MCID: PSD092
MIFTS: 36

Pseudohypoaldosteronism, Type Iie

Categories: Genetic diseases, Rare diseases, Cardiovascular diseases, Nephrological diseases

Aliases & Classifications for Pseudohypoaldosteronism, Type Iie

MalaCards integrated aliases for Pseudohypoaldosteronism, Type Iie:

Name: Pseudohypoaldosteronism, Type Iie 57 13 73
Pseudohypoaldosteronism Type 2e 59 29 6 40
Gordon Hyperkalemia-Hypertension Syndrome 53 25 59
Familial Hyperkalemic Hypertension 24 25 59
Pseudohypoaldosteronism Type 2 53 25 59
Gordon's Syndrome 25 29 6
Pha2e 57 59 75
Phaii 24 25 59
Pseudohypoaldosteronism Type Ii 24 25
Pseudohypoaldosteronism, Type 2 29 6
Chloride Shunt Syndrome 53 59
Pha2 53 59
Hyperkalemia-Hypertension Syndrome, Gordon Type 59
Hyperpotassemia and Hypertension, Familial 73
Hyperpotassemia and Hypertension Familial 53
Familial Hyperpotassemia and Hypertension 25
Mineralocorticoid Resistant Hyperkalemia 59
Familial Hypertensive Hyperkalemia 25
Pseudohypoaldosteronism, Type Iid 73
Pseudohypoaldosteronism, Type Ii 73
Spitzer-Weinstein Syndrome 59
Pseudohypoaldosteronism 2e 75
Hypertensive Hyperkalemia 59
Gordon’s Syndrome 24
Fhht 25

Characteristics:

Orphanet epidemiological data:

59
pseudohypoaldosteronism type 2
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: All ages; Age of death: adult;
pseudohypoaldosteronism type 2e
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide);

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
responsive to thiazide diuretics
21 patients from 17 kindreds reported (as of february 2012)
age at diagnosis 9 +/- 6 years
94% develop hypertension at 18 years of age or less


HPO:

32
pseudohypoaldosteronism, type iie:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 614496
UMLS via Orphanet 74 C1449844
ICD10 via Orphanet 34 I15.1
MedGen 42 C3469606
MeSH 44 D011546

Summaries for Pseudohypoaldosteronism, Type Iie

NIH Rare Diseases : 53 Psuedohypoaldosteronism type 2 is an inborn error of metabolism. It is characterized by high blood pressure, high levels of potassium in the body, and metabolic acidosis. It is caused by mutations in the WNK1 or WNK4 gene. Treatment may involve dietary restriction of sodium and hydrochlorothiazide.

MalaCards based summary : Pseudohypoaldosteronism, Type Iie, also known as pseudohypoaldosteronism type 2e, is related to pseudohypoaldosteronism, type iia and pseudohypoaldosteronism. An important gene associated with Pseudohypoaldosteronism, Type Iie is CUL3 (Cullin 3). Affiliated tissues include kidney, and related phenotypes are hypertension and muscle weakness

Genetics Home Reference : 25 Pseudohypoaldosteronism type 2 (PHA2) is caused by problems that affect regulation of the amount of sodium and potassium in the body. Sodium and potassium are important in the control of blood pressure, and their regulation occurs primarily in the kidneys.

UniProtKB/Swiss-Prot : 75 Pseudohypoaldosteronism 2E: An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics.

Description from OMIM: 614496
GeneReviews: NBK65707

Related Diseases for Pseudohypoaldosteronism, Type Iie

Graphical network of the top 20 diseases related to Pseudohypoaldosteronism, Type Iie:



Diseases related to Pseudohypoaldosteronism, Type Iie

Symptoms & Phenotypes for Pseudohypoaldosteronism, Type Iie

Symptoms via clinical synopsis from OMIM:

57
Cardiovascular Vascular:
hypertension

Laboratory Abnormalities:
hyperkalemia (7.5 +/- 0.9 mm)
hyperchloremia (mean 114 mm)

Metabolic Features:
hyperchloremic metabolic acidosis (hco3 15.5 +/- 2.0 mm)


Clinical features from OMIM:

614496

Human phenotypes related to Pseudohypoaldosteronism, Type Iie:

59 32 (show all 13)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertension 59 32 hallmark (90%) Very frequent (99-80%) HP:0000822
2 muscle weakness 59 32 occasional (7.5%) Occasional (29-5%) HP:0001324
3 nausea and vomiting 59 32 frequent (33%) Frequent (79-30%) HP:0002017
4 short stature 59 32 occasional (7.5%) Occasional (29-5%) HP:0004322
5 abnormality of dental enamel 59 32 occasional (7.5%) Occasional (29-5%) HP:0000682
6 hyperkalemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002153
7 periodic paralysis 59 32 occasional (7.5%) Occasional (29-5%) HP:0003768
8 abnormality of the dentition 59 Occasional (29-5%)
9 growth delay 59 Occasional (29-5%)
10 metabolic acidosis 32 HP:0001942
11 hyperchloremic metabolic acidosis 32 HP:0004918
12 pseudohypoaldosteronism 32 HP:0008242
13 hyperchloremia 32 HP:0011423

GenomeRNAi Phenotypes related to Pseudohypoaldosteronism, Type Iie according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Synthetic lethal with c-Myc after tamoxifen stimulation GR00215-A 8.62 CUL3 KLHL3

Drugs & Therapeutics for Pseudohypoaldosteronism, Type Iie

Search Clinical Trials , NIH Clinical Center for Pseudohypoaldosteronism, Type Iie

Genetic Tests for Pseudohypoaldosteronism, Type Iie

Genetic tests related to Pseudohypoaldosteronism, Type Iie:

# Genetic test Affiliating Genes
1 Pseudohypoaldosteronism Type 2e 29 CUL3
2 Pseudohypoaldosteronism, Type 2 29
3 Gordon's Syndrome 29 PIEZO2

Anatomical Context for Pseudohypoaldosteronism, Type Iie

MalaCards organs/tissues related to Pseudohypoaldosteronism, Type Iie:

41
Kidney

Publications for Pseudohypoaldosteronism, Type Iie

Articles related to Pseudohypoaldosteronism, Type Iie:

# Title Authors Year
1
Mechanisms and controversies in mutant Cul3-mediated Familial Hyperkalemic Hypertension. ( 29361671 )
2018
2
A novel mutation in KLHL3 gene causes familial hyperkalemic hypertension. ( 27026694 )
2016
3
KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron. ( 22406640 )
2012
4
Syndromes of impaired ion handling in the distal nephron: pseudohypoaldosteronism and familial hyperkalemic hypertension. ( 22450343 )
2012
5
WNK4 enhances TRPV5-mediated calcium transport: potential role in hypercalciuria of familial hyperkalemic hypertension caused by gene mutation of WNK4. ( 17018846 )
2007
6
Familial hyperkalemic hypertension: phenotypic analysis in a large family with the WNK1 deletion mutation. ( 12727582 )
2003

Variations for Pseudohypoaldosteronism, Type Iie

UniProtKB/Swiss-Prot genetic disease variations for Pseudohypoaldosteronism, Type Iie:

75
# Symbol AA change Variation ID SNP ID
1 CUL3 p.Asp413Gly VAR_067532 rs199469656
2 CUL3 p.Lys459Arg VAR_067533 rs199469658

ClinVar genetic disease variations for Pseudohypoaldosteronism, Type Iie:

6
(show top 50) (show all 514)
# Gene Variation Type Significance SNP ID Assembly Location
1 CUL3 CUL3, IVS8, A-G, -26 single nucleotide variant Pathogenic
2 CUL3 CUL3, IVS8, T-G, -28 single nucleotide variant Pathogenic
3 CUL3 CUL3, IVS8, T-G, -12 single nucleotide variant Pathogenic
4 CUL3 CUL3, IVS8, T-A, -5 single nucleotide variant Pathogenic
5 CUL3 CUL3, IVS8, C-T, -3 single nucleotide variant Pathogenic
6 CUL3 CUL3, IVS8, G-A, -1 single nucleotide variant Pathogenic
7 CUL3 NM_003590.4(CUL3): c.1238A> G (p.Asp413Gly) single nucleotide variant Pathogenic rs199469656 GRCh37 Chromosome 2, 225368508: 225368508
8 CUL3 NM_003590.4(CUL3): c.1238A> G (p.Asp413Gly) single nucleotide variant Pathogenic rs199469656 GRCh38 Chromosome 2, 224503791: 224503791
9 KLHL3 NM_017415.2(KLHL3): c.965T> G (p.Phe322Cys) single nucleotide variant Pathogenic rs199469639 GRCh37 Chromosome 5, 136975605: 136975605
10 KLHL3 NM_017415.2(KLHL3): c.965T> G (p.Phe322Cys) single nucleotide variant Pathogenic rs199469639 GRCh38 Chromosome 5, 137639916: 137639916
11 KLHL3 NM_017415.2(KLHL3): c.1229C> T (p.Ser410Leu) single nucleotide variant Pathogenic rs199469641 GRCh37 Chromosome 5, 136973075: 136973075
12 KLHL3 NM_017415.2(KLHL3): c.1229C> T (p.Ser410Leu) single nucleotide variant Pathogenic rs199469641 GRCh38 Chromosome 5, 137637386: 137637386
13 KLHL3 NM_017415.2(KLHL3): c.1583G> A (p.Arg528His) single nucleotide variant Pathogenic rs199469636 GRCh37 Chromosome 5, 136963994: 136963994
14 KLHL3 NM_017415.2(KLHL3): c.1583G> A (p.Arg528His) single nucleotide variant Pathogenic rs199469636 GRCh38 Chromosome 5, 137628305: 137628305
15 KLHL3 NM_017415.2(KLHL3): c.718C> T (p.Arg240Ter) single nucleotide variant Pathogenic rs199469638 GRCh37 Chromosome 5, 136997639: 136997639
16 KLHL3 NM_017415.2(KLHL3): c.718C> T (p.Arg240Ter) single nucleotide variant Pathogenic rs199469638 GRCh38 Chromosome 5, 137661950: 137661950
17 KLHL3 NM_017415.2(KLHL3): c.1007G> T (p.Arg336Ile) single nucleotide variant Pathogenic rs199469640 GRCh37 Chromosome 5, 136975563: 136975563
18 KLHL3 NM_017415.2(KLHL3): c.1007G> T (p.Arg336Ile) single nucleotide variant Pathogenic rs199469640 GRCh38 Chromosome 5, 137639874: 137639874
19 KLHL3 NM_017415.2(KLHL3): c.1670A> G (p.Tyr557Cys) single nucleotide variant Pathogenic rs199469645 GRCh37 Chromosome 5, 136961507: 136961507
20 KLHL3 NM_017415.2(KLHL3): c.1670A> G (p.Tyr557Cys) single nucleotide variant Pathogenic rs199469645 GRCh38 Chromosome 5, 137625818: 137625818
21 KLHL3 NM_017415.2(KLHL3): c.1582C> T (p.Arg528Cys) single nucleotide variant Pathogenic rs199469635 GRCh37 Chromosome 5, 136963995: 136963995
22 KLHL3 NM_017415.2(KLHL3): c.1582C> T (p.Arg528Cys) single nucleotide variant Pathogenic rs199469635 GRCh38 Chromosome 5, 137628306: 137628306
23 KLHL3 NM_017415.2(KLHL3): c.1298G> A (p.Ser433Asn) single nucleotide variant Pathogenic rs199469632 GRCh37 Chromosome 5, 136973006: 136973006
24 KLHL3 NM_017415.2(KLHL3): c.1298G> A (p.Ser433Asn) single nucleotide variant Pathogenic rs199469632 GRCh38 Chromosome 5, 137637317: 137637317
25 CUL3 NM_003590.4(CUL3): c.1207-12T> G single nucleotide variant Pathogenic rs199469651 GRCh37 Chromosome 2, 225368551: 225368551
26 CUL3 NM_003590.4(CUL3): c.1207-12T> G single nucleotide variant Pathogenic rs199469651 GRCh38 Chromosome 2, 224503834: 224503834
27 CUL3 NM_003590.4(CUL3): c.1207-1G> A single nucleotide variant Pathogenic rs199469654 GRCh37 Chromosome 2, 225368540: 225368540
28 CUL3 NM_003590.4(CUL3): c.1207-1G> A single nucleotide variant Pathogenic rs199469654 GRCh38 Chromosome 2, 224503823: 224503823
29 CUL3 NM_003590.4(CUL3): c.1207-26A> G single nucleotide variant Pathogenic rs199469650 GRCh37 Chromosome 2, 225368565: 225368565
30 CUL3 NM_003590.4(CUL3): c.1207-26A> G single nucleotide variant Pathogenic rs199469650 GRCh38 Chromosome 2, 224503848: 224503848
31 CUL3 NM_003590.4(CUL3): c.1207-28T> G single nucleotide variant Pathogenic rs199469649 GRCh37 Chromosome 2, 225368567: 225368567
32 CUL3 NM_003590.4(CUL3): c.1207-28T> G single nucleotide variant Pathogenic rs199469649 GRCh38 Chromosome 2, 224503850: 224503850
33 CUL3 NM_003590.4(CUL3): c.1207-3C> T single nucleotide variant Pathogenic rs199469653 GRCh37 Chromosome 2, 225368542: 225368542
34 CUL3 NM_003590.4(CUL3): c.1207-3C> T single nucleotide variant Pathogenic rs199469653 GRCh38 Chromosome 2, 224503825: 224503825
35 CUL3 NM_003590.4(CUL3): c.1207-5T> A single nucleotide variant Pathogenic rs199469652 GRCh37 Chromosome 2, 225368544: 225368544
36 CUL3 NM_003590.4(CUL3): c.1207-5T> A single nucleotide variant Pathogenic rs199469652 GRCh38 Chromosome 2, 224503827: 224503827
37 CUL3 NM_003590.4(CUL3): c.1236G> A (p.Leu412=) single nucleotide variant Pathogenic rs199469655 GRCh37 Chromosome 2, 225368510: 225368510
38 CUL3 NM_003590.4(CUL3): c.1236G> A (p.Leu412=) single nucleotide variant Pathogenic rs199469655 GRCh38 Chromosome 2, 224503793: 224503793
39 CUL3 NM_003590.4(CUL3): c.1376A> G (p.Lys459Arg) single nucleotide variant Pathogenic rs199469658 GRCh37 Chromosome 2, 225368370: 225368370
40 CUL3 NM_003590.4(CUL3): c.1376A> G (p.Lys459Arg) single nucleotide variant Pathogenic rs199469658 GRCh38 Chromosome 2, 224503653: 224503653
41 CUL3 NM_003590.4(CUL3): c.1376_1377+4delAGGTAA deletion Pathogenic rs199469657 GRCh37 Chromosome 2, 225368365: 225368370
42 CUL3 NM_003590.4(CUL3): c.1376_1377+4delAGGTAA deletion Pathogenic rs199469657 GRCh38 Chromosome 2, 224503648: 224503653
43 CUL3 NM_003590.4(CUL3): c.1376_1377insG (p.Thr460Aspfs) insertion Pathogenic rs199469659 GRCh37 Chromosome 2, 225368369: 225368369
44 CUL3 NM_003590.4(CUL3): c.1376_1377insG (p.Thr460Aspfs) insertion Pathogenic rs199469659 GRCh38 Chromosome 2, 224503652: 224503652
45 CUL3 NM_003590.4(CUL3): c.1377+1G> C single nucleotide variant Pathogenic rs199469660 GRCh37 Chromosome 2, 225368368: 225368368
46 CUL3 NM_003590.4(CUL3): c.1377+1G> C single nucleotide variant Pathogenic rs199469660 GRCh38 Chromosome 2, 224503651: 224503651
47 CUL3 NM_003590.4(CUL3): c.1377+3A> G single nucleotide variant Pathogenic rs199469661 GRCh37 Chromosome 2, 225368366: 225368366
48 CUL3 NM_003590.4(CUL3): c.1377+3A> G single nucleotide variant Pathogenic rs199469661 GRCh38 Chromosome 2, 224503649: 224503649
49 KLHL3 NM_017415.2(KLHL3): c.1410G> A (p.Trp470Ter) single nucleotide variant Pathogenic rs199469644 GRCh37 Chromosome 5, 136969766: 136969766
50 KLHL3 NM_017415.2(KLHL3): c.1410G> A (p.Trp470Ter) single nucleotide variant Pathogenic rs199469644 GRCh38 Chromosome 5, 137634077: 137634077

Expression for Pseudohypoaldosteronism, Type Iie

Search GEO for disease gene expression data for Pseudohypoaldosteronism, Type Iie.

Pathways for Pseudohypoaldosteronism, Type Iie

GO Terms for Pseudohypoaldosteronism, Type Iie

Cellular components related to Pseudohypoaldosteronism, Type Iie according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Cul3-RING ubiquitin ligase complex GO:0031463 8.62 CUL3 KLHL3

Biological processes related to Pseudohypoaldosteronism, Type Iie according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein ubiquitination GO:0016567 9.16 CUL3 KLHL3
2 post-translational protein modification GO:0043687 8.96 CUL3 KLHL3
3 ubiquitin-dependent protein catabolic process GO:0006511 8.62 CUL3 KLHL3

Molecular functions related to Pseudohypoaldosteronism, Type Iie according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ubiquitin-protein transferase activity GO:0004842 8.62 CUL3 KLHL3

Sources for Pseudohypoaldosteronism, Type Iie

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
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45 MESH via Orphanet
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62 PubMed
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69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
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73 UMLS
74 UMLS via Orphanet
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