Pseudohypoaldosteronism Type Ii malady

NIH Rare Diseases: 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.³⁰

MalaCards: Pseudohypoaldosteronism Type Ii, also known as pseudohypoaldosteronism type 2, is related to liddle syndrome and pseudohypoaldosteronism. An important gene associated with Pseudohypoaldosteronism Type Ii is PHA2A (Pseudohypoaldosteronism type II (gene A)), and among its related pathways are PI3K / Akt Signaling and Aldosterone-regulated sodium reabsorption. The compounds bendroflumethiazide and hydrochlorothiazide have been mentioned in the context of this disorder. Affiliated tissues include kidney, and related mouse phenotypes are cardiovascular system and renal/urinary system.

Genetics Home Reference: 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.¹⁷

OMIM: 145260

GeneReviews summary for pha2

pseudohypoaldosteronism type ii 7 15 33 pseudohypoaldosteronism type 2 15 30 16 17 gordon syndrome 30 16 32 pha2 15 30 16 gordon hyperkalemia-hypertension syndrome 30 17 familial hyperkalemiahypertension 15 16 pseudohypoaldosteronism, type ii 33 43 phaii 15 16 arthrogryposis multiplex congenita, distal, type iia 43 arthrogryposis multiplex congenita distal type 2a 30 hyperpotassemia and hypertension, familial 43

familial hyperpotassemia and hypertension 17 camptodactyly, cleft palate, and clubfoot 30 hyperpotassemia and hypertension familial 30 familial hypertensive hyperkalemia 17 arthrogryposis distal type 3 30 distal arthrogryposis type 3 30 chloride shunt syndrome 30 pseudohypoaldosteronism 43 gordon’s syndrome 15 da3 30

Disease types for pseudohypoaldosteronism family:

pseudohypoaldosteronism type i	pseudohypoaldosteronism type ii
pseudohypoaldosteronism type iib	pseudohypoaldosteronism type iic
pseudohypoaldosteronism type iid	pseudohypoaldosteronism type iie

Diseases related to pseudohypoaldosteronism type ii by text searches and GeneDecks gene sharing:

(show top 50)    (show all 163)

id	Related Disease	Score	Top Affiliating Genes
1	liddle syndrome	27.6	WNK4, SCNN1A, REN
2	pseudohypoaldosteronism	27.2	REN, WNK4, KCNJ1, SCNN1A, PHA2A, SLC12A3
3	aldosteronism	26.1	WNK4, WNK1, SLC12A3, SCNN1A, KCNJ1, REN
4	hypercalciuria	25.7	WNK4, WNK1, SLC12A3, KCNJ1, REN
5	osteoporosis	25.3	SLC12A3, WNK1, WNK4
6	hypertension	25.0	WNK4, WNK3, WNK2, WNK1, SLC12A3, SCNN1A
7	essential hypertension	24.0	WNK4, WNK1, SLC12A3, SCNN1A, KCNJ1, REN
8	autosomal dominant disease	12.9	WNK1, WNK4
9	bartter syndrome, type 2	12.9	KCNJ1, REN
10	glucocorticoid-remediable aldosteronism	12.9	REN, WNK4
11	bartter syndrome antenatal type 2	12.9	REN, KCNJ1
12	polyhydramnios	12.9	SLC12A3, KCNJ1
13	high blood pressure	12.8	REN, WNK1
14	abcb11-related intrahepatic cholestasis	12.8	KCNJ1, REN
15	renal hypertension	12.8	REN, SLC12A3
16	dent disease	12.8	REN, SLC12A3
17	hypomagnesemia	12.8	REN, SLC12A3
18	autonomic neuropathy	12.7	REN, WNK1
19	nephrocalcinosis	12.7	KCNJ1, SLC12A3
20	nephrolithiasis	12.6	KCNJ1, SLC12A3
21	autonomic dysfunction	12.6	REN, WNK1
22	delayed puberty	12.5	REN, SCNN1A
23	bartter syndrome type 3	12.5	SLC12A3, KCNJ1, REN
24	bartter disease	12.4	REN, KCNJ1, SLC12A3
25	hyperaldosteronism	12.4	REN, KCNJ1, SLC12A3
26	hypokalemia	12.4	REN, KCNJ1, SLC12A3
27	pulmonary edema	12.2	REN, SCNN1A
28	gitelman syndrome	12.1	REN, KCNJ1, SLC12A3, WNK1
29	cystic fibrosis	11.7	WNK4, SCNN1A, KCNJ1, REN
30	arthrogryposis	8.9
31	venencie powell gordon winkelmann syndrome	8.9
32	arthrogryposis distal type 2b	8.6
33	freeman sheldon syndrome	8.6
34	distal arthrogryposis type 5	8.2
35	arthrogryposis multiplex congenita distal type 1	8.2
36	leukemia	8.0
37	arthrogryposis, distal, type 2e	7.7
38	arthrogryposis, distal, type 1b	7.7
39	trismus-pseudocamptodactyly syndrome	7.7
40	carcinoma	7.7
41	hepatitis	7.5
42	arthritis	7.2
43	autosomal recessive pseudohypoaldosteronism type 1	7.2
44	pseudohypoaldosteronism type iid	7.0
45	pseudohypoaldosteronism type iie	7.0
46	rheumatoid arthritis	7.0
47	t-cell leukemia	7.0
48	hypoxia	6.9
49	myeloid leukemia	6.9
50	arthrogryposis-like hand anomaly and sensorineural deafness	6.8

Clinical features from OMIM: 145260

Approved drugs:

Drug clinical trials:

MalaCards organs/tissues related to pseudohypoaldosteronism type ii:

²²

MGI Mouse Phenotypes related to pseudohypoaldosteronism type ii:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	cardiovascular system phenotype	MP:0005385	7.8	KCNJ1, SLC12A3, WNK1, WNK3, WNK4, REN
2	renal/urinary system phenotype	MP:0005367	6.9	WNK4, REN, KCNJ1, SCNN1A, SLC12A3, WNK1
3	homeostasis/metabolism phenotype	MP:0005376	6.7	WNK4, WNK3, WNK1, SLC12A3, SCNN1A, KCNJ1

Articles related to pseudohypoaldosteronism type ii:

id	Title	Authors	Year	Affiliating Genes
1	Identification of a novel WNK4 mutation in Chinese pa tients with pseudohypoaldosteronism type II. (21196779)	Zhang C.... Chen N.	2011	SLC12A3, WNK4
2	A patient with pseudohypoaldosteronism type II caused by a novel mutation in WNK4 gene. (19016006)	Gong H.... Ning G.	2008	WNK4
3	A new kindred with pseudohypoaldosteronism type II and a novel mutation (564D>H) in the acidic motif of the WNK4 gene. (15998707)	Golbang A.P.... O'Shaughnessy K.M.	2005	KCNJ1, SLC12A3, WNK4
4	A new locus on chromosome 12p13.3 for pseudohypoaldosteronism type II, an autosomal dominant form of hypertension. (10869238)	Disse-Nicodeme S.... Jeunemaitre X.	2000	REN, SCNN1A, WNK1

Genes related to pseudohypoaldosteronism type ii according to GeneCards:

id	Symbol	Description	Score	GeneCards Section Context
1	PHA2A	Pseudohypoaldosteronism type II (gene A)	11.1	Aliases & Descriptions, Summaries
2	WNK1	WNK lysine deficient protein kinase 1	11.1	Publications, Orthologs, Summaries
3	WNK4	WNK lysine deficient protein kinase 4	11.0	Publications, Orthologs
4	SLC12A3	solute carrier family 12 (sodium/chloride transporters), member 3	11.0	Publications
5	KCNJ1	potassium inwardly-rectifying channel, subfamily J, member 1	11.0	Publications
6	WNK3	WNK lysine deficient protein kinase 3	11.0	Orthologs
7	WNK2	WNK lysine deficient protein kinase 2	11.0	Orthologs
8	SCNN1A	sodium channel, non-voltage-gated 1 alpha subunit	11.0	Publications
9	REN	renin	11.0	Publications

Pathways related to pseudohypoaldosteronism type ii according to GeneDecks:

id	Pathway	Score	Top Affiliating Genes
1	PI3K / Akt Signaling3	9.8	WNK1, WNK4
2	Aldosterone-regulated sodium reabsorption20	8.9	KCNJ1, SCNN1A

Compounds related to pseudohypoaldosteronism type ii according to GeneDecks:

(show all 14)

id	Compound	Score	Top Affiliating Genes
1	bendroflumethiazide32 9 9	11.7	REN, SLC12A3
2	hydrochlorothiazide32 34 9 18 9	13.6	SLC12A3, REN
3	furosemide32 42 34 9 18 9	14.5	SLC12A3, REN
4	chlorine32 18	10.5	WNK1, WNK4, SLC12A3
5	amiloride32 9 9	11.1	SCNN1A, REN
6	lysine32	9.0	WNK1, KCNJ1, SLC12A3, WNK4
7	chloride32	8.6	WNK1, WNK4, SLC12A3, KCNJ1, REN
8	potassium32 9 18 9	11.6	WNK4, WNK1, SLC12A3, REN, KCNJ1
9	adp32 18	9.5	WNK3, WNK2, WNK4, WNK1
10	magnesium32 9 18 9	11.4	KCNJ1, WNK2, WNK3, WNK4, WNK1
11	Adenosine triphosphate9 18 9	10.3	WNK1, WNK2, WNK3, WNK4
12	thiazide32	8.3	SLC12A3, SCNN1A, WNK1, WNK4, REN
13	nacl32	7.8	SLC12A3, SCNN1A, WNK1, KCNJ1, WNK4, REN
14	sodium32 18	8.8	WNK4, WNK1, SLC12A3, SCNN1A, KCNJ1, REN

Biological processes related to pseudohypoaldosteronism type ii according to GeneDecks:

(show all 8)

id	Name	GO ID	Score	Top Affiliating Genes
1	regulation of cellular process	GO:050794	9.9	WNK4, WNK1
2	regulation of ion homeostasis	GO:2000021	9.4	WNK2, WNK3
3	positive regulation of sodium ion transmembrane transporter activity	GO:2000651	9.4	WNK2, WNK3
4	ion transport	GO:006811	9.2	SLC12A3, WNK1, WNK4
5	sodium ion transport	GO:006814	9.2	SCNN1A, SLC12A3
6	excretion	GO:007588	8.9	SCNN1A, KCNJ1
7	intracellular protein kinase cascade	GO:007243	8.8	WNK2, WNK3, WNK4, WNK1
8	protein phosphorylation	GO:006468	8.6	WNK1, WNK2, WNK3, WNK4

Molecular functions related to pseudohypoaldosteronism type ii according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	protein serine/threonine kinase activity	GO:004674	8.3	WNK1, WNK2, WNK3, WNK4
2	ATP binding	GO:005524	8.2	KCNJ1, WNK1, WNK2, WNK3, WNK4