Pseudohypoaldosteronism, Type Iie malady

Genetic diseases, Rare diseases, Cardiovascular diseases, Nephrological diseases, Fetal diseases categories

Aliases & Classifications for Pseudohypoaldosteronism, Type Iie

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46OMIM, 9diseasecard, 19GeneReviews, 42NIH Rare Diseases, 20GeneTests, 21Genetics Home Reference, 44Novoseek, 48Orphanet, 22GTR, 61UMLS, 34MESH via Orphanet, 26ICD10 via Orphanet, 62UMLS via Orphanet
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Aliases & Descriptions for Pseudohypoaldosteronism, Type Iie:

Name: Pseudohypoaldosteronism, Type Iie 46 9 61
Pseudohypoaldosteronism Type 2 19 42 20 21 48
Gordon Hyperkalemia-Hypertension Syndrome 42 21 48
Gordon Syndrome 42 44 48
Phaii 19 42 48
Pha2 19 42 48
Hyperkaliemia - Hypertension, Gordon Type 42 48
Mineralocorticoid Resistant Hyperkalemia 42 48
Camptodactyly - Cleft Palate- Clubfoot 42 48
Familial Hyperkalemic Hypertension 42 48
Pseudohypoaldosteronism Type Ii 19 21
Pseudohypoaldosteronism Type 2e 48 22
Distal Arthrogryposis Type Iia 42 48
Distal Arthrogryposis Type 3 42 48
Spitzer-Weinstein Syndrome 42 48
Hypertensive Hyperkalemia 42 48
Chloride Shunt Syndrome 42 48
Arthrogryposis Multiplex Congenita, Distal, Type Iia 61
Arthrogryposis Multiplex Congenita Distal Type 2a 42
Hyperpotassemia and Hypertension, Familial 61
Camptodactyly, Cleft Palate, and Clubfoot 42
Hyperpotassemia and Hypertension Familial 42
Familial Hyperpotassemia and Hypertension 21
Familial Hypertensive Hyperkalemia 21
Familial Hyperkalemiahypertension 19
Pseudohypoaldosteronism, Type Iid 61
Pseudohypoaldosteronism, Type Ii 61
Arthrogryposis Distal Type 3 42
Gordon’s Syndrome 19
Pha2e 48
Da3 42


Characteristics (Orphanet epidemiological data):

gordon syndrome:
Inheritance: Autosomal dominant; Age of onset: Antenatal,Neonatal; Age of death: normal life expectancy
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)

External Ids:

OMIM46 614496
Orphanet48 376, 757, 300530
MESH via Orphanet34 C537288
ICD10 via Orphanet26 Q68.8, I15.1
UMLS via Orphanet62 C1449844

Summaries for Pseudohypoaldosteronism, Type Iie

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NIH Rare Diseases:42 Gordon syndrome is a rare, inherited type of distal arthrogryposis typically characterized by a combination of camptodactyly (a permanent fixation of several fingers in a flexed position), clubfoot (abnormal bending inward of the foot), and less frequently, cleft palate. intelligence is usually normal. in some cases, additional abnormalities such as scoliosis or undescended testicles in males may be present. the range and severity of symptoms may vary from case to case. gordon syndrome is thought to be inherited in an autosomal dominant or x-linked dominant manner. the exact cause remains unknown. last updated: 12/5/2012

MalaCards based summary: Pseudohypoaldosteronism, Type Iie, also known as pseudohypoaldosteronism type 2, is related to pseudohypoaldosteronism and pseudohypoaldosteronism, type iia, and has symptoms including talipes, camptodactyly of finger and hypertension. An important gene associated with Pseudohypoaldosteronism, Type Iie is CUL3 (cullin 3), and among its related pathways are Ion channel transport and PI3K / Akt Signaling. The compounds thiazide and chlorine have been mentioned in the context of this disorder. Affiliated tissues include kidney and testes.

Genetics Home Reference:21 Pseudohypoaldosteronism type 2 (PHA2) is a condition characterized by problems regulating 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.

Description from OMIM:46 614496

GeneReviews summary for pha2

Related Diseases for Pseudohypoaldosteronism, Type Iie

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Graphical network of diseases related to Pseudohypoaldosteronism, Type Iie:

Diseases related to pseudohypoaldosteronism, type iie

Symptoms for Pseudohypoaldosteronism, Type Iie

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Symptoms by clinical synopsis from OMIM:


Clinical features from OMIM:



 48 (show all 23)
  • camptodactyly of fingers
  • talipes-varus/metatarsal varus
  • autosomal dominant inheritance
  • high vaulted/narrow palate
  • muscle hypotrophy/atrophy/dystrophy/agenesis/amyotrophy
  • facial structural asymmetry/facial hemiatrophy/facial hemihypertrophy
  • cleft palate without cleft lip/submucosal cleft palate/bifid uvula
  • hearing loss/hypoacusia/deafness
  • pectus excavatum
  • scoliosis
  • syndactyly of fingers/interdigital palm
  • clinodactyly of fifth finger
  • undescended/ectopic testes/cryptorchidia/unfixed testes
  • restricted joint mobility/joint stiffness/ankylosis
  • short stature/dwarfism/nanism
  • chronic arterial hypertension
  • hyperkalemia
  • nausea/vomiting/regurgitation/merycism/hyperemesis
  • contractures/cramps/trismus/tetania/claudication/opisthotonos
  • anomalies of teeth and dentition
  • enamel anomaly
  • muscle weakness/flaccidity
  • failure to thrive/difficulties for feeding in infancy/growth delay

HPO human phenotypes related to Pseudohypoaldosteronism, Type Iie:

(show all 24)
id Description Frequency HPO Source Accession
1 talipes hallmark (90%) HP:0001883
2 camptodactyly of finger hallmark (90%) HP:0100490
3 hypertension hallmark (90%) HP:0000822
4 hyperkalemia hallmark (90%) HP:0002153
5 amyotrophy typical (50%) HP:0003202
6 flexion contracture typical (50%) HP:0001371
7 nausea and vomiting typical (50%) HP:0002017
8 cryptorchidism occasional (7.5%) HP:0000028
9 cleft palate occasional (7.5%) HP:0000175
10 facial asymmetry occasional (7.5%) HP:0000324
11 hearing impairment occasional (7.5%) HP:0000365
12 pectus excavatum occasional (7.5%) HP:0000767
13 limitation of joint mobility occasional (7.5%) HP:0001376
14 scoliosis occasional (7.5%) HP:0002650
15 clinodactyly of the 5th finger occasional (7.5%) HP:0004209
16 short stature occasional (7.5%) HP:0004322
17 finger syndactyly occasional (7.5%) HP:0006101
18 abnormality of dental enamel occasional (7.5%) HP:0000682
19 muscle weakness occasional (7.5%) HP:0001324
20 autosomal dominant inheritance HP:0000006
21 hypertension HP:0000822
22 metabolic acidosis HP:0001942
23 hyperkalemia HP:0002153
24 hyperchloremia HP:0011423

Drugs & Therapeutics for Pseudohypoaldosteronism, Type Iie

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Drug clinical trials:

Search ClinicalTrials for Pseudohypoaldosteronism, Type Iie

Search NIH Clinical Center for Pseudohypoaldosteronism, Type Iie

Genetic Tests for Pseudohypoaldosteronism, Type Iie

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Genetic tests related to Pseudohypoaldosteronism, Type Iie:

id Genetic test Affiliating Genes
1 Pseudohypoaldosteronism Type Ii20 WNK4
2 Pseudohypoaldosteronism Type Iie20 CUL3
3 Pseudohypoaldosteronism Type 2e22
4 Pseudohypoaldosteronism, Type 222

Anatomical Context for Pseudohypoaldosteronism, Type Iie

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MalaCards organs/tissues related to Pseudohypoaldosteronism, Type Iie:

Kidney, Testes

Animal Models for Pseudohypoaldosteronism, Type Iie or affiliated genes

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Publications for Pseudohypoaldosteronism, Type Iie

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Variations for Pseudohypoaldosteronism, Type Iie

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

id Symbol AA change Variation ID SNP ID

Clinvar genetic disease variations for Pseudohypoaldosteronism, Type Iie:

5 (show all 57)
id Gene Variation Type Significance SNP ID Assembly Location
1CUL3NM_003590.4(CUL3): c.1207-12T> Gsingle nucleotide variantPathogenicrs199469651GRCh37Chr 2, 225368551: 225368551
2CUL3NM_003590.4(CUL3): c.1207-1G> Asingle nucleotide variantPathogenicrs199469654GRCh37Chr 2, 225368540: 225368540
3CUL3NM_003590.4(CUL3): c.1207-26A> Gsingle nucleotide variantPathogenicrs199469650GRCh37Chr 2, 225368565: 225368565
4CUL3NM_003590.4(CUL3): c.1207-28T> Gsingle nucleotide variantPathogenicrs199469649GRCh37Chr 2, 225368567: 225368567
5CUL3NM_003590.4(CUL3): c.1207-3C> Tsingle nucleotide variantPathogenicrs199469653GRCh37Chr 2, 225368542: 225368542
6CUL3NM_003590.4(CUL3): c.1207-5T> Asingle nucleotide variantPathogenicrs199469652GRCh37Chr 2, 225368544: 225368544
7CUL3NM_003590.4(CUL3): c.1236G> A (p.Leu412=)single nucleotide variantPathogenicrs199469655GRCh37Chr 2, 225368510: 225368510
8CUL3NM_003590.4(CUL3): c.1376A> G (p.Lys459Arg)single nucleotide variantPathogenicrs199469658GRCh37Chr 2, 225368370: 225368370
9CUL3NM_003590.4: c.1376_1377+4delAGGTAAdeletionPathogenicrs199469657GRCh37Chr 2, 225368365: 225368370
10CUL3NM_003590.4(CUL3): c.1377dupG (p.Thr460Aspfs)duplicationPathogenicrs199469659GRCh37Chr 2, 225368369: 225368370
11CUL3NM_003590.4(CUL3): c.1377+1G> Csingle nucleotide variantPathogenicrs199469660GRCh37Chr 2, 225368368: 225368368
12CUL3NM_003590.4(CUL3): c.1377+3A> Gsingle nucleotide variantPathogenicrs199469661GRCh37Chr 2, 225368366: 225368366
13KLHL3NM_017415.2(KLHL3): c.1410G> A (p.Trp470Ter)single nucleotide variantPathogenicrs199469644GRCh37Chr 5, 136969766: 136969766
14KLHL3NM_017415.2(KLHL3): c.721delC (p.Leu241Phefs)deletionPathogenicrs199469647GRCh37Chr 5, 136997636: 136997636
15KLHL3NM_017415.2(KLHL3): c.753+1G> Asingle nucleotide variantPathogenicrs199469648GRCh37Chr 5, 136997603: 136997603
16KLHL3NM_017415.2(KLHL3): c.1019C> T (p.Ala340Val)single nucleotide variantPathogenicrs199469628GRCh37Chr 5, 136975551: 136975551
17KLHL3NM_017415.2(KLHL3): c.1480G> A (p.Ala494Thr)single nucleotide variantPathogenicrs199469633GRCh37Chr 5, 136964097: 136964097
18KLHL3NM_017415.2(KLHL3): c.230C> A (p.Ala77Glu)single nucleotide variantPathogenicrs199469623GRCh37Chr 5, 137045450: 137045450
19KLHL3NM_017415.2(KLHL3): c.491G> T (p.Cys164Phe)single nucleotide variantPathogenicrs199469626GRCh37Chr 5, 137028009: 137028009
20KLHL3NM_017415.2(KLHL3): c.254A> C (p.Glu85Ala)single nucleotide variantPathogenicrs199469625GRCh37Chr 5, 137034085: 137034085
21KLHL3NM_017415.2(KLHL3): c.1160T> C (p.Leu387Pro)single nucleotide variantPathogenicrs199469630GRCh37Chr 5, 136974701: 136974701
22KLHL3NM_017415.2(KLHL3): c.1280T> C (p.Met427Thr)single nucleotide variantPathogenicrs199469642GRCh37Chr 5, 136973024: 136973024
23KLHL3NM_017415.2(KLHL3): c.232A> G (p.Met78Val)single nucleotide variantPathogenicrs199469624GRCh37Chr 5, 137045448: 137045448
24KLHL3NM_017415.2(KLHL3): c.1501C> A (p.Pro501Thr)single nucleotide variantPathogenicrs199469634GRCh37Chr 5, 136964076: 136964076
25KLHL3NM_017415.2(KLHL3): c.430C> T (p.Gln144Ter)single nucleotide variantPathogenicrs199469637GRCh37Chr 5, 137028070: 137028070
26KLHL3NM_017415.2(KLHL3): c.926A> G (p.Gln309Arg)single nucleotide variantPathogenicrs199469627GRCh37Chr 5, 136975644: 136975644
27KLHL3NM_017415.2(KLHL3): c.1151G> A (p.Arg384Gln)single nucleotide variantPathogenicrs199469629GRCh37Chr 5, 136974710: 136974710
28KLHL3NM_017415.2(KLHL3): c.1292G> A (p.Arg431Gln)single nucleotide variantPathogenicrs199469643GRCh37Chr 5, 136973012: 136973012
29KLHL3NM_017415.2(KLHL3): c.1723C> T (p.Arg575Trp)single nucleotide variantPathogenicrs199469646GRCh37Chr 5, 136961454: 136961454
30KLHL3NM_017415.2(KLHL3): c.1295G> A (p.Ser432Asn)single nucleotide variantPathogenicrs199469631GRCh37Chr 5, 136973009: 136973009
31PIEZO2PIEZO2, 8-BP DEL, NT8238deletionPathogenic
32PIEZO2NM_022068.3(PIEZO2): c.8057G> A (p.Arg2686His)single nucleotide variantPathogenicGRCh38Chr 18, 10671729: 10671729
33CUL3CUL3, IVS8, A-G, -26single nucleotide variantPathogenic
34CUL3CUL3, IVS8, T-G, -28single nucleotide variantPathogenic
35CUL3CUL3, IVS8, T-G, -12single nucleotide variantPathogenic
36CUL3CUL3, IVS8, T-A, -5single nucleotide variantPathogenic
37CUL3CUL3, IVS8, C-T, -3single nucleotide variantPathogenic
38CUL3CUL3, IVS8, G-A, -1single nucleotide variantPathogenic
39CUL3NM_003590.4(CUL3): c.1238A> G (p.Asp413Gly)single nucleotide variantPathogenicrs199469656GRCh37Chr 2, 225368508: 225368508
40KLHL3KLHL3, TRP470TERsingle nucleotide variantPathogenic
41KLHL3NM_017415.2(KLHL3): c.965T> G (p.Phe322Cys)single nucleotide variantPathogenicrs199469639GRCh37Chr 5, 136975605: 136975605
42KLHL3NM_017415.2(KLHL3): c.1229C> T (p.Ser410Leu)single nucleotide variantPathogenicrs199469641GRCh37Chr 5, 136973075: 136973075
43KLHL3NM_017415.2(KLHL3): c.1583G> A (p.Arg528His)single nucleotide variantPathogenicrs199469636GRCh37Chr 5, 136963994: 136963994
44KLHL3NM_017415.2(KLHL3): c.718C> T (p.Arg240Ter)single nucleotide variantPathogenicrs199469638GRCh37Chr 5, 136997639: 136997639
45KLHL3NM_017415.2(KLHL3): c.1007G> T (p.Arg336Ile)single nucleotide variantPathogenicrs199469640GRCh37Chr 5, 136975563: 136975563
46KLHL3NM_017415.2(KLHL3): c.1670A> G (p.Tyr557Cys)single nucleotide variantPathogenicrs199469645GRCh37Chr 5, 136961507: 136961507
47KLHL3NM_017415.2(KLHL3): c.1582C> T (p.Arg528Cys)single nucleotide variantPathogenicrs199469635GRCh37Chr 5, 136963995: 136963995
48KLHL3NM_017415.2(KLHL3): c.1298G> A (p.Ser433Asn)single nucleotide variantPathogenicrs199469632GRCh37Chr 5, 136973006: 136973006
49KLHL3NM_017415.2(KLHL3): c.1193C> T (p.Ala398Val)single nucleotide variantPathogenicrs387907155GRCh37Chr 5, 136974668: 136974668
50KLHL3KLHL3, ASN529LYSsingle nucleotide variantPathogenic
51KLHL3NM_017415.2(KLHL3): c.1277C> T (p.Pro426Leu)single nucleotide variantPathogenicrs387907156GRCh37Chr 5, 136973027: 136973027
52WNK1NG_007984.2: g.18538_59810deldeletionPathogenicGRCh37Chr 12, 875762: 917034
53WNK1NC_000012.12: g.776558_798335del21778deletionPathogenicGRCh37Chr 12, 885724: 907501
54WNK4NM_032387.4(WNK4): c.1693C> G (p.Gln565Glu)single nucleotide variantPathogenicrs137853092GRCh37Chr 17, 40939512: 40939512
55WNK4NM_032387.4(WNK4): c.1684G> A (p.Glu562Lys)single nucleotide variantPathogenicrs137853093GRCh37Chr 17, 40939503: 40939503
56WNK4NM_032387.4(WNK4): c.1691A> C (p.Asp564Ala)single nucleotide variantPathogenicrs137853094GRCh37Chr 17, 40939510: 40939510
57WNK4NM_032387.4(WNK4): c.3553C> T (p.Arg1185Cys)single nucleotide variantPathogenicrs137853095GRCh37Chr 17, 40948262: 40948262

Expression for genes affiliated with Pseudohypoaldosteronism, Type Iie

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

Pathways for genes affiliated with Pseudohypoaldosteronism, Type Iie

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

idSuper pathways (with members indented)ScoreTop Affiliating Genes
Show member pathways
9.0WNK4, WNK1
29.0WNK4, WNK1
39.0WNK4, WNK1

Compounds for genes affiliated with Pseudohypoaldosteronism, Type Iie

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44Novoseek, 24HMDB, 11DrugBank
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Compounds related to Pseudohypoaldosteronism, Type Iie according to GeneCards Suite gene sharing:

idCompoundScoreTop Affiliating Genes
1thiazide449.2WNK4, WNK1
2chlorine44 2410.1WNK4, WNK1
3nacl449.0WNK1, WNK4
4proline449.0WNK4, WNK1
5chloride448.9WNK4, WNK1
6potassium44 24 1110.7WNK4, WNK1
7lysine448.7WNK4, WNK1, CUL3

GO Terms for genes affiliated with Pseudohypoaldosteronism, Type Iie

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

idNameGO IDScoreTop Affiliating Genes
1Cul3-RING ubiquitin ligase complexGO:00314639.5KLHL3, CUL3

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

(show all 9)
idNameGO IDScoreTop Affiliating Genes
1distal tubule morphogenesisGO:00721569.5KLHL3, WNK4
2renal sodium ion absorptionGO:00702949.4WNK4, KLHL3
3protein ubiquitinationGO:00165679.4CUL3, KLHL3
4ion homeostasisGO:00508019.4WNK4, KLHL3
5regulation of cellular processGO:00507949.2WNK4, WNK1
6negative regulation of pancreatic juice secretionGO:00901889.2WNK4, WNK1
7ion transportGO:00068119.0WNK4, WNK1
8protein phosphorylationGO:00064689.0WNK4, WNK1
9intracellular signal transductionGO:00355568.7WNK4, WNK1

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

idNameGO IDScoreTop Affiliating Genes
1protein serine/threonine kinase activityGO:00046749.0WNK4, WNK1
2chloride channel inhibitor activityGO:00198698.7WNK4, WNK1

Sources for Pseudohypoaldosteronism, Type Iie

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26ICD10 via Orphanet
34MESH via Orphanet
47OMIM via Orphanet
57SNOMED-CT via Orphanet
62UMLS via Orphanet