PPH4
MCID: PLM121
MIFTS: 28

Pulmonary Hypertension, Primary, 4 (PPH4)

Categories: Blood diseases, Cardiovascular diseases, Genetic diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Pulmonary Hypertension, Primary, 4

MalaCards integrated aliases for Pulmonary Hypertension, Primary, 4:

Name: Pulmonary Hypertension, Primary, 4 56 73 71
Primary Pulmonary Hypertension 4 29 6
Pph4 56 73
Hypertension, Pulmonary, Primary, Type 4 39

Characteristics:

OMIM:

56
Miscellaneous:
incomplete penetrance
progressive disorder
variable age at onset (childhood to adulthood)

Inheritance:
autosomal dominant


HPO:

31
pulmonary hypertension, primary, 4:
Inheritance autosomal dominant inheritance
Onset and clinical course progressive incomplete penetrance


Classifications:



External Ids:

OMIM 56 615344
OMIM Phenotypic Series 56 PS178600
MeSH 43 D006976
UMLS 71 C3809198

Summaries for Pulmonary Hypertension, Primary, 4

OMIM : 56 Primary pulmonary hypertension is a rare progressive disease characterized by increased pulmonary artery pressure in the absence of common causes of pulmonary hypertension, such as chronic heart, lung, or thromboembolic disease. There is often vascular remodeling. The clinical presentation can be nonspecific, and patients often receive a diagnosis late in their clinical course (summary by Ma et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of primary pulmonary hypertension, see PPH1 (178600). (615344)

MalaCards based summary : Pulmonary Hypertension, Primary, 4, is also known as primary pulmonary hypertension 4. An important gene associated with Pulmonary Hypertension, Primary, 4 is KCNK3 (Potassium Two Pore Domain Channel Subfamily K Member 3). Affiliated tissues include heart, lung and endothelial, and related phenotypes are arrhythmia and pulmonary arterial hypertension

UniProtKB/Swiss-Prot : 73 Pulmonary hypertension, primary, 4: A rare disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs.

Related Diseases for Pulmonary Hypertension, Primary, 4

Symptoms & Phenotypes for Pulmonary Hypertension, Primary, 4

Human phenotypes related to Pulmonary Hypertension, Primary, 4:

31
# Description HPO Frequency HPO Source Accession
1 arrhythmia 31 occasional (7.5%) HP:0011675
2 pulmonary arterial hypertension 31 HP:0002092
3 increased pulmonary vascular resistance 31 HP:0005317

Symptoms via clinical synopsis from OMIM:

56
Cardiovascular Vascular:
increased pulmonary vascular resistance
plexiform vascular lesions
increased pulmonary artery pressure
pulmonary arteries show medial hypertrophy
pulmonary arterial vascular wall remodeling
more
Cardiovascular Heart:
cardiac arrhythmias (in some patients)

Clinical features from OMIM:

615344

Drugs & Therapeutics for Pulmonary Hypertension, Primary, 4

Search Clinical Trials , NIH Clinical Center for Pulmonary Hypertension, Primary, 4

Genetic Tests for Pulmonary Hypertension, Primary, 4

Genetic tests related to Pulmonary Hypertension, Primary, 4:

# Genetic test Affiliating Genes
1 Primary Pulmonary Hypertension 4 29 KCNK3

Anatomical Context for Pulmonary Hypertension, Primary, 4

MalaCards organs/tissues related to Pulmonary Hypertension, Primary, 4:

40
Heart, Lung, Endothelial

Publications for Pulmonary Hypertension, Primary, 4

Articles related to Pulmonary Hypertension, Primary, 4:

(show top 50) (show all 103)
# Title Authors PMID Year
1
A novel channelopathy in pulmonary arterial hypertension. 56 6
23883380 2013
2
Heritable Pulmonary Arterial Hypertension 6
20301658 2002
3
The First Organosilver(III) Fluoride, [PPh4 ][(CF3 )3 AgF]. 61
31881098 2020
4
Polymorphic Copper Iodide Anions: Luminescence Thermochromism and Mechanochromism of (PPh4)2[Cu2I4]. 61
32233459 2020
5
Field-induced slow magnetic relaxation in low-spin S = 1/2 mononuclear osmium(v) complexes. 61
32134093 2020
6
Origin of ferromagnetism and magnetic anisotropy in a family of copper(II) triangles. 61
32343007 2020
7
Heterometallic 3d-4d coordination polymers assembled from trans-[RuIII(L)(CN)2]- tectons and 3d cations. 61
31204750 2019
8
Homogeneously-catalysed hydrogen release/storage using the 2-methylindole/2-methylindoline LOHC system in molten salt-organic biphasic reaction systems. 61
30687857 2019
9
Synthesis and structural characterisation of unprecedented primary N-nitrosamines coordinated to iridium(iv). 61
30065990 2018
10
The Binary Group 4 Azides [PPh4 ]2 [Zr(N3 )6 ] and [PPh4 ]2 [Hf(N3 )6 ]. 61
27735115 2016
11
The niobium oxoazides [NbO(N3)3], [NbO(N3)3·2CH3CN], [(bipy)NbO(N3)3], Cs2[NbO(N3)5] and [PPh4]2[NbO(N3)5]. 61
27198621 2016
12
Polarized Neutron Diffraction to Probe Local Magnetic Anisotropy of a Low-Spin Fe(III) Complex. 61
26890339 2016
13
Reactivity of a Fe(III)-Bound Methoxide Supported with a Tris(thiolato)phosphine Ligand: Activation of C-Cl Bond in CH2Cl2 by Nucleophilic Attack of a Fe(III)-OCH3 Moiety. 61
26699874 2016
14
Silicon- and Tin-Containing Open-Chain and Eight-Membered-Ring Compounds as Bicentric Lewis Acids toward Anions. 61
26616743 2016
15
The Molybdenum(V) and Tungsten(VI) Oxoazides [MoO(N3 )3 ], [MoO(N3 )3 ⋅2 CH3 CN], [(bipy)MoO(N3 )3 ], [MoO(N3 )5 ](2-) , [WO(N3 )4 ], and [WO(N3 )4 ⋅CH3 CN]. 61
26768534 2015
16
Magneto-Structural Correlations in a Series of Pseudotetrahedral [Co(II)(XR)4](2-) Single Molecule Magnets: An ab Initio Ligand Field Study. 61
26443918 2015
17
The First Molybdenum(VI) and Tungsten(VI) Oxoazides MO2(N3)2, MO2(N3)2⋅2 CH3CN, (bipy)MO2(N3)2, and [MO2(N3)4](2-) (M=Mo, W). 61
26178877 2015
18
The Vanadium(V) Oxoazides [VO(N3)3], [(bipy)VO(N3)3], and [VO(N3)5](2-). 61
26072899 2015
19
Non-oxido divanadium(IV) and divanadium(V) thiolate complexes with a new type of chalcogenide bridging motif. 61
25645817 2015
20
Synthesis, crystal structures and magnetic properties of mer-cyanideiron(III)-based 1D heterobimetallic cyanide-bridged chiral coordination polymers. 61
25661782 2015
21
Synthesis and structural characterization of 3,5-dinitro-1,2,4-triazolates. 61
25615958 2015
22
Water-induced formation, characterization, and photoluminescence of carbon nanotube-based composites of gadolinium(III) and platinum(II) dithiolenes. 61
25331915 2014
23
Synthesis of functional phosphates [P(C2F5)3F2X]- from the phosphorane adduct [P(C2F5)3F2(dmap)]. 61
24986082 2014
24
Preparation of the first manganese(III) and manganese(IV) azides. 61
25044947 2014
25
Sulfur K-edge X-ray absorption spectroscopy and time-dependent density functional theory of arsenic dithiocarbamates. 61
24811926 2014
26
Highly efficient alkane oxidation catalyzed by [Mn(V)(N)(CN)4](2-). Evidence for [Mn(VII)(N)(O)(CN)4](2-) as an active intermediate. 61
24799179 2014
27
Gallium phosphinoarylbisthiolato complexes counteract drug resistance of cancer cells. 61
24413432 2014
28
Synthesis, structure and cation-binding properties of some [4 + 4] metallocyclic MO2(2+) (M = Mo or W) derivatives of 9-phenyl-2,3,7-trihydroxyfluor-6-one. 61
24484205 2014
29
Synthesis of five- and six-coordinate tris(pentafluoroethyl)fluorosilicates. 61
24288152 2014
30
[ReF(6)](2-) : a robust module for the design of molecule-based magnetic materials. 61
24459056 2014
31
Gold(I) and gold(III) trifluoromethyl derivatives. 61
24027236 2013
32
Exploring the interplay between ligand derivatisation and cation type in the assembly of hybrid polyoxometalate Mn-Andersons. 61
23401298 2013
33
Excited-state characteristics of tetracyanidonitridorhenium(V) and -technetium(V) complexes with N-heteroaromatic ligands. 61
23679193 2013
34
Energetic bis(3,5-dinitro-1H-1,2,4-triazolyl)dihydro- and dichloroborates and bis(5-nitro-2H-tetrazolyl)-, bis(5-(trinitromethyl)-2H-tetrazolyl)-, and bis(5-(fluorodinitromethyl)-2H-tetrazolyl)dihydroborate. 61
23614398 2013
35
Unprecedented conformational variability in main group inorganic chemistry: the tetraazidoarsenite and -antimonite salts A+ [M(N3)4]- (A = NMe4, PPh4, (Ph3P)2N; M = As, Sb), five similar salts, five different anion structures. 61
23214472 2013
36
Photoluminescence switching with changes in the coordination number and coordinating volatile organic compounds in tetracyanidonitridorhenium(V) and -technetium(V) complexes. 61
23121620 2012
37
[Blood pressure changes in chronically haemodialysed patients]. 61
22486283 2012
38
Syntheses and crystal structures of the closo-borate M[B8H9] (M = [PPh4]+ and [N(n-Bu4)]+). 61
22136316 2012
39
Thermal stability, optical property, and morphology of flexible organoclay films. 61
22121657 2011
40
Dangling thiyl radical: stabilized in [PPh4]2[(bdt)W(VI)(O)(μ-S)2Cu(I)(SC6H4S•)]. 61
21452808 2011
41
Syntheses and crystal structures of the closo-borates M2[B7H7] and M[B7H8] (M = PPh4, PNP, and N(n-Bu4)): the missing crystal structure in the series [B(n)H(n)]2- (n = 6-12). 61
21341737 2011
42
Efficient olefin epoxidation by robust Re4 cluster-supported Mn(III) complexes with peracids: evidence of simultaneous operation of multiple active oxidant species, Mn(V)=O, Mn(IV)=O, and Mn(III)-OOC(O)R. 61
20235245 2010
43
Organic-soluble optically pure anionic metal complexes PPh4[M(III)(S,S-EDDS)].2H2O (M = Fe, Co, Cr). 61
20200720 2010
44
Ferromagnetic coupled mu-phenoxo-mu-carboxylato heterodinuclear complexes based on the Cr(salen) moiety: structural and magnetic characterization. 61
19759938 2009
45
Synthesis and reactivity of metal carbene complexes with heterobiaryl spacer substituents. 61
19378563 2009
46
Controlled super-structures of hydrogen bonding Ni(II) complexes organizing one-dimensional double cationic arrays. 61
19441311 2009
47
Nano-film structures constructed by self-assembly of Co(III) biuretato complexes and long alkyl imidazolium cations. 61
19441312 2009
48
Molecular and electronic structure of the square planar bis(o-amidobenzenethiolato)iron(III) anion and its bis(o-quinoxalinedithiolato)iron(III) analogue. 61
18989920 2008
49
Assembly of [(eta5-C5Me5)MoS3Cu3]-supported one-dimensional chains with single, double, triple, and quadruple strands. 61
18484718 2008
50
Structural chemistry of (PPh4)2M(WS4)2 materials. 61
18335143 2008

Variations for Pulmonary Hypertension, Primary, 4

ClinVar genetic disease variations for Pulmonary Hypertension, Primary, 4:

6 (show all 35) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 KCNK3 NM_002246.3(KCNK3):c.23C>A (p.Thr8Lys)SNV Pathogenic 426049 rs1085307438 2:26915766-26915766 2:26692898-26692898
2 KCNK3 NM_002246.3(KCNK3):c.608G>A (p.Gly203Asp)SNV Pathogenic 60479 rs398123039 2:26950859-26950859 2:26727991-26727991
3 KCNK3 NM_002246.3(KCNK3):c.289G>A (p.Gly97Arg)SNV Pathogenic 60480 rs398123040 2:26950540-26950540 2:26727672-26727672
4 KCNK3 NM_002246.3(KCNK3):c.661G>C (p.Val221Leu)SNV Pathogenic 60481 rs398123041 2:26950912-26950912 2:26728044-26728044
5 KCNK3 NM_002246.3(KCNK3):c.544G>A (p.Glu182Lys)SNV Pathogenic 60482 rs398123042 2:26950795-26950795 2:26727927-26727927
6 KCNK3 NM_002246.3(KCNK3):c.575A>G (p.Tyr192Cys)SNV Pathogenic 60483 rs398123043 2:26950826-26950826 2:26727958-26727958
7 KCNK3 NM_002246.3(KCNK3):c.365T>C (p.Leu122Pro)SNV Likely pathogenic 548009 rs1553387422 2:26950616-26950616 2:26727748-26727748
8 KCNK3 NM_002246.3(KCNK3):c.834C>A (p.Ser278Arg)SNV Uncertain significance 580390 rs750738078 2:26951085-26951085 2:26728217-26728217
9 KCNK3 NM_002246.3(KCNK3):c.275C>T (p.Thr92Ile)SNV Uncertain significance 811790 2:26916018-26916018 2:26693150-26693150
10 KCNK3 NM_002246.3(KCNK3):c.967T>A (p.Tyr323Asn)SNV Uncertain significance 862866 2:26951218-26951218 2:26728350-26728350
11 KCNK3 NM_002246.3(KCNK3):c.1067C>A (p.Thr356Lys)SNV Uncertain significance 864183 2:26951318-26951318 2:26728450-26728450
12 KCNK3 NM_002246.3(KCNK3):c.17T>C (p.Val6Ala)SNV Uncertain significance 474319 rs1226314697 2:26915760-26915760 2:26692892-26692892
13 KCNK3 NM_002246.3(KCNK3):c.172G>A (p.Gly58Ser)SNV Uncertain significance 474318 rs753384871 2:26915915-26915915 2:26693047-26693047
14 KCNK3 NM_002246.3(KCNK3):c.1180G>A (p.Val394Met)SNV Uncertain significance 474317 rs1553387738 2:26951431-26951431 2:26728563-26728563
15 KCNK3 NM_002246.3(KCNK3):c.100G>A (p.Glu34Lys)SNV Uncertain significance 474316 rs1553383771 2:26915843-26915843 2:26692975-26692975
16 KCNK3 NM_002246.3(KCNK3):c.832A>T (p.Ser278Cys)SNV Uncertain significance 541325 rs368524386 2:26951083-26951083 2:26728215-26728215
17 KCNK3 NM_002246.3(KCNK3):c.547C>T (p.His183Tyr)SNV Uncertain significance 578932 rs1558604738 2:26950798-26950798 2:26727930-26727930
18 KCNK3 NM_002246.3(KCNK3):c.646_651dup (p.Thr216_Gln217dup)duplication Uncertain significance 580894 rs1558604795 2:26950892-26950893 2:26728024-26728025
19 KCNK3 NM_002246.3(KCNK3):c.844A>G (p.Thr282Ala)SNV Uncertain significance 575685 rs779537390 2:26951095-26951095 2:26728227-26728227
20 KCNK3 NM_002246.3(KCNK3):c.1169G>A (p.Arg390His)SNV Uncertain significance 576185 rs868278570 2:26951420-26951420 2:26728552-26728552
21 KCNK3 NM_002246.3(KCNK3):c.250_267dup (p.Phe84_Thr89dup)duplication Uncertain significance 592111 rs1558592501 2:26915990-26915991 2:26693122-26693123
22 KCNK3 NM_002246.3(KCNK3):c.618G>A (p.Val206=)SNV Uncertain significance 648112 2:26950869-26950869 2:26728001-26728001
23 KCNK3 NM_002246.3(KCNK3):c.785C>T (p.Ala262Val)SNV Uncertain significance 653289 2:26951036-26951036 2:26728168-26728168
24 KCNK3 NM_002246.3(KCNK3):c.903G>A (p.Ala301=)SNV Uncertain significance 654608 2:26951154-26951154 2:26728286-26728286
25 KCNK3 NM_002246.3(KCNK3):c.1128G>A (p.Thr376=)SNV Uncertain significance 645379 2:26951379-26951379 2:26728511-26728511
26 KCNK3 NM_002246.3(KCNK3):c.283+6G>TSNV Uncertain significance 658020 2:26916032-26916032 2:26693164-26693164
27 KCNK3 NM_002246.3(KCNK3):c.1140C>G (p.Ser380Arg)SNV Likely benign 704801 2:26951391-26951391 2:26728523-26728523
28 KCNK3 NM_002246.3(KCNK3):c.456C>T (p.Ala152=)SNV Likely benign 704086 2:26950707-26950707 2:26727839-26727839
29 KCNK3 NM_002246.3(KCNK3):c.120G>A (p.Arg40=)SNV Likely benign 794692 2:26915863-26915863 2:26692995-26692995
30 KCNK3 NM_002246.3(KCNK3):c.1014G>A (p.Thr338=)SNV Likely benign 541326 rs375930383 2:26951265-26951265 2:26728397-26728397
31 KCNK3 NM_002246.3(KCNK3):c.423C>A (p.His141Gln)SNV Likely benign 474321 rs151228365 2:26950674-26950674 2:26727806-26727806
32 KCNK3 NM_002246.3(KCNK3):c.366C>T (p.Leu122=)SNV Likely benign 474320 rs61736657 2:26950617-26950617 2:26727749-26727749
33 KCNK3 NM_002246.3(KCNK3):c.1097C>T (p.Ala366Val)SNV Likely benign 811685 2:26951348-26951348 2:26728480-26728480
34 KCNK3 NM_002246.3(KCNK3):c.953G>A (p.Arg318His)SNV Benign 569441 rs150626749 2:26951204-26951204 2:26728336-26728336
35 KCNK3 NM_002246.3(KCNK3):c.654G>T (p.Pro218=)SNV Benign 474322 rs34292597 2:26950905-26950905 2:26728037-26728037

UniProtKB/Swiss-Prot genetic disease variations for Pulmonary Hypertension, Primary, 4:

73
# Symbol AA change Variation ID SNP ID
1 KCNK3 p.Thr8Lys VAR_070126 rs108530743
2 KCNK3 p.Gly97Arg VAR_070127 rs398123040
3 KCNK3 p.Glu182Lys VAR_070128 rs398123042
4 KCNK3 p.Tyr192Cys VAR_070129 rs398123043
5 KCNK3 p.Gly203Asp VAR_070130 rs398123039
6 KCNK3 p.Val221Leu VAR_070131 rs398123041

Expression for Pulmonary Hypertension, Primary, 4

Search GEO for disease gene expression data for Pulmonary Hypertension, Primary, 4.

Pathways for Pulmonary Hypertension, Primary, 4

GO Terms for Pulmonary Hypertension, Primary, 4

Sources for Pulmonary Hypertension, Primary, 4

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