MCID: PSD092
MIFTS: 37

Pseudohypoaldosteronism, Type Iie

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

Aliases & Classifications for Pseudohypoaldosteronism, Type Iie

MalaCards integrated aliases for Pseudohypoaldosteronism, Type Iie:

Name: Pseudohypoaldosteronism, Type Iie 53 13 69
Gordon Hyperkalemia-Hypertension Syndrome 49 24 55
Familial Hyperkalemic Hypertension 23 24 55
Pseudohypoaldosteronism Type 2 49 24 55
Pha2e 53 55 71
Phaii 23 24 55
Pseudohypoaldosteronism Type Ii 23 24
Pseudohypoaldosteronism Type 2e 55 28
Chloride Shunt Syndrome 49 55
Gordon's Syndrome 24 28
Pha2 49 55
Hyperkalemia-Hypertension Syndrome, Gordon Type 55
Hyperpotassemia and Hypertension, Familial 69
Hyperpotassemia and Hypertension Familial 49
Familial Hyperpotassemia and Hypertension 24
Mineralocorticoid Resistant Hyperkalemia 55
Familial Hypertensive Hyperkalemia 24
Pseudohypoaldosteronism, Type Iid 69
Pseudohypoaldosteronism, Type Ii 69
Pseudohypoaldosteronism, Type 2 28
Spitzer-Weinstein Syndrome 55
Pseudohypoaldosteronism 2e 71
Hypertensive Hyperkalemia 55
Gordon’s Syndrome 23
Fhht 24

Characteristics:

Orphanet epidemiological data:

55
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:

53
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:

31
pseudohypoaldosteronism, type iie:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 53 614496
UMLS via Orphanet 70 C1449844
ICD10 via Orphanet 33 I15.1
MedGen 39 C3469606
MeSH 41 D011546

Summaries for Pseudohypoaldosteronism, Type Iie

NIH Rare Diseases : 49 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. Last updated: 12/2/2011

MalaCards based summary : Pseudohypoaldosteronism, Type Iie, also known as gordon hyperkalemia-hypertension syndrome, is related to pseudohypoaldosteronism, type iia and pseudohypoaldosteronism, and has symptoms including abnormality of dental enamel, hypertension and muscle weakness. An important gene associated with Pseudohypoaldosteronism, Type Iie is CUL3 (Cullin 3). Affiliated tissues include kidney, and related phenotype is Synthetic lethal with c-Myc after tamoxifen stimulation.

Genetics Home Reference : 24 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 : 71 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:

53
CardiovascularVascular:
hypertension

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

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


Clinical features from OMIM:

614496

Human phenotypes related to Pseudohypoaldosteronism, Type Iie:

55 31 (show all 13)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormality of dental enamel 55 31 occasional (7.5%) Occasional (29-5%) HP:0000682
2 hypertension 55 31 hallmark (90%) Very frequent (99-80%) HP:0000822
3 muscle weakness 55 31 occasional (7.5%) Occasional (29-5%) HP:0001324
4 nausea and vomiting 55 31 frequent (33%) Frequent (79-30%) HP:0002017
5 hyperkalemia 55 31 hallmark (90%) Very frequent (99-80%) HP:0002153
6 periodic paralysis 55 31 occasional (7.5%) Occasional (29-5%) HP:0003768
7 short stature 55 31 occasional (7.5%) Occasional (29-5%) HP:0004322
8 abnormality of the dentition 55 Occasional (29-5%)
9 growth delay 55 Occasional (29-5%)
10 metabolic acidosis 31 HP:0001942
11 hyperchloremic metabolic acidosis 31 HP:0004918
12 pseudohypoaldosteronism 31 HP:0008242
13 hyperchloremia 31 HP:0011423

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

25
# 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 28 CUL3
2 Pseudohypoaldosteronism, Type 2 28
3 Gordon's Syndrome 28 PIEZO2

Anatomical Context for Pseudohypoaldosteronism, Type Iie

MalaCards organs/tissues related to Pseudohypoaldosteronism, Type Iie:

38
Kidney

Publications for Pseudohypoaldosteronism, Type Iie

Articles related to Pseudohypoaldosteronism, Type Iie:

# Title Authors Year
1
A novel mutation in KLHL3 gene causes familial hyperkalemic hypertension. ( 27026694 )
2016
2
KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron. ( 22406640 )
2012
3
Syndromes of impaired ion handling in the distal nephron: pseudohypoaldosteronism and familial hyperkalemic hypertension. ( 22450343 )
2012
4
WNK4 enhances TRPV5-mediated calcium transport: potential role in hypercalciuria of familial hyperkalemic hypertension caused by gene mutation of WNK4. ( 17018846 )
2007
5
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:

71
# 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 all 48)
# 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 KLHL3 NM_017415.2(KLHL3): c.965T> G (p.Phe322Cys) single nucleotide variant Pathogenic rs199469639 GRCh37 Chromosome 5, 136975605: 136975605
9 KLHL3 NM_017415.2(KLHL3): c.1229C> T (p.Ser410Leu) single nucleotide variant Pathogenic rs199469641 GRCh37 Chromosome 5, 136973075: 136973075
10 KLHL3 NM_017415.2(KLHL3): c.1583G> A (p.Arg528His) single nucleotide variant Pathogenic rs199469636 GRCh37 Chromosome 5, 136963994: 136963994
11 KLHL3 NM_017415.2(KLHL3): c.718C> T (p.Arg240Ter) single nucleotide variant Pathogenic rs199469638 GRCh37 Chromosome 5, 136997639: 136997639
12 KLHL3 NM_017415.2(KLHL3): c.1007G> T (p.Arg336Ile) single nucleotide variant Pathogenic rs199469640 GRCh37 Chromosome 5, 136975563: 136975563
13 KLHL3 NM_017415.2(KLHL3): c.1670A> G (p.Tyr557Cys) single nucleotide variant Pathogenic rs199469645 GRCh37 Chromosome 5, 136961507: 136961507
14 KLHL3 NM_017415.2(KLHL3): c.1582C> T (p.Arg528Cys) single nucleotide variant Pathogenic rs199469635 GRCh37 Chromosome 5, 136963995: 136963995
15 KLHL3 NM_017415.2(KLHL3): c.1298G> A (p.Ser433Asn) single nucleotide variant Pathogenic rs199469632 GRCh37 Chromosome 5, 136973006: 136973006
16 CUL3 NM_003590.4(CUL3): c.1207-12T> G single nucleotide variant Pathogenic rs199469651 GRCh37 Chromosome 2, 225368551: 225368551
17 CUL3 NM_003590.4(CUL3): c.1207-1G> A single nucleotide variant Pathogenic rs199469654 GRCh37 Chromosome 2, 225368540: 225368540
18 CUL3 NM_003590.4(CUL3): c.1207-26A> G single nucleotide variant Pathogenic rs199469650 GRCh37 Chromosome 2, 225368565: 225368565
19 CUL3 NM_003590.4(CUL3): c.1207-28T> G single nucleotide variant Pathogenic rs199469649 GRCh37 Chromosome 2, 225368567: 225368567
20 CUL3 NM_003590.4(CUL3): c.1207-3C> T single nucleotide variant Pathogenic rs199469653 GRCh37 Chromosome 2, 225368542: 225368542
21 CUL3 NM_003590.4(CUL3): c.1207-5T> A single nucleotide variant Pathogenic rs199469652 GRCh37 Chromosome 2, 225368544: 225368544
22 CUL3 NM_003590.4(CUL3): c.1236G> A (p.Leu412=) single nucleotide variant Pathogenic rs199469655 GRCh37 Chromosome 2, 225368510: 225368510
23 CUL3 NM_003590.4(CUL3): c.1376A> G (p.Lys459Arg) single nucleotide variant Pathogenic rs199469658 GRCh37 Chromosome 2, 225368370: 225368370
24 CUL3 NM_003590.4(CUL3): c.1376_1377+4delAGGTAA deletion Pathogenic rs199469657 GRCh37 Chromosome 2, 225368365: 225368370
25 CUL3 NM_003590.4(CUL3): c.1376_1377insG (p.Thr460Aspfs) insertion Pathogenic rs199469659 GRCh37 Chromosome 2, 225368369: 225368369
26 CUL3 NM_003590.4(CUL3): c.1377+1G> C single nucleotide variant Pathogenic rs199469660 GRCh37 Chromosome 2, 225368368: 225368368
27 CUL3 NM_003590.4(CUL3): c.1377+3A> G single nucleotide variant Pathogenic rs199469661 GRCh37 Chromosome 2, 225368366: 225368366
28 KLHL3 NM_017415.2(KLHL3): c.1410G> A (p.Trp470Ter) single nucleotide variant Pathogenic rs199469644 GRCh37 Chromosome 5, 136969766: 136969766
29 KLHL3 NM_017415.2(KLHL3): c.721delC (p.Leu241Phefs) deletion Pathogenic rs199469647 GRCh37 Chromosome 5, 136997636: 136997636
30 KLHL3 NM_017415.2(KLHL3): c.753+1G> A single nucleotide variant Pathogenic rs199469648 GRCh37 Chromosome 5, 136997603: 136997603
31 KLHL3 NM_017415.2(KLHL3): c.1019C> T (p.Ala340Val) single nucleotide variant Pathogenic rs199469628 GRCh37 Chromosome 5, 136975551: 136975551
32 KLHL3 NM_017415.2(KLHL3): c.1480G> A (p.Ala494Thr) single nucleotide variant Pathogenic rs199469633 GRCh37 Chromosome 5, 136964097: 136964097
33 KLHL3 NM_017415.2(KLHL3): c.230C> A (p.Ala77Glu) single nucleotide variant Pathogenic rs199469623 GRCh37 Chromosome 5, 137045450: 137045450
34 KLHL3 NM_017415.2(KLHL3): c.491G> T (p.Cys164Phe) single nucleotide variant Pathogenic rs199469626 GRCh37 Chromosome 5, 137028009: 137028009
35 KLHL3 NM_017415.2(KLHL3): c.254A> C (p.Glu85Ala) single nucleotide variant Pathogenic rs199469625 GRCh37 Chromosome 5, 137034085: 137034085
36 KLHL3 NM_017415.2(KLHL3): c.1160T> C (p.Leu387Pro) single nucleotide variant Pathogenic rs199469630 GRCh37 Chromosome 5, 136974701: 136974701
37 KLHL3 NM_017415.2(KLHL3): c.1280T> C (p.Met427Thr) single nucleotide variant Pathogenic rs199469642 GRCh37 Chromosome 5, 136973024: 136973024
38 KLHL3 NM_017415.2(KLHL3): c.232A> G (p.Met78Val) single nucleotide variant Pathogenic rs199469624 GRCh37 Chromosome 5, 137045448: 137045448
39 KLHL3 NM_017415.2(KLHL3): c.1501C> A (p.Pro501Thr) single nucleotide variant Pathogenic rs199469634 GRCh37 Chromosome 5, 136964076: 136964076
40 KLHL3 NM_017415.2(KLHL3): c.430C> T (p.Gln144Ter) single nucleotide variant Pathogenic rs199469637 GRCh37 Chromosome 5, 137028070: 137028070
41 KLHL3 NM_017415.2(KLHL3): c.926A> G (p.Gln309Arg) single nucleotide variant Pathogenic rs199469627 GRCh37 Chromosome 5, 136975644: 136975644
42 KLHL3 NM_017415.2(KLHL3): c.1151G> A (p.Arg384Gln) single nucleotide variant Pathogenic rs199469629 GRCh37 Chromosome 5, 136974710: 136974710
43 KLHL3 NM_017415.2(KLHL3): c.1292G> A (p.Arg431Gln) single nucleotide variant Pathogenic rs199469643 GRCh37 Chromosome 5, 136973012: 136973012
44 KLHL3 NM_017415.2(KLHL3): c.1723C> T (p.Arg575Trp) single nucleotide variant Pathogenic rs199469646 GRCh37 Chromosome 5, 136961454: 136961454
45 KLHL3 NM_017415.2(KLHL3): c.1295G> A (p.Ser432Asn) single nucleotide variant Pathogenic rs199469631 GRCh37 Chromosome 5, 136973009: 136973009
46 PIEZO2 NM_022068.3(PIEZO2): c.8238_8245delGACTAGAG (p.Trp2746Terfs) deletion Pathogenic rs724159993 GRCh37 Chromosome 18, 10671538: 10671545
47 PIEZO2 NM_022068.3(PIEZO2): c.8057G> A (p.Arg2686His) single nucleotide variant Pathogenic rs587777450 GRCh38 Chromosome 18, 10671729: 10671729
48 CUL3 NM_003590.4(CUL3): c.1377G> A (p.Lys459=) single nucleotide variant Likely pathogenic rs886038765 GRCh37 Chromosome 2, 225368369: 225368369

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 protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:0042787 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
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
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41 MeSH
42 MESH via Orphanet
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58 PubMed
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65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
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70 UMLS via Orphanet
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