PPH4
MCID: PLM121
MIFTS: 21

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 75 73
Primary Pulmonary Hypertension 4 29 6
Pph4 57 75
Hypertension, Pulmonary, Primary, Type 4 40

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

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


HPO:

32
pulmonary hypertension, primary, 4:
Onset and clinical course incomplete penetrance progressive
Inheritance autosomal dominant inheritance


Classifications:



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)

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). The drugs Spironolactone and Natriuretic Agents have been mentioned in the context of this disorder. Affiliated tissues include lung, heart and endothelial, and related phenotypes are arrhythmia and pulmonary arterial hypertension

UniProtKB/Swiss-Prot : 75 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

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Pulmonary Hypertension, Primary, 4:

32
# Description HPO Frequency HPO Source Accession
1 arrhythmia 32 occasional (7.5%) HP:0011675
2 pulmonary arterial hypertension 32 HP:0002092
3 increased pulmonary vascular resistance 32 HP:0005317

Drugs & Therapeutics for Pulmonary Hypertension, Primary, 4

Drugs for Pulmonary Hypertension, Primary, 4 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 17)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Spironolactone Approved Phase 4 52-01-7, 1952-01-7 5833
2 Natriuretic Agents Phase 4
3 diuretics Phase 4
4 Diuretics, Potassium Sparing Phase 4
5 Natriuretic Peptide, Brain Phase 4
6 Mineralocorticoids Phase 4
7 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 4
8 Mineralocorticoid Receptor Antagonists Phase 4
9 Hormone Antagonists Phase 4
10 Hormones Phase 4
11
Oxytocin Approved, Vet_approved Phase 3 50-56-6 439302 53477758
12
Ergonovine Approved Phase 3 60-79-7 443884
13
Lactitol Investigational Phase 3 585-86-4 3871
14 Laxatives Phase 3
15 Cathartics Phase 3
16 Gastrointestinal Agents Phase 3
17 Oxytocics Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Spironolactone Therapy in Chronic Stable Right HF Trial Recruiting NCT03344159 Phase 4 Spironolactone;Placebo
2 Ergometrine Versus Oxytocin in the Management of Atonic Post-partum Haemorrhage (PPH) in Women Delivered Vaginally Unknown status NCT02306733 Phase 3 Ergometrine;Oxytocin

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:

41
Lung, Heart, Endothelial

Publications for Pulmonary Hypertension, Primary, 4

Variations for Pulmonary Hypertension, Primary, 4

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

75
# 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

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

6 (show all 44)
# Gene Variation Type Significance SNP ID Assembly Location
1 KCNK3 NM_002246.2(KCNK3): c.608G> A (p.Gly203Asp) single nucleotide variant Pathogenic rs398123039 GRCh37 Chromosome 2, 26950859: 26950859
2 KCNK3 NM_002246.2(KCNK3): c.608G> A (p.Gly203Asp) single nucleotide variant Pathogenic rs398123039 GRCh38 Chromosome 2, 26727991: 26727991
3 KCNK3 NM_002246.2(KCNK3): c.289G> A (p.Gly97Arg) single nucleotide variant Pathogenic rs398123040 GRCh37 Chromosome 2, 26950540: 26950540
4 KCNK3 NM_002246.2(KCNK3): c.289G> A (p.Gly97Arg) single nucleotide variant Pathogenic rs398123040 GRCh38 Chromosome 2, 26727672: 26727672
5 KCNK3 NM_002246.2(KCNK3): c.661G> C (p.Val221Leu) single nucleotide variant Pathogenic rs398123041 GRCh37 Chromosome 2, 26950912: 26950912
6 KCNK3 NM_002246.2(KCNK3): c.661G> C (p.Val221Leu) single nucleotide variant Pathogenic rs398123041 GRCh38 Chromosome 2, 26728044: 26728044
7 KCNK3 NM_002246.2(KCNK3): c.544G> A (p.Glu182Lys) single nucleotide variant Pathogenic rs398123042 GRCh37 Chromosome 2, 26950795: 26950795
8 KCNK3 NM_002246.2(KCNK3): c.544G> A (p.Glu182Lys) single nucleotide variant Pathogenic rs398123042 GRCh38 Chromosome 2, 26727927: 26727927
9 KCNK3 NM_002246.2(KCNK3): c.575A> G (p.Tyr192Cys) single nucleotide variant Pathogenic rs398123043 GRCh37 Chromosome 2, 26950826: 26950826
10 KCNK3 NM_002246.2(KCNK3): c.575A> G (p.Tyr192Cys) single nucleotide variant Pathogenic rs398123043 GRCh38 Chromosome 2, 26727958: 26727958
11 KCNK3 NM_002246.2(KCNK3): c.23C> A (p.Thr8Lys) single nucleotide variant Pathogenic rs1085307438 GRCh37 Chromosome 2, 26915766: 26915766
12 KCNK3 NM_002246.2(KCNK3): c.23C> A (p.Thr8Lys) single nucleotide variant Pathogenic rs1085307438 GRCh38 Chromosome 2, 26692898: 26692898
13 KCNK3 NM_002246.2(KCNK3): c.17T> C (p.Val6Ala) single nucleotide variant Uncertain significance GRCh38 Chromosome 2, 26692892: 26692892
14 KCNK3 NM_002246.2(KCNK3): c.17T> C (p.Val6Ala) single nucleotide variant Uncertain significance GRCh37 Chromosome 2, 26915760: 26915760
15 KCNK3 NM_002246.2(KCNK3): c.172G> A (p.Gly58Ser) single nucleotide variant Uncertain significance rs753384871 GRCh37 Chromosome 2, 26915915: 26915915
16 KCNK3 NM_002246.2(KCNK3): c.172G> A (p.Gly58Ser) single nucleotide variant Uncertain significance rs753384871 GRCh38 Chromosome 2, 26693047: 26693047
17 KCNK3 NM_002246.2(KCNK3): c.654G> T (p.Pro218=) single nucleotide variant Benign rs34292597 GRCh37 Chromosome 2, 26950905: 26950905
18 KCNK3 NM_002246.2(KCNK3): c.654G> T (p.Pro218=) single nucleotide variant Benign rs34292597 GRCh38 Chromosome 2, 26728037: 26728037
19 KCNK3 NM_002246.2(KCNK3): c.366C> T (p.Leu122=) single nucleotide variant Likely benign rs61736657 GRCh37 Chromosome 2, 26950617: 26950617
20 KCNK3 NM_002246.2(KCNK3): c.366C> T (p.Leu122=) single nucleotide variant Likely benign rs61736657 GRCh38 Chromosome 2, 26727749: 26727749
21 KCNK3 NM_002246.2(KCNK3): c.423C> A (p.His141Gln) single nucleotide variant Likely benign rs151228365 GRCh37 Chromosome 2, 26950674: 26950674
22 KCNK3 NM_002246.2(KCNK3): c.423C> A (p.His141Gln) single nucleotide variant Likely benign rs151228365 GRCh38 Chromosome 2, 26727806: 26727806
23 KCNK3 NM_002246.2(KCNK3): c.1180G> A (p.Val394Met) single nucleotide variant Uncertain significance GRCh37 Chromosome 2, 26951431: 26951431
24 KCNK3 NM_002246.2(KCNK3): c.1180G> A (p.Val394Met) single nucleotide variant Uncertain significance GRCh38 Chromosome 2, 26728563: 26728563
25 KCNK3 NM_002246.2(KCNK3): c.100G> A (p.Glu34Lys) single nucleotide variant Uncertain significance GRCh37 Chromosome 2, 26915843: 26915843
26 KCNK3 NM_002246.2(KCNK3): c.100G> A (p.Glu34Lys) single nucleotide variant Uncertain significance GRCh38 Chromosome 2, 26692975: 26692975
27 KCNK3 NM_002246.2(KCNK3): c.832A> T (p.Ser278Cys) single nucleotide variant Uncertain significance rs368524386 GRCh37 Chromosome 2, 26951083: 26951083
28 KCNK3 NM_002246.2(KCNK3): c.832A> T (p.Ser278Cys) single nucleotide variant Uncertain significance rs368524386 GRCh38 Chromosome 2, 26728215: 26728215
29 KCNK3 NM_002246.2(KCNK3): c.1014G> A (p.Thr338=) single nucleotide variant Likely benign rs375930383 GRCh38 Chromosome 2, 26728397: 26728397
30 KCNK3 NM_002246.2(KCNK3): c.1014G> A (p.Thr338=) single nucleotide variant Likely benign rs375930383 GRCh37 Chromosome 2, 26951265: 26951265
31 KCNK3 NM_002246.2(KCNK3): c.365T> C (p.Leu122Pro) single nucleotide variant Likely pathogenic GRCh38 Chromosome 2, 26727748: 26727748
32 KCNK3 NM_002246.2(KCNK3): c.365T> C (p.Leu122Pro) single nucleotide variant Likely pathogenic GRCh37 Chromosome 2, 26950616: 26950616
33 KCNK3 NM_002246.2(KCNK3): c.834C> A (p.Ser278Arg) single nucleotide variant Uncertain significance rs750738078 GRCh38 Chromosome 2, 26728217: 26728217
34 KCNK3 NM_002246.2(KCNK3): c.834C> A (p.Ser278Arg) single nucleotide variant Uncertain significance rs750738078 GRCh37 Chromosome 2, 26951085: 26951085
35 KCNK3 NM_002246.2(KCNK3): c.953G> A (p.Arg318His) single nucleotide variant Uncertain significance rs150626749 GRCh38 Chromosome 2, 26728336: 26728336
36 KCNK3 NM_002246.2(KCNK3): c.953G> A (p.Arg318His) single nucleotide variant Uncertain significance rs150626749 GRCh37 Chromosome 2, 26951204: 26951204
37 KCNK3 NM_002246.2(KCNK3): c.547C> T (p.His183Tyr) single nucleotide variant Uncertain significance GRCh38 Chromosome 2, 26727930: 26727930
38 KCNK3 NM_002246.2(KCNK3): c.547C> T (p.His183Tyr) single nucleotide variant Uncertain significance GRCh37 Chromosome 2, 26950798: 26950798
39 KCNK3 NM_002246.2(KCNK3): c.646_651dup (p.Gln217_Pro218insThrGln) duplication Uncertain significance GRCh38 Chromosome 2, 26728029: 26728034
40 KCNK3 NM_002246.2(KCNK3): c.646_651dup (p.Gln217_Pro218insThrGln) duplication Uncertain significance GRCh37 Chromosome 2, 26950897: 26950902
41 KCNK3 NM_002246.2(KCNK3): c.844A> G (p.Thr282Ala) single nucleotide variant Uncertain significance rs779537390 GRCh38 Chromosome 2, 26728227: 26728227
42 KCNK3 NM_002246.2(KCNK3): c.844A> G (p.Thr282Ala) single nucleotide variant Uncertain significance rs779537390 GRCh37 Chromosome 2, 26951095: 26951095
43 KCNK3 NM_002246.2(KCNK3): c.1169G> A (p.Arg390His) single nucleotide variant Uncertain significance rs868278570 GRCh38 Chromosome 2, 26728552: 26728552
44 KCNK3 NM_002246.2(KCNK3): c.1169G> A (p.Arg390His) single nucleotide variant Uncertain significance rs868278570 GRCh37 Chromosome 2, 26951420: 26951420

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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