MCID: PSD093
MIFTS: 24

Pseudohypoaldosteronism, Type Iid

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

Aliases & Classifications for Pseudohypoaldosteronism, Type Iid

MalaCards integrated aliases for Pseudohypoaldosteronism, Type Iid:

Name: Pseudohypoaldosteronism, Type Iid 57 13 73
Pseudohypoaldosteronism Type 2d 59 29 6 40
Pha2d 57 59 75
Familial Hyperkalemic Hypertension; Fhht 57
Familial Hyperkalemic Hypertension 57
Pseudohypoaldosteronism 2d 75
Fhht 57

Characteristics:

Orphanet epidemiological data:

59
pseudohypoaldosteronism type 2d
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide);

OMIM:

57
Inheritance:
autosomal dominant
autosomal recessive

Miscellaneous:
40 patients in 16 dominant kindreds reported (as of february 2012)
14 patients in 8 recessive kindreds reported (as of february 2012)
less than 20% have onset at 18 years of age or less (dominant and recessive)
age at diagnosis 24 +/- 18 years for dominant disease
age at diagnosis 26 +/- 14 years for recessive disease
responsive to thiazide diuretics


HPO:

32
pseudohypoaldosteronism, type iid:
Inheritance autosomal dominant inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 614495
Orphanet 59 ORPHA300525
ICD10 via Orphanet 34 I15.1
MedGen 42 C3469605
MeSH 44 D011546
UMLS 73 C3469605

Summaries for Pseudohypoaldosteronism, Type Iid

OMIM : 57 Familial hyperkalemic hypertension, also known as type II pseudohypoaldosteronism (PHAII) or Gordon syndrome, is a rare autosomal dominant disease in which a net positive sodium ion balance is associated with renal potassium ion retention, resulting in hypertension, hyperkalemia, and hyperchloremic metabolic acidosis (summary by Louis-Dit-Picard et al., 2012). (614495)

MalaCards based summary : Pseudohypoaldosteronism, Type Iid, also known as pseudohypoaldosteronism type 2d, is related to pseudohypoaldosteronism, type iie. An important gene associated with Pseudohypoaldosteronism, Type Iid is KLHL3 (Kelch Like Family Member 3). Related phenotypes are hypertension and hyperkalemia

UniProtKB/Swiss-Prot : 75 Pseudohypoaldosteronism 2D: A disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics. PHA2D inheritance is autosomal dominant or recessive.

Related Diseases for Pseudohypoaldosteronism, Type Iid

Diseases in the Pseudohypoaldosteronism family:

Pseudohypoaldosteronism, Type Iia Pseudohypoaldosteronism, Type I, Autosomal Dominant
Pseudohypoaldosteronism, Type I, Autosomal Recessive Pseudohypoaldosteronism, Type Iib
Pseudohypoaldosteronism, Type Iic Pseudohypoaldosteronism, Type Iid
Pseudohypoaldosteronism, Type Iie Transient Pseudohypoaldosteronism

Diseases related to Pseudohypoaldosteronism, Type Iid via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 pseudohypoaldosteronism, type iie 11.2

Symptoms & Phenotypes for Pseudohypoaldosteronism, Type Iid

Symptoms via clinical synopsis from OMIM:

57
Cardiovascular Vascular:
hypertension

Laboratory Abnormalities:
hyperkalemia (>6.2 mm in both dominant and recessive)
hyperchloremia (mean >110 mm in both dominant and recessive)

Metabolic Features:
hyperchloremic metabolic acidosis (hco3 17.2 +/- 2.5 mm, dominant)
hyperchloremic metabolic acidosis (hco3 17.6 +/- 1.5 mm, recessive)


Clinical features from OMIM:

614495

Human phenotypes related to Pseudohypoaldosteronism, Type Iid:

32
# Description HPO Frequency HPO Source Accession
1 hypertension 32 HP:0000822
2 hyperkalemia 32 HP:0002153
3 hyperchloremic metabolic acidosis 32 HP:0004918
4 pseudohypoaldosteronism 32 HP:0008242
5 hyperchloremia 32 HP:0011423

Drugs & Therapeutics for Pseudohypoaldosteronism, Type Iid

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

Genetic Tests for Pseudohypoaldosteronism, Type Iid

Genetic tests related to Pseudohypoaldosteronism, Type Iid:

# Genetic test Affiliating Genes
1 Pseudohypoaldosteronism Type 2d 29 KLHL3

Anatomical Context for Pseudohypoaldosteronism, Type Iid

Publications for Pseudohypoaldosteronism, Type Iid

Articles related to Pseudohypoaldosteronism, Type Iid:

# 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 Iid

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

75 (show all 32)
# Symbol AA change Variation ID SNP ID
1 KLHL3 p.Ala77Glu VAR_067501 rs199469623
2 KLHL3 p.Met78Val VAR_067502 rs199469624
3 KLHL3 p.Glu85Ala VAR_067503 rs199469625
4 KLHL3 p.Cys164Phe VAR_067504 rs199469626
5 KLHL3 p.Arg228Gly VAR_067505
6 KLHL3 p.Gln309Arg VAR_067506 rs199469627
7 KLHL3 p.Phe322Cys VAR_067507 rs199469639
8 KLHL3 p.Arg336Ile VAR_067508 rs199469640
9 KLHL3 p.Ala340Val VAR_067509 rs199469628
10 KLHL3 p.Val361Met VAR_067510
11 KLHL3 p.Arg362Trp VAR_067511 rs200892557
12 KLHL3 p.Arg384Gln VAR_067512 rs199469629
13 KLHL3 p.Arg384Trp VAR_067513 rs951676369
14 KLHL3 p.Leu387Pro VAR_067514 rs199469630
15 KLHL3 p.Ala398Val VAR_067515 rs387907155
16 KLHL3 p.Ser410Leu VAR_067516 rs199469641
17 KLHL3 p.Pro426Leu VAR_067517 rs387907156
18 KLHL3 p.Met427Thr VAR_067518 rs199469642
19 KLHL3 p.Arg431Gln VAR_067519 rs199469643
20 KLHL3 p.Ser432Asn VAR_067520 rs199469631
21 KLHL3 p.Ser433Gly VAR_067521
22 KLHL3 p.Ser433Asn VAR_067522 rs199469632
23 KLHL3 p.Ala494Thr VAR_067524 rs199469633
24 KLHL3 p.Gly500Val VAR_067525 rs746774345
25 KLHL3 p.Pro501Thr VAR_067526 rs199469634
26 KLHL3 p.Arg528Cys VAR_067527 rs199469635
27 KLHL3 p.Arg528His VAR_067528 rs199469636
28 KLHL3 p.Asn529Lys VAR_067529
29 KLHL3 p.Tyr557Cys VAR_067530 rs199469645
30 KLHL3 p.Arg575Trp VAR_067531 rs199469646
31 KLHL3 p.His498Tyr VAR_079630
32 KLHL3 p.Ser553Leu VAR_079631

ClinVar genetic disease variations for Pseudohypoaldosteronism, Type Iid:

6
(show all 24)
# Gene Variation Type Significance SNP ID Assembly Location
1 KLHL3 KLHL3, TRP470TER single nucleotide variant Pathogenic
2 KLHL3 NM_017415.2(KLHL3): c.965T> G (p.Phe322Cys) single nucleotide variant Pathogenic rs199469639 GRCh37 Chromosome 5, 136975605: 136975605
3 KLHL3 NM_017415.2(KLHL3): c.965T> G (p.Phe322Cys) single nucleotide variant Pathogenic rs199469639 GRCh38 Chromosome 5, 137639916: 137639916
4 KLHL3 NM_017415.2(KLHL3): c.1229C> T (p.Ser410Leu) single nucleotide variant Pathogenic rs199469641 GRCh37 Chromosome 5, 136973075: 136973075
5 KLHL3 NM_017415.2(KLHL3): c.1229C> T (p.Ser410Leu) single nucleotide variant Pathogenic rs199469641 GRCh38 Chromosome 5, 137637386: 137637386
6 KLHL3 NM_017415.2(KLHL3): c.1583G> A (p.Arg528His) single nucleotide variant Pathogenic rs199469636 GRCh37 Chromosome 5, 136963994: 136963994
7 KLHL3 NM_017415.2(KLHL3): c.1583G> A (p.Arg528His) single nucleotide variant Pathogenic rs199469636 GRCh38 Chromosome 5, 137628305: 137628305
8 KLHL3 NM_017415.2(KLHL3): c.718C> T (p.Arg240Ter) single nucleotide variant Pathogenic rs199469638 GRCh37 Chromosome 5, 136997639: 136997639
9 KLHL3 NM_017415.2(KLHL3): c.718C> T (p.Arg240Ter) single nucleotide variant Pathogenic rs199469638 GRCh38 Chromosome 5, 137661950: 137661950
10 KLHL3 NM_017415.2(KLHL3): c.1007G> T (p.Arg336Ile) single nucleotide variant Pathogenic rs199469640 GRCh37 Chromosome 5, 136975563: 136975563
11 KLHL3 NM_017415.2(KLHL3): c.1007G> T (p.Arg336Ile) single nucleotide variant Pathogenic rs199469640 GRCh38 Chromosome 5, 137639874: 137639874
12 KLHL3 NM_017415.2(KLHL3): c.1670A> G (p.Tyr557Cys) single nucleotide variant Pathogenic rs199469645 GRCh37 Chromosome 5, 136961507: 136961507
13 KLHL3 NM_017415.2(KLHL3): c.1670A> G (p.Tyr557Cys) single nucleotide variant Pathogenic rs199469645 GRCh38 Chromosome 5, 137625818: 137625818
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.1582C> T (p.Arg528Cys) single nucleotide variant Pathogenic rs199469635 GRCh38 Chromosome 5, 137628306: 137628306
16 KLHL3 NM_017415.2(KLHL3): c.1298G> A (p.Ser433Asn) single nucleotide variant Pathogenic rs199469632 GRCh37 Chromosome 5, 136973006: 136973006
17 KLHL3 NM_017415.2(KLHL3): c.1298G> A (p.Ser433Asn) single nucleotide variant Pathogenic rs199469632 GRCh38 Chromosome 5, 137637317: 137637317
18 KLHL3 NM_017415.2(KLHL3): c.1193C> T (p.Ala398Val) single nucleotide variant Pathogenic rs387907155 GRCh37 Chromosome 5, 136974668: 136974668
19 KLHL3 NM_017415.2(KLHL3): c.1193C> T (p.Ala398Val) single nucleotide variant Pathogenic rs387907155 GRCh38 Chromosome 5, 137638979: 137638979
20 KLHL3 KLHL3, ASN529LYS single nucleotide variant Pathogenic
21 KLHL3 NM_017415.2(KLHL3): c.1277C> T (p.Pro426Leu) single nucleotide variant Pathogenic rs387907156 GRCh37 Chromosome 5, 136973027: 136973027
22 KLHL3 NM_017415.2(KLHL3): c.1277C> T (p.Pro426Leu) single nucleotide variant Pathogenic rs387907156 GRCh38 Chromosome 5, 137637338: 137637338
23 KLHL3 NM_017415.2(KLHL3): c.1519G> A (p.Val507Ile) single nucleotide variant Likely pathogenic rs863225302 GRCh38 Chromosome 5, 137628369: 137628369
24 KLHL3 NM_017415.2(KLHL3): c.1519G> A (p.Val507Ile) single nucleotide variant Likely pathogenic rs863225302 GRCh37 Chromosome 5, 136964058: 136964058

Expression for Pseudohypoaldosteronism, Type Iid

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

Pathways for Pseudohypoaldosteronism, Type Iid

GO Terms for Pseudohypoaldosteronism, Type Iid

Sources for Pseudohypoaldosteronism, Type Iid

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
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45 MESH via Orphanet
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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