Details of Disease

General Information of Disease (ID: DISD1Y94)

• Disease Name: Heritable pulmonary arterial hypertension
• Synonyms: HpaH; familial pulmonary arterial hypertension; FPAH; hereditary pulmonary arterial hypertension
• Definition: Heritable pulmonary arterial hypertension (HPAH) is a form of pulmonary arterial hypertension (PAH), occurring due to mutations in PAH predisposing genes or in a familial context. HPAH is characterized by elevated pulmonary arterial resistance leading to right heart failure. HPAH is progressive and potentially fatal.
• Disease Hierarchy:
  DISYKSRF: Genetic disease
  DISP8ZX5: Pulmonary arterial hypertension
  DISD1Y94: Heritable pulmonary arterial hypertension
• Disease Identifiers:
  MONDO ID: MONDO_0017148
  MESH ID: D065627
  UMLS CUI: C0340543
  MedGen ID: 90953
  Orphanet ID: 275777
  SNOMED CT ID: 233944003

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 19 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
PAH	TTGSVH2	Limited	Genetic Variation	[1]
BMPR2	TTGKF90	Supportive	Autosomal dominant	[2]
CAV1	TTXUBN2	Supportive	Autosomal dominant	[3]
EIF2AK4	TT9U4EP	Supportive	Autosomal dominant	[4]
KCNK3	TTGR91N	Supportive	Autosomal dominant	[5]
SMAD9	TTX8EBV	Supportive	Autosomal dominant	[6]
AQP1	TTSF1KH	moderate	Biomarker	[7]
BMPR2	TTGKF90	moderate	Genetic Variation	[8]
CAV1	TTXUBN2	moderate	Biomarker	[7]
SMAD1	TT9GR53	moderate	Biomarker	[7]
ACVRL1	TTGYPTC	Strong	Genetic Variation	[9]
EIF2AK4	TT9U4EP	Strong	Biomarker	[10]
ENG	TTB30LE	Strong	Genetic Variation	[11]
GDF2	TTAP4T1	Strong	Biomarker	[12]
HDAC1	TT6R7JZ	Strong	Biomarker	[13]
HDAC4	TTTQGH8	Strong	Biomarker	[13]
HDAC5	TTUELN5	Strong	Biomarker	[13]
KCNK3	TTGR91N	Strong	Biomarker	[14]
SMAD9	TTX8EBV	Strong	Biomarker	[15]

This Disease Is Related to 12 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
BMPR2	OTM9W547	Supportive	Autosomal dominant	[2]
CAV1	OTEZUR1L	Supportive	Autosomal dominant	[3]
EIF2AK4	OTLE1JY8	Supportive	Autosomal dominant	[4]
KCNK3	OTWMAV6G	Supportive	Autosomal dominant	[5]
SMAD9	OTK4M1H8	Supportive	Autosomal dominant	[6]
TBX4	OTW58FG4	Supportive	Autosomal dominant	[16]
SMAD4	OTWQWCKG	moderate	Biomarker	[7]
ATP13A3	OT5EGV3F	Strong	Biomarker	[17]
HBG2	OT4J48JJ	Strong	Biomarker	[18]
PLA1A	OT2IXYNX	Strong	Altered Expression	[19]
PRM3	OT6574BF	Strong	Genetic Variation	[11]
SOX17	OT9H4WWE	Strong	Biomarker	[20]

References

• [1] First identification of Krppel-like factor 2 mutation in heritable pulmonary arterial hypertension.Clin Sci (Lond). 2017 Apr 25;131(8):689-698. doi: 10.1042/CS20160930. Epub 2017 Feb 10.
• [2] Genetics and genomics of pulmonary arterial hypertension. J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S32-S42. doi: 10.1016/j.jacc.2009.04.015.
• [3] Whole exome sequencing to identify a novel gene (caveolin-1) associated with human pulmonary arterial hypertension. Circ Cardiovasc Genet. 2012 Jun;5(3):336-43. doi: 10.1161/CIRCGENETICS.111.961888. Epub 2012 Apr 2.
• [4] A founder EIF2AK4 mutation causes an aggressive form of pulmonary arterial hypertension in Iberian Gypsies. Clin Genet. 2015 Dec;88(6):579-83. doi: 10.1111/cge.12549. Epub 2015 Jan 7.
• [5] A novel channelopathy in pulmonary arterial hypertension. N Engl J Med. 2013 Jul 25;369(4):351-361. doi: 10.1056/NEJMoa1211097.
• [6] Altered MicroRNA processing in heritable pulmonary arterial hypertension: an important role for Smad-8. Am J Respir Crit Care Med. 2011 Dec 15;184(12):1400-8. doi: 10.1164/rccm.201106-1130OC. Epub 2011 Sep 15.
• [7] Identification of rare sequence variation underlying heritable pulmonary arterial hypertension.Nat Commun. 2018 Apr 12;9(1):1416. doi: 10.1038/s41467-018-03672-4.
• [8] Genetic linkage analysis of a large family identifies FIGN as a candidate modulator of reduced penetrance in heritable pulmonary arterial hypertension.J Med Genet. 2019 Jul;56(7):481-490. doi: 10.1136/jmedgenet-2018-105669. Epub 2019 Mar 20.
• [9] Pulmonary Hypertension in a Large Cohort with Hereditary Hemorrhagic Telangiectasia.Respiration. 2017;94(3):242-250. doi: 10.1159/000458447. Epub 2017 Jul 26.
• [10] Response by Hadinnapola et al to Letter Regarding Article, "Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension".Circulation. 2018 May 29;137(22):2413-2414. doi: 10.1161/CIRCULATIONAHA.118.033970.
• [11] Genetics of pulmonary hypertension in the clinic.Curr Opin Pulm Med. 2017 Sep;23(5):386-391. doi: 10.1097/MCP.0000000000000414.
• [12] Novel homozygous BMP9 nonsense mutation causes pulmonary arterial hypertension: a case report.BMC Pulm Med. 2016 Jan 22;16:17. doi: 10.1186/s12890-016-0183-7.
• [13] Histone deacetylation inhibition in pulmonary hypertension: therapeutic potential of valproic acid and suberoylanilide hydroxamic acid.Circulation. 2012 Jul 24;126(4):455-67. doi: 10.1161/CIRCULATIONAHA.112.103176. Epub 2012 Jun 18.
• [14] Characterization and regulation of wild-type and mutant TASK-1 two pore domain potassium channels indicated in pulmonary arterial hypertension. J Physiol. 2019 Feb;597(4):1087-1101. doi: 10.1113/JP277275. Epub 2018 Nov 24.
• [15] Pulmonary Arterial Hypertension: A Current Perspective on Established and Emerging Molecular Genetic Defects.Hum Mutat. 2015 Dec;36(12):1113-27. doi: 10.1002/humu.22904. Epub 2015 Oct 12.
• [16] Genome-wide association analysis identifies a susceptibility locus for pulmonary arterial hypertension. Nat Genet. 2013 May;45(5):518-21. doi: 10.1038/ng.2581. Epub 2013 Mar 17.
• [17] Genetics and genomics of pulmonary arterial hypertension.Eur Respir J. 2019 Jan 24;53(1):1801899. doi: 10.1183/13993003.01899-2018. Print 2019 Jan.
• [18] Familial association of primary pulmonary hypertension and a new low-oxygen affinity beta-chain hemoglobinopathy, Hb Washtenaw.Chest. 1996 Mar;109(3):848-50. doi: 10.1378/chest.109.3.848.
• [19] Abnormal trafficking of endogenously expressed BMPR2 mutant allelic products in patients with heritable pulmonary arterial hypertension.PLoS One. 2013 Nov 5;8(11):e80319. doi: 10.1371/journal.pone.0080319. eCollection 2013.
• [20] SOX17 Mutations in Japanese Patients with Pulmonary Arterial Hypertension.Am J Respir Crit Care Med. 2018 Nov 1;198(9):1231-1233. doi: 10.1164/rccm.201804-0766LE.