PHA1B
MCID: PSD114
MIFTS: 60

Pseudohypoaldosteronism, Type I, Autosomal Recessive (PHA1B)

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

Aliases & Classifications for Pseudohypoaldosteronism, Type I, Autosomal Recessive

MalaCards integrated aliases for Pseudohypoaldosteronism, Type I, Autosomal Recessive:

Name: Pseudohypoaldosteronism, Type I, Autosomal Recessive 57 70
Autosomal Recessive Pseudohypoaldosteronism Type 1 12 20 58 29 6 15
Pha1b 57 12 20 72
Pseudohypoaldosteronism, Type I 57 13 70
Pseudohypoaldosteronism Type 1 43 58 29
Pseudohypoaldosteronism Type 1 Autosomal Recessive 20 39
Generalized Pseudohypoaldosteronism Type 1 20 58
Pseudohypoaldosteronism 44 70
Pseudohypoaldosteronism Type I, Autosomal Recessive 72
Pseudohypoaldosteronism 1, Autosomal Recessive 72
Pseudohypoaldosteronism Type 1, Recessive 20
Multisystem Pseudohypoaldosteronism 72
Pha Type I, Autosomal Recessive 72
Pseudohypoaldosteronism Type I 43
Pha I, Autosomal Recessive 57
Autosomal Recessive Pha 1 12
Generalized Pha1 20
Pha Type 1 58
Pha1 43

Characteristics:

Orphanet epidemiological data:

58
generalized pseudohypoaldosteronism type 1
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;
pseudohypoaldosteronism type 1
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
favorable response to sodium chloride treatment
may be lethal in the neonatal period


HPO:

31
pseudohypoaldosteronism, type i, autosomal recessive:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare renal diseases


Summaries for Pseudohypoaldosteronism, Type I, Autosomal Recessive

MedlinePlus Genetics : 43 Pseudohypoaldosteronism type 1 (PHA1) is a condition characterized by problems regulating the amount of sodium in the body. Sodium regulation, which is important for blood pressure and fluid balance, primarily occurs in the kidneys. However, sodium can also be removed from the body through other tissues, such as the sweat glands and colon. Pseudohypoaldosteronism type 1 is named for its characteristic signs and symptoms, which mimic (pseudo) low levels (hypo) of a hormone called aldosterone that helps regulate sodium levels. However, people with PHA1 have high levels of aldosterone.There are two types of PHA1 distinguished by their severity, the genes involved, and how they are inherited. One type, called autosomal dominant PHA1 (also known as renal PHA1) is characterized by excessive sodium loss from the kidneys. This form of the condition is relatively mild and often improves in early childhood. The other type, called autosomal recessive PHA1 (also known as generalized or systemic PHA1) is characterized by sodium loss from the kidneys and other organs, including the sweat glands, salivary glands, and colon. This type of PHA1 is more severe and does not improve with age.The earliest signs of both types of PHA1 are usually the inability to gain weight and grow at the expected rate (failure to thrive) and dehydration, which are typically seen in infants. The characteristic features of both types of PHA1 are excessive amounts of sodium released in the urine (salt wasting), which leads to low levels of sodium in the blood (hyponatremia), and high levels of potassium in the blood (hyperkalemia). Infants with PHA1 can also have high levels of acid in the blood (metabolic acidosis). Hyponatremia, hyperkalemia, or metabolic acidosis can cause nonspecific symptoms such as nausea, vomiting, extreme tiredness (fatigue), and muscle weakness in infants with PHA1.Infants with autosomal recessive PHA1 can have additional signs and symptoms due to the involvement of multiple organs. Affected individuals may experience episodes of abnormal heartbeat (cardiac arrhythmia) or shock because of the imbalance of salts in the body. They may also have recurrent lung infections or lesions on the skin. Although adults with autosomal recessive PHA1 can have repeated episodes of salt wasting, they do not usually have other signs and symptoms of the condition.

MalaCards based summary : Pseudohypoaldosteronism, Type I, Autosomal Recessive, also known as autosomal recessive pseudohypoaldosteronism type 1, is related to arthrogryposis, distal, type 3 and pseudohypoaldosteronism, type i, autosomal dominant, and has symptoms including vomiting and diarrhea. An important gene associated with Pseudohypoaldosteronism, Type I, Autosomal Recessive is SCNN1A (Sodium Channel Epithelial 1 Subunit Alpha), and among its related pathways/superpathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and G-Beta Gamma Signaling. The drugs Enalapril and Enalaprilat have been mentioned in the context of this disorder. Affiliated tissues include colon, kidney and bone, and related phenotypes are hyponatremia and hyperkalemia

Disease Ontology : 12 A pseudohypoaldosteronism characterized by enal salt wasting and high concentrations of sodium in sweat, stool, and saliva that has material basis in homozygous or compound heterozygous mutation in any one of 3 genes encoding subunits of the epithelial sodium channel (ENaC): SCNN1A, SCNN1B, or SCNN1G.

GARD : 20 Autosomal recessive pseudohypoaldosteronism type 1 is a disorder of electrolyte metabolism characterized by excess loss of salt in the urine and high concentrations of sodium in sweat, stool, and saliva. The disorder involves multiple organ systems and is especially dangerous in the newborn period. Laboratory tests may show hyponatremia, hyperkalemia, and increased plasma renin activity with high levels of aldosterone in the blood. Respiratory tract infections are common in affected children. Treatment involves aggressive salt replacement and control of hyperkalemia. The disorder may become less severe with age. Autosomal recessive pseudohypoaldosteronism type 1 (PHA1B) is transmitted in an autosomal recessive manner and is caused by mutations in the genes coding for the subunits of the amiloride-sensitive sodium channel ( SCNN1A, SCNN1B and SCNN1G ).

OMIM® : 57 Autosomal recessive pseudohypoaldosteronism type I is characterized by renal salt wasting and high concentrations of sodium in sweat, stool, and saliva. The disorder involves multiple organ systems and is especially threatening in the neonatal period. Laboratory evaluation shows hyponatremia, hyperkalemia, and increased plasma renin activity with high serum aldosterone concentrations. Respiratory tract infections are common in affected children and may be mistaken for cystic fibrosis (CF; 219700). Aggressive salt replacement and control of hyperkalemia results in survival, and the disorder appears to become less severe with age (review by Scheinman et al., 1999). A milder, autosomal dominant form of type I pseudohypoaldosteronism (PHA1A; 177735) is caused by mutations in the mineralocorticoid receptor gene (MCR, NR3C2; 600983). Gitelman syndrome (263800), another example of primary renal tubular salt wasting, is due to mutation in the thiazide-sensitive sodium-chloride cotransporter (SLC12A3; 600968). Hanukoglu and Hanukoglu (2016) provided a detailed review of the ENaC gene family, including structure, function, tissue distribution, and associated inherited diseases. (264350) (Updated 20-May-2021)

UniProtKB/Swiss-Prot : 72 Pseudohypoaldosteronism 1, autosomal recessive: A rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1B is a severe form involving multiple organ systems, and characterized by an often fulminant presentation in the neonatal period with dehydration, hyponatremia, hyperkalemia, metabolic acidosis, failure to thrive and weight loss.

Related Diseases for Pseudohypoaldosteronism, Type I, Autosomal Recessive

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 I, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 112)
# Related Disease Score Top Affiliating Genes
1 arthrogryposis, distal, type 3 31.5 REN NR3C2 KCNJ1 CUL3
2 pseudohypoaldosteronism, type i, autosomal dominant 30.9 SLC26A11 SCNN1G SCNN1B SCNN1A REN NR3C2
3 miliaria rubra 30.8 SCNN1G SCNN1B SCNN1A
4 miliaria 30.8 SCNN1G SCNN1B SCNN1A
5 metabolic acidosis 30.6 SCNN1G SCNN1B SCNN1A CUL3 ATP6V1B1
6 hypertension, essential 30.5 SCNN1G SCNN1B SCNN1A REN NR3C2 NEDD4L
7 lipoid congenital adrenal hyperplasia 30.4 REN MC2R HSD3B2 CYP11B1
8 renal tubular acidosis 30.4 SCNN1G REN NR3C2 ATP6V1B1
9 pseudohypoaldosteronism 30.3 SCNN1G SCNN1B SCNN1A REN NR3C2 KCNJ1
10 pseudohyperkalemia, familial, 2, due to red cell leak 30.3 SCNN1G REN NR3C2 KCNJ1
11 idiopathic bronchiectasis 30.2 SCNN1G SCNN1B SCNN1A
12 familial hypertension 30.0 REN NR3C2 CUL3
13 corticosterone methyloxidase type i deficiency 29.6 SCNN1G REN HSD3B2 CYP11B1
14 apparent mineralocorticoid excess 29.4 REN NR3C2 KCNJ1 CYP11B1
15 hypokalemia 29.4 REN NR3C2 KCNJ1 CYP11B1
16 bartter disease 29.3 SCNN1G SCNN1B SCNN1A REN NR3C2 KCNJ1
17 liddle syndrome 1 28.8 SCNN1G SCNN1B SCNN1A REN NR3C2 NEDD4L
18 pseudohypoaldosteronism, type iie 11.7
19 pseudohypoaldosteronism, type iid 11.5
20 pseudohypoaldosteronism, type iib 11.5
21 pseudohypoaldosteronism, type iic 11.5
22 pseudohypoaldosteronism, type iia 11.5
23 transient pseudohypoaldosteronism 11.2
24 urinary tract infection 10.5
25 urinary tract obstruction 10.4
26 hydronephrosis 10.2
27 pyelonephritis 10.2
28 acute cystitis 10.2
29 hypoaldosteronism 10.2
30 bronchiectasis 10.2 SCNN1G SCNN1B SCNN1A
31 hypertensive retinopathy 10.2 REN NR3C2
32 left bundle branch hemiblock 10.1 REN NR3C2
33 pure autonomic failure 10.1 REN NEDD4L
34 vesicoureteral reflux 1 10.1
35 bartter syndrome, type 2, antenatal 10.1 SCNN1G SCNN1B SCNN1A KCNJ1
36 anuria 10.1 REN NR3C2
37 antenatal bartter syndrome 10.1 REN KCNJ1
38 cystic fibrosis 10.1
39 mineral metabolism disease 10.1 REN NR3C2 KCNJ1
40 hypoadrenocorticism, familial 10.0 REN MC2R HSD3B2
41 hypertension, early-onset, autosomal dominant, with severe exacerbation in pregnancy 10.0
42 exanthem 10.0
43 autosomal recessive disease 10.0
44 cardiac arrest 10.0
45 acute pyelonephritis 10.0
46 posterior urethral valves 10.0
47 frozen shoulder 10.0 ASIC2 ASIC1
48 endocrine organ benign neoplasm 10.0 REN NR3C2 CYP11B1
49 adrenal rest tumor 9.9 MC2R HSD3B2 CYP11B1
50 adrenal cortical adenoma 9.9 REN MC2R CYP11B1

Graphical network of the top 20 diseases related to Pseudohypoaldosteronism, Type I, Autosomal Recessive:



Diseases related to Pseudohypoaldosteronism, Type I, Autosomal Recessive

Symptoms & Phenotypes for Pseudohypoaldosteronism, Type I, Autosomal Recessive

Human phenotypes related to Pseudohypoaldosteronism, Type I, Autosomal Recessive:

58 31 (show all 31)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hyponatremia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002902
2 hyperkalemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002153
3 metabolic acidosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0001942
4 abnormal circulating aldosterone 58 31 hallmark (90%) Very frequent (99-80%) HP:0040085
5 increased circulating renin level 58 31 hallmark (90%) Very frequent (99-80%) HP:0000848
6 glucocortocoid-insensitive primary hyperaldosteronism 58 31 hallmark (90%) Very frequent (99-80%) HP:0011740
7 dehydration 58 31 frequent (33%) Frequent (79-30%) HP:0001944
8 vomiting 58 31 frequent (33%) Frequent (79-30%) HP:0002013
9 failure to thrive in infancy 58 31 frequent (33%) Frequent (79-30%) HP:0001531
10 hypovolemic shock 58 31 frequent (33%) Frequent (79-30%) HP:0031274
11 recurrent upper and lower respiratory tract infections 58 31 frequent (33%) Frequent (79-30%) HP:0200117
12 feeding difficulties in infancy 58 31 occasional (7.5%) Occasional (29-5%) HP:0008872
13 cholelithiasis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001081
14 arrhythmia 58 31 occasional (7.5%) Occasional (29-5%) HP:0011675
15 cough 58 31 occasional (7.5%) Occasional (29-5%) HP:0012735
16 weight loss 58 31 occasional (7.5%) Occasional (29-5%) HP:0001824
17 osteomyelitis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002754
18 pustule 58 31 occasional (7.5%) Occasional (29-5%) HP:0200039
19 proportionate short stature 58 31 occasional (7.5%) Occasional (29-5%) HP:0003508
20 atopic dermatitis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001047
21 wheezing 58 31 occasional (7.5%) Occasional (29-5%) HP:0030828
22 recurrent tonsillitis 31 occasional (7.5%) HP:0011110
23 failure to thrive 31 HP:0001508
24 hypotension 31 HP:0002615
25 recurrent respiratory infections 31 HP:0002205
26 hyperaldosteronism 31 HP:0000859
27 diarrhea 31 HP:0002014
28 tonsillitis 58 Occasional (29-5%)
29 renal salt wasting 31 HP:0000127
30 hyperactive renin-angiotensin system 31 HP:0000841
31 pseudohypoaldosteronism 31 HP:0008242

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Growth Other:
failure to thrive

Metabolic Features:
dehydration
metabolic acidosis

Laboratory Abnormalities:
hyponatremia
hyperkalemia
increased serum aldosterone
increased plasma renin activity
markedly elevated sodium in urine, sweat, saliva, and stool

Respiratory:
recurrent respiratory infections

Abdomen Gastrointestinal:
vomiting
diarrhea
poor feeding

Genitourinary Kidneys:
renal salt wasting

Clinical features from OMIM®:

264350 (Updated 20-May-2021)

UMLS symptoms related to Pseudohypoaldosteronism, Type I, Autosomal Recessive:


vomiting; diarrhea

GenomeRNAi Phenotypes related to Pseudohypoaldosteronism, Type I, Autosomal Recessive according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00106-A-0 9.75 CACNA1B DHCR7
2 Decreased viability GR00221-A-1 9.75 NEDD4L
3 Decreased viability GR00221-A-2 9.75 NEDD4L
4 Decreased viability GR00221-A-3 9.75 NEDD4L
5 Decreased viability GR00240-S-1 9.75 CYP11B1
6 Decreased viability GR00249-S 9.75 ASIC1 ASIC2 ASIC5 CUL3 DHCR7 KCNJ1
7 Decreased viability GR00381-A-1 9.75 CACNA1B DHCR7 RHBG
8 Decreased viability GR00386-A-1 9.75 ASIC1 HSD3B2 NR3C2 SCNN1G SLC26A11
9 Decreased viability GR00402-S-2 9.75 ASIC1 DHCR7 MC2R RHBG

MGI Mouse Phenotypes related to Pseudohypoaldosteronism, Type I, Autosomal Recessive:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.31 ASIC1 ASIC2 ATP6V1B1 CACNA1B CUL3 CYP11B1
2 cardiovascular system MP:0005385 10.21 ASIC1 ASIC2 ATP6V1B1 CACNA1B CUL3 CYP11B1
3 homeostasis/metabolism MP:0005376 10.19 ASIC5 ATP6V1B1 CACNA1B CUL3 CYP11B1 DHCR7
4 growth/size/body region MP:0005378 10.13 ASIC5 ATP6V1B1 CACNA1B CUL3 CYP11B1 DHCR7
5 muscle MP:0005369 9.76 ASIC2 CUL3 CYP11B1 DHCR7 NEDD4L NR3C2
6 nervous system MP:0003631 9.73 ASIC1 ASIC2 ATP6V1B1 CACNA1B CUL3 DHCR7
7 renal/urinary system MP:0005367 9.44 ASIC2 ATP6V1B1 CYP11B1 DHCR7 KCNJ1 NEDD4L

Drugs & Therapeutics for Pseudohypoaldosteronism, Type I, Autosomal Recessive

Drugs for Pseudohypoaldosteronism, Type I, Autosomal Recessive (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Enalapril Approved, Vet_approved Phase 2 75847-73-3 5362032 40466924
2
Enalaprilat Approved Phase 2 76420-72-9 6917719
3
protease inhibitors Phase 2
4 Chelating Agents Phase 2
5 Polystyrene sulfonic acid Phase 2
6 Angiotensin-Converting Enzyme Inhibitors Phase 2
7 Antihypertensive Agents Phase 2
8 HIV Protease Inhibitors Phase 2
9 Mineralocorticoids

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Phase II Study of the Pathophysiology and Treatment With Enalapril and Polystyrene Sulfonate for Pseudohypoaldosteronism, Type I Completed NCT00004328 Phase 2 enalapril;polystyrene sulfonate
2 Cardiovascular Evaluation of a Rare Condition With Hyperaldosteronism Without Hypertension: PHA 1 Completed NCT00646828
3 Rare Genetic Disorders of the Airways: Cross-sectional Comparison of Clinical Features, and Development of Novel Screening and Genetic Tests Completed NCT00323167
4 Genetic Disorders of Mucociliary Clearance Completed NCT00368446

Search NIH Clinical Center for Pseudohypoaldosteronism, Type I, Autosomal Recessive

Cochrane evidence based reviews: pseudohypoaldosteronism

Genetic Tests for Pseudohypoaldosteronism, Type I, Autosomal Recessive

Genetic tests related to Pseudohypoaldosteronism, Type I, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Autosomal Recessive Pseudohypoaldosteronism Type 1 29 SCNN1A SCNN1B SCNN1G
2 Pseudohypoaldosteronism Type 1 29

Anatomical Context for Pseudohypoaldosteronism, Type I, Autosomal Recessive

MalaCards organs/tissues related to Pseudohypoaldosteronism, Type I, Autosomal Recessive:

40
Colon, Kidney, Bone, Cortex, Adrenal Gland, Adrenal Cortex

Publications for Pseudohypoaldosteronism, Type I, Autosomal Recessive

Articles related to Pseudohypoaldosteronism, Type I, Autosomal Recessive:

(show all 42)
# Title Authors PMID Year
1
A novel splice-site mutation in the gamma subunit of the epithelial sodium channel gene in three pseudohypoaldosteronism type 1 families. 57 6
8640238 1996
2
Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. 57 6
8589714 1996
3
Lung symptoms in pseudohypoaldosteronism type 1 are associated with deficiency of the alpha-subunit of the epithelial sodium channel. 61 6
10586178 1999
4
Exclusion of the locus for autosomal recessive pseudohypoaldosteronism type 1 from the mineralocorticoid receptor gene region on human chromosome 4q by linkage analysis. 57 61
7593448 1995
5
A novel mutation in the human mineralocorticoid receptor gene in a Japanese family with autosomal-dominant pseudohypoaldosteronism type 1. 6
27780983 2016
6
Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases. 57
26772908 2016
7
[Pseudohypoaldosteronisme type I: a rare cause of failure to thrive]. 6
22463955 2012
8
Clinical and molecular features of type 1 pseudohypoaldosteronism. 6
19571553 2009
9
Elucidating the underlying molecular pathogenesis of NR3C2 mutants causing autosomal dominant pseudohypoaldosteronism type 1. 6
16954160 2006
10
Recurrence of the R947X mutation in unrelated families with autosomal dominant pseudohypoaldosteronism type 1: evidence for a mutational hot spot in the mineralocorticoid receptor gene. 6
16757525 2006
11
Autosomal dominant pseudohypoaldosteronism type 1: mechanisms, evidence for neonatal lethality, and phenotypic expression in adults. 6
16611713 2006
12
Autosomal-dominant pseudohypoaldosteronism type 1 in a Turkish family is associated with a novel nonsense mutation in the human mineralocorticoid receptor gene. 6
15126534 2004
13
A novel nonsense mutation of the mineralocorticoid receptor gene in a Swedish family with pseudohypoaldosteronism type I (PHA1). 6
14715854 2004
14
Different inactivating mutations of the mineralocorticoid receptor in fourteen families affected by type I pseudohypoaldosteronism. 6
12788847 2003
15
Identification of a novel mutation in the human mineralocorticoid receptor gene in a german family with autosomal-dominant pseudohypoaldosteronism type 1: further evidence for marked interindividual clinical heterogeneity. 6
12679457 2003
16
Evidence for genetic heterogeneity of pseudohypoaldosteronism type 1: identification of a novel mutation in the human mineralocorticoid receptor in one sporadic case and no mutations in two autosomal dominant kindreds. 6
11344206 2001
17
Compound heterozygous mutations in the gamma subunit gene of ENaC (1627delG and 1570-1G-->A) in one sporadic Japanese patient with a systemic form of pseudohypoaldosteronism type 1. 6
11231969 2001
18
A novel missense mutation of mineralocorticoid receptor gene in one Japanese family with a renal form of pseudohypoaldosteronism type 1. 6
11134129 2000
19
Functional expression of a pseudohypoaldosteronism type I mutated epithelial Na+ channel lacking the pore-forming region of its alpha subunit. 6
10510337 1999
20
Polymorphisms of amiloride-sensitive sodium channel subunits in five sporadic cases of pseudohypoaldosteronism: do they have pathologic potential? 57
10404817 1999
21
Genetic disorders of renal electrolyte transport. 57
10202170 1999
22
Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I. 6
9662404 1998
23
A mutation causing pseudohypoaldosteronism type 1 identifies a conserved glycine that is involved in the gating of the epithelial sodium channel. 6
9118951 1997
24
Localisation of pseudohypoaldosteronism genes to chromosome 16p12.2-13.11 and 12p13.1-pter by homozygosity mapping. 57
8824886 1996
25
Pseudohypoaldosteronism with increased sweat and saliva electrolyte values and frequent lower respiratory tract infections mimicking cystic fibrosis. 57
7965429 1994
26
Type I pseudohypoaldosteronism includes two clinically and genetically distinct entities with either renal or multiple target organ defects. 57
1939532 1991
27
Pseudohypoaldosteronism in eight families: different forms of inheritance are evidence for various genetic defects. 57
2137831 1990
28
Aldosterone-receptor deficiency in pseudohypoaldosteronism. 57
2932642 1985
29
The natural history of salt-wasting disorders of adrenal and renal origin. 57
6384251 1984
30
Pseudohypoaldosteronism. 57
7002056 1980
31
Pseudohypoaldosteronism: multiple target organ unresponsiveness to mineralocorticoid hormones. 57
218983 1979
32
[Pseudo-hypoaldosteronism in infants. Apropos of 4 cases, 2 concerning brothers]. 57
643461 1978
33
[Autosomal recessive transmission of familial pseudohypoaldosteronism]. 57
606192 1977
34
[Familial pseudohypoaldosteronism (apropos of 5 cases)]. 57
851368 1977
35
[Aldosterone secretion rate and plasma renin activity in a case of pseudo-hypoaldosteronism]. 57
5433048 1970
36
[PSEUDO-HYPOALDOSTERONISM]. 57
14103260 1963
37
[Saline diabetes caused by congenital insensitivity of the tubule to aldosterone: "pseudo-hypoadrenocorticism"]. 57
13760685 1960
38
Reducing ╬▒ENaC expression in the kidney connecting tubule induces pseudohypoaldosteronism type 1 symptoms during K+ loading. 61
26582762 2016
39
Pseudohypoaldosteronism type 1 due to novel variants of SCNN1B gene. 61
26807262 2016
40
Five novel mutations in the SCNN1A gene causing autosomal recessive pseudohypoaldosteronism type 1. 61
23416952 2013
41
Case report: severe neonatal hyperkalemia due to pseudohypoaldosteronism type 1. 61
19657313 2009
42
Disorders of the epithelial Na(+) channel in Liddle's syndrome and autosomal recessive pseudohypoaldosteronism type 1. 61
11014928 2000

Variations for Pseudohypoaldosteronism, Type I, Autosomal Recessive

ClinVar genetic disease variations for Pseudohypoaldosteronism, Type I, Autosomal Recessive:

6 (show top 50) (show all 554)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NR3C2 NR3C2, 1-BP DEL, 1226G Deletion Pathogenic 8553 GRCh37:
GRCh38:
2 NR3C2 NR3C2, 1-BP DEL, 1597T Deletion Pathogenic 8554 GRCh37:
GRCh38:
3 NR3C2 NM_000901.5(NR3C2):c.1609C>T (p.Arg537Ter) SNV Pathogenic 8555 rs121912562 GRCh37: 4:149356404-149356404
GRCh38: 4:148435252-148435252
4 NR3C2 NM_000901.5(NR3C2):c.2365+3del Deletion Pathogenic 8556 rs1560949756 GRCh37: 4:149075699-149075699
GRCh38: 4:148154548-148154548
5 NR3C2 NM_000901.5(NR3C2):c.2871dup (p.Ala958fs) Duplication Pathogenic 8558 rs1560910156 GRCh37: 4:149002578-149002579
GRCh38: 4:148081427-148081428
6 NR3C2 NM_000901.5(NR3C2):c.2771T>C (p.Leu924Pro) SNV Pathogenic 8559 rs121912563 GRCh37: 4:149035283-149035283
GRCh38: 4:148114132-148114132
7 NR3C2 NM_000901.5(NR3C2):c.1131dup (p.Glu378Ter) Duplication Pathogenic 8560 rs1560735659 GRCh37: 4:149356881-149356882
GRCh38: 4:148435729-148435730
8 NR3C2 NR3C2, 8-BP DEL, NT537 Deletion Pathogenic 8561 GRCh37:
GRCh38:
9 NR3C2 NM_000901.5(NR3C2):c.1935C>A (p.Cys645Ter) SNV Pathogenic 8562 rs121912564 GRCh37: 4:149115976-149115976
GRCh38: 4:148194825-148194825
10 NR3C2 NM_000901.5(NR3C2):c.2327A>G (p.Gln776Arg) SNV Pathogenic 8563 rs121912565 GRCh37: 4:149075740-149075740
GRCh38: 4:148154589-148154589
11 NR3C2 NM_000901.5(NR3C2):c.1897G>A (p.Gly633Arg) SNV Pathogenic 8564 rs121912566 GRCh37: 4:149181130-149181130
GRCh38: 4:148259978-148259978
12 NR3C2 NM_000901.5(NR3C2):c.2936T>C (p.Leu979Pro) SNV Pathogenic 8565 rs121912567 GRCh37: 4:149002514-149002514
GRCh38: 4:148081363-148081363
13 NR3C2 NM_000901.5(NR3C2):c.488C>G (p.Ser163Ter) SNV Pathogenic 8566 rs121912568 GRCh37: 4:149357525-149357525
GRCh38: 4:148436373-148436373
14 NR3C2 NM_000901.5(NR3C2):c.2839C>T (p.Arg947Ter) SNV Pathogenic 8567 rs121912569 GRCh37: 4:149002611-149002611
GRCh38: 4:148081460-148081460
15 NR3C2 NM_000901.5(NR3C2):c.1308T>A (p.Cys436Ter) SNV Pathogenic 8568 rs121912570 GRCh37: 4:149356705-149356705
GRCh38: 4:148435553-148435553
16 NR3C2 NM_000901.5(NR3C2):c.2024C>G (p.Ser675Ter) SNV Pathogenic 8570 rs121912572 GRCh37: 4:149076043-149076043
GRCh38: 4:148154892-148154892
17 NR3C2 NM_000901.5(NR3C2):c.2453C>T (p.Ser818Leu) SNV Pathogenic 8571 rs121912573 GRCh37: 4:149073677-149073677
GRCh38: 4:148152526-148152526
18 NR3C2 NM_000901.5(NR3C2):c.2915A>G (p.Glu972Gly) SNV Pathogenic 8572 rs121912574 GRCh37: 4:149002535-149002535
GRCh38: 4:148081384-148081384
19 SCNN1G NM_001039.4(SCNN1G):c.1570-1G>A SNV Pathogenic 8825 rs1596779402 GRCh37: 16:23226409-23226409
GRCh38: 16:23215088-23215088
20 SCNN1G NM_001039.4(SCNN1G):c.318-1G>A SNV Pathogenic 8826 rs1567262640 GRCh37: 16:23200691-23200691
GRCh38: 16:23189370-23189370
21 SCNN1G NM_001039.4(SCNN1G):c.1627del (p.Val543fs) Deletion Pathogenic 8827 rs1596779433 GRCh37: 16:23226467-23226467
GRCh38: 16:23215146-23215146
22 SCNN1A NM_001038.6(SCNN1A):c.203_204del (p.Ile68fs) Deletion Pathogenic 9263 rs765835593 GRCh37: 12:6483746-6483747
GRCh38: 12:6374580-6374581
23 SCNN1A NM_001038.6(SCNN1A):c.1522C>T (p.Arg508Ter) SNV Pathogenic 9264 rs137852634 GRCh37: 12:6458147-6458147
GRCh38: 12:6348981-6348981
24 SCNN1A NM_001038.6(SCNN1A):c.1449del (p.Tyr484fs) Deletion Pathogenic 9265 rs756434927 GRCh37: 12:6458378-6458378
GRCh38: 12:6349212-6349212
25 SCNN1A NM_001038.6(SCNN1A):c.729del (p.Val245fs) Deletion Pathogenic 9266 rs1592074026 GRCh37: 12:6471363-6471363
GRCh38: 12:6362197-6362197
26 SCNN1A NM_001038.6(SCNN1A):c.1685C>T (p.Ser562Leu) SNV Pathogenic 9267 rs137852635 GRCh37: 12:6457364-6457364
GRCh38: 12:6348198-6348198
27 SCNN1A NM_001038.6(SCNN1A):c.1439+1G>A SNV Pathogenic 802813 rs1369791519 GRCh37: 12:6458492-6458492
GRCh38: 12:6349326-6349326
28 SCNN1A NM_001038.6(SCNN1A):c.1221_1227dup (p.Lys410fs) Duplication Pathogenic 802814 rs1565478701 GRCh37: 12:6463930-6463931
GRCh38: 12:6354764-6354765
29 SCNN1A NM_001038.6(SCNN1A):c.1361-2A>G SNV Pathogenic 992425 GRCh37: 12:6458573-6458573
GRCh38: 12:6349407-6349407
30 NR3C2 NM_000901.5(NR3C2):c.1951C>T (p.Arg651Ter) SNV Pathogenic 430357 rs1131691921 GRCh37: 4:149115960-149115960
GRCh38: 4:148194809-148194809
31 NR3C2 NM_000901.5(NR3C2):c.2755C>T (p.Gln919Ter) SNV Likely pathogenic 623200 rs1553986377 GRCh37: 4:149035299-149035299
GRCh38: 4:148114148-148114148
32 NR3C2 NM_000901.5(NR3C2):c.2657T>G (p.Leu886Arg) SNV Likely pathogenic 623478 rs1560928649 GRCh37: 4:149035397-149035397
GRCh38: 4:148114246-148114246
33 CUL3 NM_003590.5(CUL3):c.173A>G (p.Tyr58Cys) SNV Likely pathogenic 559557 rs1553535841 GRCh37: 2:225422467-225422467
GRCh38: 2:224557750-224557750
34 SCNN1G NM_001039.4(SCNN1G):c.142dup (p.Arg48fs) Duplication Likely pathogenic 804476 rs1596760831 GRCh37: 16:23197731-23197732
GRCh38: 16:23186410-23186411
35 SCNN1B NM_000336.3(SCNN1B):c.1074C>A (p.Tyr358Ter) SNV Likely pathogenic 488409 rs1182475940 GRCh37: 16:23383126-23383126
GRCh38: 16:23371805-23371805
36 NR3C2 NM_000901.5(NR3C2):c.2096del (p.Pro699fs) Deletion Likely pathogenic 522499 rs748573472 GRCh37: 4:149075971-149075971
GRCh38: 4:148154820-148154820
37 NR3C2 NM_000901.5(NR3C2):c.2017C>T (p.Arg673Ter) SNV Likely pathogenic 8569 rs121912571 GRCh37: 4:149076050-149076050
GRCh38: 4:148154899-148154899
38 SCNN1B NM_000336.3(SCNN1B):c.109G>A (p.Gly37Ser) SNV Uncertain significance 8832 rs137852706 GRCh37: 16:23360029-23360029
GRCh38: 16:23348708-23348708
39 CUL3 NM_003590.5(CUL3):c.310A>T (p.Thr104Ser) SNV Uncertain significance 334634 rs886055696 GRCh37: 2:225400313-225400313
GRCh38: 2:224535596-224535596
40 KLHL3 NM_017415.3(KLHL3):c.*2448C>T SNV Uncertain significance 350949 rs886059945 GRCh37: 5:136955339-136955339
GRCh38: 5:137619650-137619650
41 SCNN1A NM_001038.6(SCNN1A):c.*914A>G SNV Uncertain significance 310119 rs62619209 GRCh37: 12:6456125-6456125
GRCh38: 12:6346959-6346959
42 SCNN1A NM_001038.6(SCNN1A):c.876-13C>T SNV Uncertain significance 310146 rs201235216 GRCh37: 12:6465059-6465059
GRCh38: 12:6355893-6355893
43 KLHL3 NM_017415.3(KLHL3):c.-402C>T SNV Uncertain significance 351004 rs774532097 GRCh37: 5:137071737-137071737
GRCh38: 5:137736048-137736048
44 SCNN1A NM_001038.6(SCNN1A):c.*113C>T SNV Uncertain significance 310128 rs62620999 GRCh37: 12:6456926-6456926
GRCh38: 12:6347760-6347760
45 CUL3 NM_003590.5(CUL3):c.*2854A>G SNV Uncertain significance 334591 rs772430576 GRCh37: 2:225336108-225336108
GRCh38: 2:224471391-224471391
46 SCNN1A NM_001038.6(SCNN1A):c.319G>A (p.Gly107Arg) SNV Uncertain significance 310152 rs144763378 GRCh37: 12:6483631-6483631
GRCh38: 12:6374465-6374465
47 SCNN1B NM_000336.3(SCNN1B):c.1713C>T (p.Tyr571=) SNV Uncertain significance 318443 rs758251652 GRCh37: 16:23391912-23391912
GRCh38: 16:23380591-23380591
48 KLHL3 NM_017415.3(KLHL3):c.*1034C>T SNV Uncertain significance 350969 rs886059951 GRCh37: 5:136956753-136956753
GRCh38: 5:137621064-137621064
49 CUL3 NM_003590.5(CUL3):c.*1518A>T SNV Uncertain significance 334611 rs886055690 GRCh37: 2:225337444-225337444
GRCh38: 2:224472727-224472727
50 NR3C2 NM_000901.5(NR3C2):c.-111C>T SNV Uncertain significance 347742 rs886059132 GRCh37: 4:149363420-149363420
GRCh38: 4:148442268-148442268

UniProtKB/Swiss-Prot genetic disease variations for Pseudohypoaldosteronism, Type I, Autosomal Recessive:

72
# Symbol AA change Variation ID SNP ID
1 SCNN1A p.Ser562Leu VAR_015834 rs137852635
2 SCNN1A p.Gly327Cys VAR_026518 rs974854786
3 SCNN1B p.Gly37Ser VAR_007127 rs137852706

Expression for Pseudohypoaldosteronism, Type I, Autosomal Recessive

Search GEO for disease gene expression data for Pseudohypoaldosteronism, Type I, Autosomal Recessive.

Pathways for Pseudohypoaldosteronism, Type I, Autosomal Recessive

Pathways related to Pseudohypoaldosteronism, Type I, Autosomal Recessive according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.13 TRPV4 SLC26A11 SCNN1G SCNN1B SCNN1A RHBG
2
Show member pathways
12.34 SCNN1G SCNN1B SCNN1A CACNA1B
3
Show member pathways
12.1 TRPV4 SCNN1G SCNN1B SCNN1A NEDD4L ATP6V1B1
4
Show member pathways
12.01 TRPV4 ASIC5 ASIC2 ASIC1
5
Show member pathways
11.77 SCNN1G SCNN1B SCNN1A ASIC2
6 11.12 SCNN1G SCNN1B SCNN1A
7 11.02 SCNN1G SCNN1B SCNN1A NEDD4L KCNJ1
8 10.67 SCNN1G SCNN1B SCNN1A NR3C2 NEDD4L KCNJ1
9 10.61 SCNN1G SCNN1B SCNN1A

GO Terms for Pseudohypoaldosteronism, Type I, Autosomal Recessive

Cellular components related to Pseudohypoaldosteronism, Type I, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of membrane GO:0016021 10.17 TRPV4 SLC26A11 SCNN1G SCNN1B SCNN1A RHBG
2 plasma membrane GO:0005886 10.13 TRPV4 SLC26A11 SCNN1G SCNN1B SCNN1A RHBG
3 apical plasma membrane GO:0016324 9.77 TRPV4 SCNN1G SCNN1B SCNN1A ATP6V1B1
4 integral component of plasma membrane GO:0005887 9.65 TRPV4 SLC26A11 SCNN1G SCNN1B SCNN1A RHBG
5 membrane GO:0016020 9.6 TRPV4 SLC26A11 SCNN1G SCNN1B SCNN1A RHBG
6 plasma membrane protein complex GO:0098797 9.4 SCNN1G SCNN1B
7 sodium channel complex GO:0034706 9.33 SCNN1G SCNN1B SCNN1A

Biological processes related to Pseudohypoaldosteronism, Type I, Autosomal Recessive according to GeneCards Suite gene sharing:

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 sodium ion transmembrane transport GO:0035725 9.8 SCNN1G SCNN1B SCNN1A ASIC5 ASIC2 ASIC1
2 calcium ion transport GO:0006816 9.76 TRPV4 CACNA1B ASIC1
3 regulation of ion transmembrane transport GO:0034765 9.76 NEDD4L KCNJ1 CACNA1B ASIC2
4 calcium ion transmembrane transport GO:0070588 9.74 TRPV4 CACNA1B ASIC1
5 regulation of membrane potential GO:0042391 9.73 NEDD4L ASIC2 ASIC1
6 sodium ion transport GO:0006814 9.7 SCNN1G SCNN1B SCNN1A NEDD4L ASIC5 ASIC2
7 ion transport GO:0006811 9.7 TRPV4 SLC26A11 SCNN1G SCNN1B SCNN1A KCNJ1
8 steroid biosynthetic process GO:0006694 9.69 HSD3B2 DHCR7 CYP11B1
9 multicellular organismal water homeostasis GO:0050891 9.67 TRPV4 SCNN1G SCNN1B SCNN1A
10 sensory perception of taste GO:0050909 9.65 SCNN1G SCNN1B SCNN1A
11 excretion GO:0007588 9.65 SCNN1G SCNN1B NEDD4L KCNJ1 ATP6V1B1
12 calcium ion import GO:0070509 9.58 TRPV4 CACNA1B
13 sodium ion homeostasis GO:0055078 9.58 SCNN1G SCNN1B SCNN1A
14 response to acidic pH GO:0010447 9.55 ASIC2 ASIC1
15 monovalent inorganic cation transport GO:0015672 9.54 ASIC2 ASIC1
16 glucocorticoid biosynthetic process GO:0006704 9.52 HSD3B2 CYP11B1
17 sensory perception of sour taste GO:0050915 9.49 ASIC2 ASIC1
18 cellular response to aldosterone GO:1904045 9.43 SCNN1G SCNN1B
19 ion transmembrane transport GO:0034220 9.32 TRPV4 SCNN1G SCNN1B SCNN1A NEDD4L KCNJ1

Molecular functions related to Pseudohypoaldosteronism, Type I, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion channel activity GO:0005216 9.65 TRPV4 SCNN1G CACNA1B ASIC2 ASIC1
2 WW domain binding GO:0050699 9.54 SCNN1G SCNN1B SCNN1A
3 cation channel activity GO:0005261 9.46 TRPV4 CACNA1B ASIC2 ASIC1
4 sodium channel activity GO:0005272 9.43 SCNN1G SCNN1B SCNN1A ASIC5 ASIC2 ASIC1
5 ion gated channel activity GO:0022839 9.32 ASIC2 ASIC1
6 ligand-gated sodium channel activity GO:0015280 9.1 SCNN1G SCNN1B SCNN1A ASIC5 ASIC2 ASIC1

Sources for Pseudohypoaldosteronism, Type I, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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