasia	9.6	ACVRL1 ENG
18	weber syndrome	9.6	ACVRL1 ENG
19	telangiectasis	9.4	ACVRL1 BMPR2 ENG
20	arteriovenous malformations of the brain	9.3	ACVRL1 ENG
21	arteriovenous malformation	9.3	ACVRL1 BMPR2 ENG
22	juvenile polyposis syndrome	9.3	ENG SMAD9
23	pulmonary venoocclusive disease	9.3	ACVRL1 BMPR2 EIF2AK4 KCNK3
24	vascular disease	9.1	ACVRL1 BMPR2 ENG
25	hereditary hemorrhagic telangiectasia	9.0	ACVRL1 ENG
26	pulmonary hypertension	6.6	ACVRL1 BMPR2 CAV1 EIF2AK4 ENG KCNK3

Graphical network of the top 20 diseases related to Heritable Pulmonary Arterial Hypertension:

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Symptoms & Phenotypes for Heritable Pulmonary Arterial Hypertension

GenomeRNAi Phenotypes related to Heritable Pulmonary Arterial Hypertension according to GeneCards Suite gene sharing:

²⁶ (show all 14)

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Increased shRNA abundance (Z-score > 2)	GR00366-A-113	9.89	TBX4 ACVRL1 BMPR2
2	Increased shRNA abundance (Z-score > 2)	GR00366-A-130	9.89	ACVRL1
3	Increased shRNA abundance (Z-score > 2)	GR00366-A-140	9.89	TBX4
4	Increased shRNA abundance (Z-score > 2)	GR00366-A-168	9.89	ACVRL1
5	Increased shRNA abundance (Z-score > 2)	GR00366-A-199	9.89	ACVRL1
6	Increased shRNA abundance (Z-score > 2)	GR00366-A-24	9.89	BMPR2
7	Increased shRNA abundance (Z-score > 2)	GR00366-A-43	9.89	ACVRL1
8	Increased shRNA abundance (Z-score > 2)	GR00366-A-49	9.89	BMPR2
9	Increased shRNA abundance (Z-score > 2)	GR00366-A-63	9.89	TBX4 ACVRL1
10	Increased shRNA abundance (Z-score > 2)	GR00366-A-73	9.89	ACVRL1
11	Increased shRNA abundance (Z-score > 2)	GR00366-A-80	9.89	BMPR2
12	Increased shRNA abundance (Z-score > 2)	GR00366-A-81	9.89	ACVRL1
13	Increased shRNA abundance (Z-score > 2)	GR00366-A-85	9.89	ACVRL1 BMPR2
14	Reduced mammosphere formation	GR00396-S	9.02	BMPR2 CAV1 EIF2AK4 KCNK3 TGFB1

MGI Mouse Phenotypes related to Heritable Pulmonary Arterial Hypertension:

⁴⁶ (show all 14)

#	Description	MGI Source Accession	Score	Top Affiliating Genes
1	cardiovascular system	MP:0005385	10.18	CAV1 ENG KCNK3 KLF2 SMAD9 TBX4
2	behavior/neurological	MP:0005386	10.14	ACVRL1 BMPR2 CAV1 EIF2AK4 ENG KCNK3
3	growth/size/body region	MP:0005378	10.13	ACVRL1 BMPR2 CAV1 EIF2AK4 ENG KLF2
4	homeostasis/metabolism	MP:0005376	10.09	ACVRL1 BMPR2 CAV1 EIF2AK4 ENG KCNK3
5	embryo	MP:0005380	10.04	SMAD9 TBX4 TGFB1 ACVRL1 BMPR2 ENG
6	mortality/aging	MP:0010768	10.02	ACVRL1 BMPR2 CAV1 EIF2AK4 ENG KLF2
7	hematopoietic system	MP:0005397	10	ACVRL1 BMPR2 CAV1 EIF2AK4 ENG KLF2
8	muscle	MP:0005369	9.92	ACVRL1 BMPR2 CAV1 EIF2AK4 ENG KLF2
9	craniofacial	MP:0005382	9.91	ACVRL1 ENG KLF2 SMAD9 TGFB1
10	nervous system	MP:0003631	9.91	ACVRL1 BMPR2 CAV1 EIF2AK4 ENG KCNK3
11	liver/biliary system	MP:0005370	9.8	EIF2AK4 KLF2 TGFB1 ACVRL1 CAV1
12	normal	MP:0002873	9.7	ACVRL1 BMPR2 ENG KCNK3 KLF2 SMAD9
13	respiratory system	MP:0005388	9.56	ACVRL1 BMPR2 CAV1 ENG KCNK3 KLF2
14	skeleton	MP:0005390	9.1	BMPR2 CAV1 KLF2 SMAD9 TBX4 TGFB1

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Drugs & Therapeutics for Heritable Pulmonary Arterial Hypertension

FDA approved drugs:

#	Drug Name	Active Ingredient(s) ¹⁸	Company	Approval Date
1	Adempas ¹⁸	RIOCIGUAT	Bayer Healthcare Pharmaceuticals	October 2013
FDA Label: Adempas Disease/s that Drug Treats:Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Arterial Hypertension Indications and Usage: ¹⁸ Adempas is a soluble guanylate cyclase (sGC) stimulator indicated for the treatment of adults with: * Persistent/recurrent Chronic Thromboembolic Pulmonary Hypertension (CTEPH) (WHO Group 4) after surgical treatment or inoperable CTEPH to improve exercise capacity and WHO functional class. (1.1) * Pulmonary Arterial Hypertension (PAH) (WHO Group 1) to improve exercise capacity, improve WHO functional class and to delay clinical worsening. (1.2) DrugBank Targets: - Mechanism of Action: ¹⁸ Target: soluble guanylate cyclase (sGC) Action: stimulator FDA: Riociguat is a stimulator of soluble guanylate cyclase (sGC), an enzyme in the cardiopulmonary system and the receptor for nitric oxide (NO). When NO binds to sGC, the enzyme catalyzes synthesis of the signaling molecule cyclic guanosine monophosphate (cGMP). Intracellular cGMP plays an important role in regulating processes that influence vascular tone, proliferation, fibrosis and inflammation.Pulmonary hypertension is associated with endothelial dysfunction, impaired synthesis of nitric oxide and insufficient stimulation of the NO-sGC-cGMP pathway. Riociguat has a dual mode of action. It sensitizes sGC to endogenous NO by stabilizing the NO-sGC binding. Riociguat also directly stimulates sGC via a different binding site, independently of NO. Riociguat stimulates the NO-sGC-cGMP pathway and leads to increased generation of cGMP with subsequent vasodilation. The active metabolite (M1) of riociguat is 1/3 to 1/10 as potent as riociguat.

Drugs for Heritable Pulmonary Arterial Hypertension (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 301)

Name

Status

Phase

Clinical Trials

Cas Number

PubChem Id

Spironolactone

Approved

Phase 4,Phase 1,Phase 2,Not Applicable

1952-01-7, 52-01-7

5833

Iron

Approved

Phase 4,Phase 2,Not Applicable

7439-89-6

23925

Treprostinil

Approved, Investigational

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable

81846-19-7

54786 6918140

Bosentan

Approved, Investigational

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable,Early Phase 1

147536-97-8

104865

Iloprost

Approved, Investigational

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable

78919-13-8

6443959

Tadalafil

Approved, Investigational

Phase 4,Phase 3,Phase 1,Phase 2

171596-29-5

110635

Macitentan

Approved

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable

441798-33-0

Epoprostenol

Approved

Phase 4,Phase 3,Phase 2,Not Applicable

61849-14-7, 35121-78-9

5280427 5282411

Silver sulfadiazine

Approved, Vet_approved

Phase 4

22199-08-2

441244

Clevidipine

Approved, Investigational

Phase 4

167221-71-8

Selexipag

Approved

Phase 4,Phase 3,Phase 2

475086-01-2

Lidocaine

Approved, Vet_approved

Phase 4

137-58-6

3676

Citric Acid

Approved, Nutraceutical, Vet_approved

Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable

77-92-9

311

Tezosentan

Investigational

Phase 4,Phase 3,Phase 2,Not Applicable

180384-57-0

Sildenafil Citrate

Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable

171599-83-0

calcium channel blockers

Phase 4,Phase 1,Not Applicable

diuretics

Phase 4,Phase 1,Phase 2,Not Applicable

Micronutrients

Phase 4,Phase 2,Phase 1,Not Applicable

Chelating Agents

Phase 4,Phase 2,Phase 3,Not Applicable

Mineralocorticoid Receptor Antagonists

Phase 4,Phase 1,Phase 2,Not Applicable

Mineralocorticoids

Phase 4,Phase 1,Phase 2,Not Applicable

Natriuretic Agents

Phase 4,Phase 1,Phase 2,Not Applicable

Sodium Channel Blockers

Phase 4,Phase 3,Phase 1

Hormone Antagonists

Phase 4,Phase 2,Phase 1,Not Applicable

Trace Elements

Phase 4,Phase 2,Phase 1,Not Applicable

Hormones

Phase 4,Phase 2,Phase 1,Not Applicable

Diuretics, Potassium Sparing

Phase 4,Phase 3,Phase 1,Phase 2,Not Applicable

Vardenafil Dihydrochloride

Phase 4,Phase 3

Hormones, Hormone Substitutes, and Hormone Antagonists

Phase 4,Phase 2,Phase 1,Not Applicable

Vasodilator Agents

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable,Early Phase 1

Endothelin A Receptor Antagonists

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable

Endothelin Receptor Antagonists

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable,Early Phase 1

Peripheral Nervous System Agents

Phase 4,Phase 2,Phase 3,Phase 1,Early Phase 1

Pharmaceutical Solutions

Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable

Phosphodiesterase 5 Inhibitors

Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable

Phosphodiesterase Inhibitors

Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable

Antihypertensive Agents

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable,Early Phase 1

Platelet Aggregation Inhibitors

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable

Anticoagulants

Phase 4,Phase 2,Phase 3,Not Applicable

Calcium, Dietary

Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable

Anti-Arrhythmia Agents

Phase 4,Phase 2,Phase 1

Liver Extracts

Phase 4,Phase 2

Central Nervous System Depressants

Phase 4,Phase 2

Natriuretic Peptide, Brain

Phase 4

Anesthetics

Phase 4,Phase 2

Anesthetics, Local

Phase 4

Citrate

Nutraceutical

Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable

Calamus

Nutraceutical

Phase 4,Phase 3,Phase 2

Nitric Oxide

Approved

Phase 3,Phase 2,Phase 1,Not Applicable,Early Phase 1

10102-43-9

145068 160954

Ranolazine

Approved, Investigational

Phase 3,Phase 1

142387-99-3, 95635-55-5

56959

Interventional clinical trials:

(show top 50) (show all 553)

#	Name	Status	NCT ID	Phase	Drugs
1	Effect of BMPR-2 Gene Mutations on Hemodynamic Response by Iloprost Inhalation in Pulmonary Arterial Hypertension	Unknown status	NCT01054105	Phase 4	Iloprost
2	Iron Deficiency In Pulmonary Hypertension	Unknown status	NCT01288651	Phase 4	Ferricarboxymaltose
3	Hemodynamic Response After Six Months of Sildenafil	Unknown status	NCT00483626	Phase 4	oral sildenafil
4	Effects of Spironolactone on Collagen Metabolism in Patients With Pulmonary Arterial Hypertension	Unknown status	NCT01468571	Phase 4	Spironolactone;Placebo
5	Long Acting Phosphodiesterase 5 Inhibitors as Add-on Therapy for Patients With Pulmonary Hypertension Treated With Prostanoids.	Unknown status	NCT00705588	Phase 4	Tadalafil;Vardenafil
6	Vardenafil as add-on Therapy for Patients With Pulmonary Hypertension Treated With Inhaled Iloprost	Unknown status	NCT01649739	Phase 4	Levitra
7	Hypotonic Treprostinil Subcutaneous Infusion for Control of Treprostinil Related Site Pain	Unknown status	NCT01615627	Phase 4	HypotonicTreprostinil Solution;Eutonic Treprostinil Solution
8	Acute Effect of Sildenafil on Exercise Tolerance and Functional Capacity in COPD, IPF and Post Pneumonectomy Patients	Unknown status	NCT01382368	Phase 4	Sildenafil
9	Epoprostenol for Injection in Pulmonary Arterial Hypertension - Extension of AC-066A401	Completed	NCT01105117	Phase 4	ACT-385781A (Actelion Epoprostenol);Flolan®
10	Epoprostenol for Injection in Pulmonary Arterial Hypertension	Completed	NCT01105091	Phase 4	ACT-385781A (Actelion Epoprostenol);Flolan®
11	An Open-Label Uncontrolled Study of the Safety and Efficacy of Ambrisentan in Participants With Exercise-Induced Pulmonary Arterial Hypertension (PAH)	Completed	NCT01338636	Phase 4	Ambrisentan
12	Effects of Tracleer (Bosentan) on Pulmonary Arterial Hypertension Related to Eisenmenger Physiology	Completed	NCT00317486	Phase 4	bosentan
13	TRUST-2: Safety and Efficacy of Intravenous Remodulin® in Patients in India With Pulmonary Arterial Hypertension (PAH)	Completed	NCT03055221	Phase 4	Intravenous Treprostinil
14	Safety And Efficacy Of Sildenafil In Children With Pulmonary Arterial Hypertension	Completed	NCT01642407	Phase 4	Sildenafil
15	Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)	Completed	NCT00617305	Phase 4	Ambrisentan;Placebo;Sildenafil;Tadalafil
16	Safety Evaluation of Inhaled Treprostinil Administration Following Transition From Inhaled Ventavis in Pulmonary Arterial Hypertension (PAH) Subjects	Completed	NCT00741819	Phase 4	Inhaled treprostinil
17	Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH)	Completed	NCT00303459	Phase 4	bosentan;placebo
18	A Transition Study From Flolan® to Remodulin® in Patients With Pulmonary Arterial Hypertension	Completed	NCT00058929	Phase 4	treprostinil sodium
19	Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension	Completed	NCT00323297	Phase 4	Bosentan;Bosentan;Sildenafil Citrate
20	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis	Completed	NCT01042158	Phase 4	tadalafil and ambrisentan upfront combination therapy
21	Combination Therapy in Pulmonary Arterial Hypertension	Completed	NCT00433329	Phase 4	Bosentan;Sildenafil
22	BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology	Completed	NCT00367770	Phase 4	Tracleer®
23	Study of a New Thermo Stable Formulation of Epoprostenol Sodium to Treat Pulmonary Arterial Hypertension (PAH)	Completed	NCT01462565	Phase 4	current marketed FLOLAN (epoprostenol sodium);new thermo stable formulation of epoprostenol sodium
24	Safely Change From Bosentan to Ambrisentan in Pulmonary Hypertension	Completed	NCT01330108	Phase 4	ambrisentan
25	Measuring Outcomes In Patients With Pulmonary Arterial Hypertension Not on Active Treatment (MOTION)	Completed	NCT02191137	Phase 4	Riociguat (Adempas, BAY63-2521)
26	Bosentan in Treatment of Pulmonary Arterial Hypertension	Completed	NCT00266162	Phase 4	Bosentan administration
27	Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication	Completed	NCT01268553	Phase 4	Treprostinil
28	Safety and Tolerability of Rapid Dose Titration of Subcutaneous Remodulin® Therapy in PAH Subjects (RAPID)	Completed	NCT02847260	Phase 4	Remodulin
29	Phase IV Study of Chronic Infusional Epoprostenol for Severe Primary Pulmonary Hypertension	Completed	NCT00004754	Phase 4	epoprostenol
30	Inhaled Iloprost for Sarcoidosis-associated Pulmonary Hypertension	Completed	NCT00403650	Phase 4	Iloprost
31	The Effect of Tracleer® on Male Fertility	Completed	NCT00082186	Phase 4	bosentan
32	Pulmonary Artery Remodelling With Bosentan	Completed	NCT00595049	Phase 4	bosentan
33	Evaluation of a New Thermostable Formulation of FLOLAN in Japanese Subjects	Completed	NCT02705807	Phase 4	FLOLAN injection with currently marketed diluent;FLOLAN injection with reformulated diluent
34	Efficacy of Beraprost in Lowering Pulmonary Arterial Pressure in Children	Completed	NCT03431649	Phase 4	Beraprost Sodium;Sildenafil Citrate
35	A 48-week Study of the Effect of Dual Therapy (Inhaled Treprostinil and Tadafafil) Versus Monotherapy (Tadalafil).	Completed	NCT01305252	Phase 4	treprostinil inhalations;tadalafil
36	Safety, Efficacy and Treatment Satisfaction in Patients With PAH Rapidly Switched From Epoprostenol to Remodulin	Completed	NCT00373360	Phase 4	treprostinil sodium
37	Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan	Completed	NCT01051960	Phase 4	Ambrisentan
38	Study of Sildenafil Effects in Combination With Rehabilitation in Patients With Chronic Obstructive Pulmonary Disease (COPD) and Associated Pulmonary Hypertension	Completed	NCT01055405	Phase 4	Sildenafil
39	Clevidipine for Vasoreactivity Evaluation of the Pulmonary Arterial Bed	Completed	NCT01121458	Phase 4	Clevidipine
40	Sildenafil Effects on Pulmonary Haemodynamics and Gas Exchange in Chronic Obstructive Pulmonary Disease (COPD)	Completed	NCT00491803	Phase 4	Sildenafil;Sildenafil
41	REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension	Recruiting	NCT02310672	Phase 4	Macitentan
42	The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study	Recruiting	NCT02253394	Phase 4	Ambrisentan plus Spironolactone;Ambrisentan plus Placebo
43	Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension.	Recruiting	NCT03078907	Phase 4	Selexipag;Placebo
44	To Compare the Efficacy of Combination Therapy vs Monotherapy for Pulmonary Arterial Hypertension in Systemic Sclerosis	Recruiting	NCT03053739	Phase 4	Sildenafil 20mg and Bosentan 62.5mg;Sildenafil 20mg and Placebo
45	Riociguat rEplacing PDE-5i Therapy evaLuated Against Continued PDE-5i thErapy	Recruiting	NCT02891850	Phase 4	Adempas (Riociguat, BAY63-2521);Sildenafil;Tadalafil
46	Crossover Study From Macitentan or Bosentan Over to Ambrisentan	Recruiting	NCT02885012	Phase 4	Ambrisentan
47	A Study to Investigate the Efficacy of PADN to Improved Functional Capacity and Hemodynamics in Patients With PAH	Recruiting	NCT02284737	Phase 4	Sildenafil
48	Effects of Oral Sildenafil on Mortality in Adults With PAH	Recruiting	NCT02060487	Phase 4	sildenafil citrate;sildenafil citrate;sildenafil citrate
49	A Long-term Extension Study of Riociguat in Patients With Symptomatic Pulmonary Arterial Hypertension.	Recruiting	NCT02759419	Phase 4	Adempas (Riociguat, BAY63-2521)
50	Spironolactone Therapy in Chronic Stable Right HF Trial	Recruiting	NCT03344159	Phase 4	Spironolactone;Placebo

Search NIH Clinical Center for Heritable Pulmonary Arterial Hypertension

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Genetic Tests for Heritable Pulmonary Arterial Hypertension

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Anatomical Context for Heritable Pulmonary Arterial Hypertension

MalaCards organs/tissues related to Heritable Pulmonary Arterial Hypertension:

⁴¹

Heart, Lung, Testes, Endothelial, Liver, Bone, Skin

Sources

Publications for Heritable Pulmonary Arterial Hypertension

Articles related to Heritable Pulmonary Arterial Hypertension:

(show all 39)

#	Title	Authors	Year
1	Hypoxemia in patients with idiopathic or heritable pulmonary arterial hypertension. ( 29377954 )	Khirfan G....Tonelli A.R.	2018
2	Identification of rare sequence variation underlying heritable pulmonary arterial hypertension. ( 29650961 )	GrAof S....Morrell N.W.	2018
3	Pulmonary Arterial Capacitance Index Is a Strong Predictor for Adverse Outcome in Children with Idiopathic and Heritable Pulmonary Arterial Hypertension. ( 27810156 )	Takatsuki S....Saji T.	2017
4	Tadalafil in idiopathic or heritable pulmonary arterial hypertension (PAH) compared to PAH associated with connective tissue disease. ( 28279499 )	GaliA" N....Palazzini M.	2017
5	First identification of KrA1ppel-like factor 2 mutation in heritable pulmonary arterial hypertension. ( 28188237 )	Eichstaedt C.A....GrA1nig E.	2017
6	Pulmonary arterial capacitance index is a strong predictor for adverse outcome in children with idiopathic and heritable pulmonary arterial hypertension: methodological issues to avoid misinterpretation. ( 28434572 )	Ayubi E....Safiri S.	2017
7	Hypermethylation of BMPR2 Promoter Occurs in Patients with Heritable Pulmonary Arterial Hypertension and Inhibits BMPR2 Expression. ( 28170297 )	Liu D....Jing Z.C.	2017
8	Survival of Japanese Patients With Idiopathic/Heritable Pulmonary Arterial Hypertension. ( 28267959 )	Ogawa A....Matsubara H.	2017
9	Bilaterally dilated episcleral vessels in patients with heritable pulmonary arterial hypertension. ( 29264093 )	Watanabe M....Obata H.	2017
10	Left main coronary artery compression by a dilated main pulmonary artery and left coronary sinus of Valsalva aneurysm in a patient with heritable pulmonary arterial hypertension and FLNA mutation. ( 28660794 )	Hirashiki A....Kondo T.	2017
11	Clinical Impact of Main Pulmonary Artery Dilatation on Outcome in Pediatric Idiopathic and Heritable Pulmonary Arterial Hypertension. ( 28904266 )	Ikehara S....Saji T.	2017
12	From bone morphogenic protein receptor II mutations to heritable pulmonary arterial hypertension-the long and winding road. ( 27646063 )	Cahill B.C....Ryan J.J.	2016
13	Rapid and high-dose titration of epoprostenol improves pulmonary hemodynamics and clinical outcomes in patients with idiopathic and heritable pulmonary arterial hypertension. ( 27005767 )	Tokunaga N....Matsubara H.	2016
14	Elevated levels of plasma transforming growth factor-I^1 in idiopathic and heritable pulmonary arterial hypertension. ( 27500766 )	Yan Y....Jing Z.C.	2016
15	Serotonin 2B Receptor Antagonism Prevents Heritable Pulmonary Arterial Hypertension. ( 26863209 )	West J.D....Merryman W.D.	2016
16	Pregnancy as a possible trigger for heritable pulmonary arterial hypertension. ( 27683615 )	Limoges M....Lesenko L.	2016
17	De novo mutations in the BMPR2 gene in patients with heritable pulmonary arterial hypertension. ( 25612240 )	Momose Y....Gamou S.	2015
18	MULTIFOCAL CENTRAL SEROUS CHORIORETINOPATHY WITH PHOTORECEPTOR-RETINAL PIGMENT EPITHELIUM DIASTASIS IN HERITABLE PULMONARY ARTERIAL HYPERTENSION. ( 25383848 )	Li X.Q....Larsen M.	2014
19	Identification of a new intronic BMPR2-mutation and early diagnosis of heritable pulmonary arterial hypertension in a large family with mean clinical follow-up of 12 years. ( 24621962 )	Hinderhofer K....GrA1nig E.	2014
20	Non-BMPR2 mutation heritable pulmonary arterial hypertension in Southeast Asia. ( 24948783 )	Pussadhamma B....Barozzi C.	2014
21	Long-term patient survival with idiopathic/heritable pulmonary arterial hypertension treated at a single center in Japan. ( 24530872 )	Ogawa A....Matsubara H.	2014
22	Spleen size in idiopathic and heritable pulmonary arterial hypertension. ( 22869505 )	Tonelli A.R....Dweik R.A.	2013
23	Abnormal trafficking of endogenously expressed BMPR2 mutant allelic products in patients with heritable pulmonary arterial hypertension. ( 24224048 )	Frump A.L....de Caestecker M.	2013
24	Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR2 gene in heritable pulmonary arterial hypertension. ( 23579436 )	Kataoka M....Gamou S.	2013
25	Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR2 gene in heritable pulmonary arterial hypertension. ( 25356964 )		2013
26	Evidence for Right Ventricular Lipotoxicity in Heritable Pulmonary Arterial Hypertension. ( 24274756 )	Hemnes A.R....West J.	2013
27	Role of BMPR2 alternative splicing in heritable pulmonary arterial hypertension penetrance. ( 22923426 )	Cogan J....Hamid R.	2012
28	Heritable pulmonary arterial hypertension with elevated pulmonary wedge pressure. ( 22927477 )	Digne F....Attias D.	2012
29	Molecular genetics and clinical features of Chinese idiopathic and heritable pulmonary arterial hypertension patients. ( 21737554 )	Liu D....Jing Z.C.	2012
30	Impaired natural killer cell phenotype and function in idiopathic and heritable pulmonary arterial hypertension. ( 22832786 )	Ormiston M.L....Morrell N.W.	2012
31	Cardiopulmonary exercise testing reveals onset of disease and response to treatment in a case of heritable pulmonary arterial hypertension. ( 23130108 )	Trip P....Bogaard H.J.	2012
32	Longitudinal analysis casts doubt on the presence of genetic anticipation in heritable pulmonary arterial hypertension. ( 22923661 )	Larkin E.K....Loyd J.E.	2012
33	Prevalence and prognostic value of left ventricular diastolic dysfunction in idiopathic and heritable pulmonary arterial hypertension. ( 22207680 )	Tonelli A.R....Dweik R.A.	2012
34	Unexplained iron deficiency in idiopathic and heritable pulmonary arterial hypertension. ( 21297151 )	Soon E....Pepke-Zaba J.	2011
35	Altered MicroRNA processing in heritable pulmonary arterial hypertension: an important role for Smad-8. ( 21920918 )	Drake K.M....Aldred M.A.	2011
36	Bone morphogenetic protein type II receptor mutations causing protein misfolding in heritable pulmonary arterial hypertension. ( 21030519 )	Li W....Morrell N.W.	2010
37	BMPR2 mutation alters the lung macrophage endothelin-1 cascade in a mouse model and patients with heritable pulmonary artery hypertension. ( 20562228 )	Talati M....Meyrick B.	2010
38	Truncating and missense BMPR2 mutations differentially affect the severity of heritable pulmonary arterial hypertension. ( 19785764 )	Austin E.D....Loyd J.E.	2009
39	Heritable Pulmonary Arterial Hypertension ( 20301658 )	Pagon R.A....Stephens K.	1993

Sources

Genes for Heritable Pulmonary Arterial Hypertension

Genes related to Heritable Pulmonary Arterial Hypertension (8 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence
1	BMPR2	Bone Morphogenetic Protein Receptor Type 2	Protein Coding	368.21	Causative germline mutation (loss of function) ⁵⁹ GeneCards inferred via : Publications (show sections)
2	KCNK3	Potassium Two Pore Domain Channel Subfamily K Member 3	Protein Coding	350	Causative germline mutation (loss of function) ⁵⁹
3	TBX4	T-Box 4	Protein Coding	350	Causative germline mutation ⁵⁹
4	SMAD9	SMAD Family Member 9	Protein Coding	350	Causative germline mutation ⁵⁹
5	EIF2AK4	Eukaryotic Translation Initiation Factor 2 Alpha Kinase 4	Protein Coding	350	Causative germline mutation (loss of function) ⁵⁹
6	CAV1	Caveolin 1	Protein Coding	350	Causative germline mutation ⁵⁹
7	ENG	Endoglin	Protein Coding	25	Candidate gene tested ⁵⁹
8	ACVRL1	Activin A Receptor Like Type 1	Protein Coding	25	Candidate gene tested ⁵⁹
9	TGFB1	Transforming Growth Factor Beta 1	Protein Coding	17.17	GeneCards inferred via : Publications (show sections)
10	KLF2	Kruppel Like Factor 2	Protein Coding	17.17	GeneCards inferred via : Publications (show sections)

Sources

Variations for Heritable Pulmonary Arterial Hypertension

Sources

Expression for Heritable Pulmonary Arterial Hypertension

Search GEO for disease gene expression data for Heritable Pulmonary Arterial Hypertension.

Sources

Pathways for Heritable Pulmonary Arterial Hypertension

Pathways related to Heritable Pulmonary Arterial Hypertension according to GeneCards Suite gene sharing:

(show all 11)

#	Super pathways	Score	Top Affiliating Genes
1	BMP Pathway ⁶⁴ Show member pathways Caspase Cascade ⁶⁴ Depolarization of the Presynaptic Terminal Triggers the Opening of Calcium Channels ⁶⁶ DREAM Repression and Dynorphin Expression ⁶⁴ nNOS Signaling in Skeletal Muscle ⁶⁴ TOB in Osteoblast Signaling ⁶⁴	12.11	ACVRL1 BMPR2 SMAD9
2	Human Embryonic Stem Cell Pluripotency ⁶⁴ Show member pathways Factors Promoting Cardiogenesis in Vertebrates ⁶⁴	12.08	BMPR2 SMAD9 TGFB1
3	Fluid shear stress and atherosclerosis ³⁷	11.72	BMPR2 CAV1 KLF2
4	Wnt / Hedgehog / Notch ⁴	11.72	BMPR2 ENG SMAD9 TGFB1
5	TGF-beta signaling pathway (KEGG) ³⁷	11.42	BMPR2 SMAD9 TGFB1
6	TGF-beta Signaling Pathways ⁶⁵	11.24	ACVRL1 ENG SMAD9 TGFB1
7	TGF-beta receptor signaling (Pathway Interaction Database) ¹	11.2	CAV1 TGFB1
8	TGF-beta Receptor Signaling (WikiPathways) ¹	11.2	ENG SMAD9 TGFB1
9	Cardiomyocyte Differentiation through BMP Receptors ⁶⁴	10.78	BMPR2 SMAD9
10	ALK1 signaling events ¹ Show member pathways ALK1 pathway ¹	10.45	ACVRL1 BMPR2 CAV1 SMAD9 TGFB1
11	ALK2 signaling events ¹	10.41	BMPR2 SMAD9

Sources

GO Terms for Heritable Pulmonary Arterial Hypertension

Cellular components related to Heritable Pulmonary Arterial Hypertension according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	cell surface	GO:0009986	8.92	ACVRL1 BMPR2 ENG TGFB1

Biological processes related to Heritable Pulmonary Arterial Hypertension according to GeneCards Suite gene sharing:

(show all 37)

#	Name	GO ID	Score	Top Affiliating Genes
1	protein phosphorylation	GO:0006468	9.89	ACVRL1 BMPR2 EIF2AK4 SMAD9 TGFB1
2	response to drug	GO:0042493	9.85	ENG KCNK3 TGFB1
3	negative regulation of gene expression	GO:0010629	9.83	ACVRL1 ENG TGFB1
4	response to hypoxia	GO:0001666	9.8	ACVRL1 CAV1 TGFB1
5	negative regulation of cell growth	GO:0030308	9.77	ACVRL1 BMPR2 TGFB1
6	angiogenesis	GO:0001525	9.76	ACVRL1 CAV1 ENG TBX4
7	cellular response to organic cyclic compound	GO:0071407	9.7	KLF2 SMAD9 TGFB1
8	response to progesterone	GO:0032570	9.67	CAV1 TGFB1
9	ureteric bud development	GO:0001657	9.67	SMAD9 TGFB1
10	negative regulation of blood vessel endothelial cell migration	GO:0043537	9.66	ACVRL1 TGFB1
11	negative regulation of endothelial cell proliferation	GO:0001937	9.66	ACVRL1 CAV1
12	positive regulation of bone mineralization	GO:0030501	9.65	BMPR2 TGFB1
13	mammary gland development	GO:0030879	9.65	CAV1 TGFB1
14	vasculogenesis	GO:0001570	9.65	CAV1 ENG TGFB1
15	blood vessel remodeling	GO:0001974	9.64	ACVRL1 BMPR2
16	outflow tract septum morphogenesis	GO:0003148	9.64	BMPR2 ENG
17	positive regulation of collagen biosynthetic process	GO:0032967	9.63	ENG TGFB1
18	regulation of transforming growth factor beta receptor signaling pathway	GO:0017015	9.62	ENG TGFB1
19	transmembrane receptor protein serine/threonine kinase signaling pathway	GO:0007178	9.61	ACVRL1 BMPR2
20	endocardial cushion morphogenesis	GO:0003203	9.61	ACVRL1 ENG
21	cellular response to transforming growth factor beta stimulus	GO:0071560	9.61	ACVRL1 CAV1 TGFB1
22	activin receptor signaling pathway	GO:0032924	9.6	ACVRL1 BMPR2
23	lymphangiogenesis	GO:0001946	9.58	ACVRL1 BMPR2
24	negative regulation of DNA biosynthetic process	GO:2000279	9.58	ACVRL1 BMPR2
25	artery development	GO:0060840	9.57	ACVRL1 BMPR2
26	response to laminar fluid shear stress	GO:0034616	9.56	KLF2 TGFB1
27	dorsal aorta morphogenesis	GO:0035912	9.55	ACVRL1 ENG
28	retina vasculature development in camera-type eye	GO:0061298	9.54	ACVRL1 BMPR2
29	lymphatic endothelial cell differentiation	GO:0060836	9.51	ACVRL1 BMPR2
30	cellular response to BMP stimulus	GO:0071773	9.5	ACVRL1 BMPR2 SMAD9
31	transforming growth factor beta receptor signaling pathway	GO:0007179	9.46	ACVRL1 BMPR2 SMAD9 TGFB1
32	positive regulation of BMP signaling pathway	GO:0030513	9.43	ACVRL1 BMPR2 ENG
33	venous blood vessel development	GO:0060841	9.4	ACVRL1 BMPR2
34	endocardial cushion to mesenchymal transition	GO:0090500	9.37	ACVRL1 ENG
35	positive regulation of pathway-restricted SMAD protein phosphorylation	GO:0010862	9.26	ACVRL1 BMPR2 ENG TGFB1
36	BMP signaling pathway	GO:0030509	9.02	ACVRL1 BMPR2 ENG SMAD9 TGFB1
37	positive regulation of transcription by RNA polymerase II	GO:0045944	10.02	ACVRL1 BMPR2 ENG KLF2 TGFB1

Molecular functions related to Heritable Pulmonary Arterial Hypertension according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	transforming growth factor beta binding	GO:0050431	9.43	ACVRL1 ENG
2	obsolete signal transducer, downstream of receptor, with serine/threonine kinase activity	GO:0004702	9.4	ACVRL1 BMPR2
3	activin binding	GO:0048185	9.37	ACVRL1 ENG
4	transmembrane receptor protein serine/threonine kinase activity	GO:0004675	9.32	ACVRL1 BMPR2
5	type I transforming growth factor beta receptor binding	GO:0034713	9.26	ENG TGFB1
6	BMP binding	GO:0036122	9.16	BMPR2 ENG
7	type II transforming growth factor beta receptor binding	GO:0005114	8.96	ENG TGFB1
8	BMP receptor activity	GO:0098821	8.62	ACVRL1 BMPR2

Sources

Sources for Heritable Pulmonary Arterial Hypertension

¹ BioSystems

² BitterDB

³ CDC

⁴ Cell Signaling Technology

⁵ ClinicalTrials

⁶ ClinVar

⁷ CNVD

⁸ Cochrane Library

⁹ Cosmic

¹⁰ dbSNP

¹¹ DGIdb

¹² Disease Ontology

¹³ diseasecard

¹⁴ DiseaseEnhancer

¹⁵ DISEASES

¹⁶ DrugBank

¹⁷ ExPASy

¹⁸ FDA Approved Drugs

¹⁹ FMA

²⁰ GeneAnalytics

²¹ GeneCards

²² GeneGo (Thomson Reuters)

²³ GeneHancer via GeneCards

²⁴ GeneReviews

²⁵ Genetics Home Reference

²⁶ GenomeRNAi

²⁷ GEO DataSets

²⁸ GO

²⁹ GTR

³⁰ HGMD

³¹ HMDB

³² HPO

³³ ICD10

³⁴ ICD10 via Orphanet

³⁵ ICD9CM

³⁶ IUPHAR

³⁷ KEGG

³⁸ LifeMap

³⁹ LncRNADisease

⁴⁰ LOVD

⁴¹ MalaCards

⁴² MedGen

⁴³ MedlinePlus

⁴⁴ MeSH

⁴⁵ MESH via Orphanet

⁴⁶ MGI

⁴⁷ miR2Disease

⁴⁸ NCBI Bookshelf

⁴⁹ NCI

⁵⁰ NCIt

⁵¹ NDF-RT

⁵² NIH Clinical Center

⁵³ NIH Rare Diseases

⁵⁴ NINDS

⁵⁵ Novoseek

⁵⁶ Novus Biologicals

⁵⁷ OMIM

⁵⁸ OMIM via Orphanet

⁵⁹ Orphanet

⁶⁰ PathCards

⁶¹ PharmGKB

⁶² PubMed

⁶³ PubMed Health

⁶⁴ QIAGEN

⁶⁵ R&D Systems

⁶⁶ Reactome

⁶⁷ Sino Biological

⁶⁸ SNOMED-CT

⁶⁹ SNOMED-CT via HPO

⁷⁰ SNOMED-CT via Orphanet

⁷¹ TGDB

⁷² Tocris

⁷³ UMLS

⁷⁴ UMLS via Orphanet

⁷⁵ UniProtKB/Swiss-Prot

⁷⁶ Wikipedia