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 57 72 70
Primary Pulmonary Hypertension 4 29 6
Pph4 57 72
Hypertension, Pulmonary, Primary, Type 4 39

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
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® 57 615344
OMIM Phenotypic Series 57 PS178600
MeSH 44 D006976
UMLS 70 C3809198

Summaries for Pulmonary Hypertension, Primary, 4

OMIM® : 57 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) (Updated 20-May-2021)

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 endothelial, and related phenotypes are arrhythmia and pulmonary arterial hypertension

UniProtKB/Swiss-Prot : 72 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®:

57 (Updated 20-May-2021)
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 (Updated 20-May-2021)

Drugs & Therapeutics for Pulmonary Hypertension, Primary, 4

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Role of Inflammation and Angiogenesis in Chronic Thromboembolic Pulmonary Hypertension Completed NCT04472533

Search 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
Endothelial

Publications for Pulmonary Hypertension, Primary, 4

Articles related to Pulmonary Hypertension, Primary, 4:

(show top 50) (show all 104)
# Title Authors PMID Year
1
A novel channelopathy in pulmonary arterial hypertension. 6 57
23883380 2013
2
Cl@Ag22 Au6 (4-TBBT)28 (PPh4 ): A Chloride-Centered Ag-Au Bimetallic Cluster for Optics. 61
33047476 2020
3
Trapping of Brønsted acids with a phosphorus-centered biradicaloid - synthesis of hydrogen pseudohalide addition products. 61
32985638 2020
4
Cyanide-Bridged Polynuclear and One-Dimensional FeIII-MnIII/II Bimetallic Complexes Based-on Pentacyanoferrite(III) Building Block: Synthesis, Crystal Structures, and Magnetic Properties. 61
33533419 2020
5
[Cu32(PET)24H8Cl2](PPh4)2: A Copper Hydride Nanocluster with a Bisquare Antiprismatic Core. 61
32672452 2020
6
Polymorphic Copper Iodide Anions: Luminescence Thermochromism and Mechanochromism of (PPh4)2[Cu2I4]. 61
32233459 2020
7
The First Organosilver(III) Fluoride, [PPh4 ][(CF3 )3 AgF]. 61
31881098 2020
8
Field-induced slow magnetic relaxation in low-spin S = 1/2 mononuclear osmium(v) complexes. 61
32134093 2020
9
Heterometallic 3d-4d coordination polymers assembled from trans-[RuIII(L)(CN)2]- tectons and 3d cations. 61
31204750 2019
10
Homogeneously-catalysed hydrogen release/storage using the 2-methylindole/2-methylindoline LOHC system in molten salt-organic biphasic reaction systems. 61
30687857 2019
11
Synthesis and structural characterisation of unprecedented primary N-nitrosamines coordinated to iridium(iv). 61
30065990 2018
12
The Binary Group 4 Azides [PPh4 ]2 [Zr(N3 )6 ] and [PPh4 ]2 [Hf(N3 )6 ]. 61
27735115 2016
13
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
14
Polarized Neutron Diffraction to Probe Local Magnetic Anisotropy of a Low-Spin Fe(III) Complex. 61
26890339 2016
15
Silicon- and Tin-Containing Open-Chain and Eight-Membered-Ring Compounds as Bicentric Lewis Acids toward Anions. 61
26616743 2016
16
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
17
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
18
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
19
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
20
The Vanadium(V) Oxoazides [VO(N3)3], [(bipy)VO(N3)3], and [VO(N3)5](2-). 61
26072899 2015
21
Non-oxido divanadium(IV) and divanadium(V) thiolate complexes with a new type of chalcogenide bridging motif. 61
25645817 2015
22
Synthesis, crystal structures and magnetic properties of mer-cyanideiron(III)-based 1D heterobimetallic cyanide-bridged chiral coordination polymers. 61
25661782 2015
23
Synthesis and structural characterization of 3,5-dinitro-1,2,4-triazolates. 61
25615958 2015
24
Water-induced formation, characterization, and photoluminescence of carbon nanotube-based composites of gadolinium(III) and platinum(II) dithiolenes. 61
25331915 2014
25
Synthesis of functional phosphates [P(C2F5)3F2X]- from the phosphorane adduct [P(C2F5)3F2(dmap)]. 61
24986082 2014
26
Preparation of the first manganese(III) and manganese(IV) azides. 61
25044947 2014
27
Sulfur K-edge X-ray absorption spectroscopy and time-dependent density functional theory of arsenic dithiocarbamates. 61
24811926 2014
28
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
29
Gallium phosphinoarylbisthiolato complexes counteract drug resistance of cancer cells. 61
24413432 2014
30
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
31
Synthesis of five- and six-coordinate tris(pentafluoroethyl)fluorosilicates. 61
24288152 2014
32
[ReF(6)](2-) : a robust module for the design of molecule-based magnetic materials. 61
24459056 2014
33
Gold(I) and gold(III) trifluoromethyl derivatives. 61
24027236 2013
34
Exploring the interplay between ligand derivatisation and cation type in the assembly of hybrid polyoxometalate Mn-Andersons. 61
23401298 2013
35
Excited-state characteristics of tetracyanidonitridorhenium(V) and -technetium(V) complexes with N-heteroaromatic ligands. 61
23679193 2013
36
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
37
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
38
Photoluminescence switching with changes in the coordination number and coordinating volatile organic compounds in tetracyanidonitridorhenium(V) and -technetium(V) complexes. 61
23121620 2012
39
[Blood pressure changes in chronically haemodialysed patients]. 61
22486283 2012
40
Syntheses and crystal structures of the closo-borate M[B8H9] (M = [PPh4]+ and [N(n-Bu4)]+). 61
22136316 2012
41
Thermal stability, optical property, and morphology of flexible organoclay films. 61
22121657 2011
42
Dangling thiyl radical: stabilized in [PPh4]2[(bdt)W(VI)(O)(μ-S)2Cu(I)(SC6H4S•)]. 61
21452808 2011
43
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
44
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
45
Organic-soluble optically pure anionic metal complexes PPh4[M(III)(S,S-EDDS)].2H2O (M = Fe, Co, Cr). 61
20200720 2010
46
Ferromagnetic coupled mu-phenoxo-mu-carboxylato heterodinuclear complexes based on the Cr(salen) moiety: structural and magnetic characterization. 61
19759938 2009
47
Synthesis and reactivity of metal carbene complexes with heterobiaryl spacer substituents. 61
19378563 2009
48
Controlled super-structures of hydrogen bonding Ni(II) complexes organizing one-dimensional double cationic arrays. 61
19441311 2009
49
Nano-film structures constructed by self-assembly of Co(III) biuretato complexes and long alkyl imidazolium cations. 61
19441312 2009
50
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

Variations for Pulmonary Hypertension, Primary, 4

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

6 (show all 47)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 KCNK3 NM_002246.3(KCNK3):c.289G>A (p.Gly97Arg) SNV Pathogenic 60480 rs398123040 GRCh37: 2:26950540-26950540
GRCh38: 2:26727672-26727672
2 KCNK3 NM_002246.3(KCNK3):c.661G>C (p.Val221Leu) SNV Pathogenic 60481 rs398123041 GRCh37: 2:26950912-26950912
GRCh38: 2:26728044-26728044
3 KCNK3 NM_002246.3(KCNK3):c.575A>G (p.Tyr192Cys) SNV Pathogenic 60483 rs398123043 GRCh37: 2:26950826-26950826
GRCh38: 2:26727958-26727958
4 KCNK3 NM_002246.3(KCNK3):c.23C>A (p.Thr8Lys) SNV Pathogenic 426049 rs1085307438 GRCh37: 2:26915766-26915766
GRCh38: 2:26692898-26692898
5 KCNK3 NM_002246.3(KCNK3):c.608G>A (p.Gly203Asp) SNV Pathogenic 60479 rs398123039 GRCh37: 2:26950859-26950859
GRCh38: 2:26727991-26727991
6 KCNK3 NM_002246.3(KCNK3):c.365T>C (p.Leu122Pro) SNV Likely pathogenic 548009 rs1553387422 GRCh37: 2:26950616-26950616
GRCh38: 2:26727748-26727748
7 KCNK3 NM_002246.3(KCNK3):c.250_267dup (p.Phe84_Thr89dup) Duplication Uncertain significance 592111 rs1558592501 GRCh37: 2:26915990-26915991
GRCh38: 2:26693122-26693123
8 KCNK3 NM_002246.3(KCNK3):c.100G>A (p.Glu34Lys) SNV Uncertain significance 474316 rs1553383771 GRCh37: 2:26915843-26915843
GRCh38: 2:26692975-26692975
9 KCNK3 NM_002246.3(KCNK3):c.17T>C (p.Val6Ala) SNV Uncertain significance 474319 rs1226314697 GRCh37: 2:26915760-26915760
GRCh38: 2:26692892-26692892
10 KCNK3 NM_002246.3(KCNK3):c.1180G>A (p.Val394Met) SNV Uncertain significance 474317 rs1553387738 GRCh37: 2:26951431-26951431
GRCh38: 2:26728563-26728563
11 KCNK3 NM_002246.3(KCNK3):c.781C>A (p.Arg261Ser) SNV Uncertain significance 944759 GRCh37: 2:26951032-26951032
GRCh38: 2:26728164-26728164
12 KCNK3 NM_002246.3(KCNK3):c.172G>A (p.Gly58Ser) SNV Uncertain significance 474318 rs753384871 GRCh37: 2:26915915-26915915
GRCh38: 2:26693047-26693047
13 KCNK3 NM_002246.3(KCNK3):c.844A>G (p.Thr282Ala) SNV Uncertain significance 575685 rs779537390 GRCh37: 2:26951095-26951095
GRCh38: 2:26728227-26728227
14 KCNK3 NM_002246.3(KCNK3):c.1169G>A (p.Arg390His) SNV Uncertain significance 576185 rs868278570 GRCh37: 2:26951420-26951420
GRCh38: 2:26728552-26728552
15 KCNK3 NM_002246.3(KCNK3):c.547C>T (p.His183Tyr) SNV Uncertain significance 578932 rs1558604738 GRCh37: 2:26950798-26950798
GRCh38: 2:26727930-26727930
16 KCNK3 NM_002246.3(KCNK3):c.834C>A (p.Ser278Arg) SNV Uncertain significance 580390 rs750738078 GRCh37: 2:26951085-26951085
GRCh38: 2:26728217-26728217
17 KCNK3 NM_002246.3(KCNK3):c.646_651dup (p.Thr216_Gln217dup) Duplication Uncertain significance 580894 rs1558604795 GRCh37: 2:26950892-26950893
GRCh38: 2:26728024-26728025
18 KCNK3 NM_002246.3(KCNK3):c.283+6G>T SNV Uncertain significance 658020 rs369557396 GRCh37: 2:26916032-26916032
GRCh38: 2:26693164-26693164
19 KCNK3 NM_002246.3(KCNK3):c.1067C>A (p.Thr356Lys) SNV Uncertain significance 864183 GRCh37: 2:26951318-26951318
GRCh38: 2:26728450-26728450
20 KCNK3 NM_002246.3(KCNK3):c.952C>T (p.Arg318Cys) SNV Uncertain significance 618695 rs780914900 GRCh37: 2:26951203-26951203
GRCh38: 2:26728335-26728335
21 KCNK3 NM_002246.3(KCNK3):c.946A>G (p.Lys316Glu) SNV Uncertain significance 1002871 GRCh37: 2:26951197-26951197
GRCh38: 2:26728329-26728329
22 KCNK3 NM_002246.3(KCNK3):c.1094G>A (p.Gly365Glu) SNV Uncertain significance 1006500 GRCh37: 2:26951345-26951345
GRCh38: 2:26728477-26728477
23 KCNK3 NM_002246.3(KCNK3):c.544G>A (p.Glu182Lys) SNV Uncertain significance 60482 rs398123042 GRCh37: 2:26950795-26950795
GRCh38: 2:26727927-26727927
24 KCNK3 NM_002246.3(KCNK3):c.991C>T (p.Arg331Trp) SNV Uncertain significance 1013806 GRCh37: 2:26951242-26951242
GRCh38: 2:26728374-26728374
25 KCNK3 NM_002246.3(KCNK3):c.28G>A (p.Ala10Thr) SNV Uncertain significance 1018829 GRCh37: 2:26915771-26915771
GRCh38: 2:26692903-26692903
26 KCNK3 NM_002246.3(KCNK3):c.1162A>G (p.Met388Val) SNV Uncertain significance 1023521 GRCh37: 2:26951413-26951413
GRCh38: 2:26728545-26728545
27 KCNK3 NM_002246.3(KCNK3):c.967T>A (p.Tyr323Asn) SNV Uncertain significance 862866 GRCh37: 2:26951218-26951218
GRCh38: 2:26728350-26728350
28 KCNK3 NM_002246.3(KCNK3):c.746T>C (p.Met249Thr) SNV Uncertain significance 944079 GRCh37: 2:26950997-26950997
GRCh38: 2:26728129-26728129
29 KCNK3 NM_002246.3(KCNK3):c.872C>T (p.Ala291Val) SNV Uncertain significance 948244 GRCh37: 2:26951123-26951123
GRCh38: 2:26728255-26728255
30 KCNK3 NM_002246.3(KCNK3):c.827G>A (p.Gly276Asp) SNV Uncertain significance 952122 GRCh37: 2:26951078-26951078
GRCh38: 2:26728210-26728210
31 KCNK3 NM_002246.3(KCNK3):c.832A>T (p.Ser278Cys) SNV Uncertain significance 541325 rs368524386 GRCh37: 2:26951083-26951083
GRCh38: 2:26728215-26728215
32 KCNK3 NM_002246.3(KCNK3):c.853G>A (p.Ala285Thr) SNV Uncertain significance 935310 GRCh37: 2:26951104-26951104
GRCh38: 2:26728236-26728236
33 KCNK3 NM_002246.3(KCNK3):c.202C>T (p.Arg68Cys) SNV Uncertain significance 962756 GRCh37: 2:26915945-26915945
GRCh38: 2:26693077-26693077
34 KCNK3 NM_002246.3(KCNK3):c.275C>T (p.Thr92Ile) SNV Uncertain significance 811790 rs1572598853 GRCh37: 2:26916018-26916018
GRCh38: 2:26693150-26693150
35 KCNK3 NM_002246.3(KCNK3):c.1128G>A (p.Thr376=) SNV Uncertain significance 645379 rs760241147 GRCh37: 2:26951379-26951379
GRCh38: 2:26728511-26728511
36 KCNK3 NM_002246.3(KCNK3):c.618G>A (p.Val206=) SNV Uncertain significance 648112 rs536179160 GRCh37: 2:26950869-26950869
GRCh38: 2:26728001-26728001
37 KCNK3 NM_002246.3(KCNK3):c.785C>T (p.Ala262Val) SNV Uncertain significance 653289 rs1341257541 GRCh37: 2:26951036-26951036
GRCh38: 2:26728168-26728168
38 KCNK3 NM_002246.3(KCNK3):c.903G>A (p.Ala301=) SNV Uncertain significance 654608 rs1572616675 GRCh37: 2:26951154-26951154
GRCh38: 2:26728286-26728286
39 KCNK3 NM_002246.3(KCNK3):c.456C>T (p.Ala152=) SNV Likely benign 704086 rs112956865 GRCh37: 2:26950707-26950707
GRCh38: 2:26727839-26727839
40 KCNK3 NM_002246.3(KCNK3):c.1140C>G (p.Ser380Arg) SNV Likely benign 704801 rs753377260 GRCh37: 2:26951391-26951391
GRCh38: 2:26728523-26728523
41 KCNK3 NM_002246.3(KCNK3):c.120G>A (p.Arg40=) SNV Likely benign 794692 rs1022064324 GRCh37: 2:26915863-26915863
GRCh38: 2:26692995-26692995
42 KCNK3 NM_002246.3(KCNK3):c.366C>T (p.Leu122=) SNV Likely benign 474320 rs61736657 GRCh37: 2:26950617-26950617
GRCh38: 2:26727749-26727749
43 KCNK3 NM_002246.3(KCNK3):c.1097C>T (p.Ala366Val) SNV Likely benign 811685 rs773773071 GRCh37: 2:26951348-26951348
GRCh38: 2:26728480-26728480
44 KCNK3 NM_002246.3(KCNK3):c.423C>A (p.His141Gln) SNV Likely benign 474321 rs151228365 GRCh37: 2:26950674-26950674
GRCh38: 2:26727806-26727806
45 KCNK3 NM_002246.3(KCNK3):c.1014G>A (p.Thr338=) SNV Likely benign 541326 rs375930383 GRCh37: 2:26951265-26951265
GRCh38: 2:26728397-26728397
46 KCNK3 NM_002246.3(KCNK3):c.953G>A (p.Arg318His) SNV Benign 569441 rs150626749 GRCh37: 2:26951204-26951204
GRCh38: 2:26728336-26728336
47 KCNK3 NM_002246.3(KCNK3):c.654G>T (p.Pro218=) SNV Benign 474322 rs34292597 GRCh37: 2:26950905-26950905
GRCh38: 2:26728037-26728037

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

72
# 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

3 CDC
7 CNVD
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10 dbSNP
11 DGIdb
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30 HMDB
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56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
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71 UMLS via Orphanet
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