Liddle Syndrome malady

NIH Rare Diseases: Liddle syndrome is a rare, inherited form of high blood pressure (hypertension). The condition is characterized by severe, early-onset hypertension associated with decreased levels of potassium, renin and aldosterone in blood plasma. Children usually have no symptoms; adults can present with symptoms of low potassium levels (hypokalemia) such as weakness, fatigue, muscle pain (myalgia), constipation or palpitations. It is caused by mutations in either the SCNN1B or SCNN1G genes and is inherited in an autosomal dominant manner. Treatment may include a low sodium diet and potassium-sparing diuretics to reduce blood pressure and normalize potassium levels. Conventional anti-hypertensive therapies are not effective.³⁰

MalaCards: Liddle Syndrome, also known as pseudoaldosteronism, is related to pseudohypoaldosteronism and hypertension. An important gene associated with Liddle Syndrome is SCNN1B (sodium channel, non-voltage-gated 1, beta subunit), and among its related pathways are ACE Inhibitor Pathway, Pharmacodynamics and Sodium channels and transporters- inward current. The compounds 11alpha-hydroxyprogesterone and potassium canrenoate have been mentioned in the context of this disorder. Affiliated tissues include colon and b cells, and related mouse phenotypes are normal and renal/urinary system.

OMIM: 177200

Aliases & Descriptions:

liddle syndrome 6 7 30 8 33 43 pseudoaldosteronism 6 30

liddle's syndrome 30

Diseases related to liddle syndrome by text searches and GeneDecks gene sharing:

(show top 50)    (show all 67)

id	Related Disease	Score	Top Affiliating Genes
1	pseudohypoaldosteronism	27.8	SCNN1G, SCNN1B, SCNN1A, REN, CFTR, ASIC5
2	hypertension	27.3	NR3C1, NEDD4, NEDD4L, WNK4, CYP11B2, HSD11B2
3	essential hypertension	27.1	REN, SCNN1A, WNK4, SCNN1B, IGF1, HSD11B2
4	aldosteronism	26.4	IGF1, REN, NEDD4L, NR3C1, NR3C2, NEDD4
5	bronchiectasis with or without elevated sweat chloride 1	13.5	SCNN1B, CFTR
6	autosomal dominant pseudohypoaldosteronism type 1	13.5	SCNN1G, NR3C2
7	17-alpha-hydroxylase deficiency	13.5	CYP11B2, REN
8	pseudohypoaldosteronism type i	13.4	SCNN1A, SCNN1G, SCNN1B
9	11-beta-hydroxylase deficiency	13.4	REN, CYP11B2
10	hypoaldosteronism	13.4	REN, CYP11B2
11	hypertension with brachydactyly	13.4	NR3C2, REN
12	low renin hypertension	13.3	CYP11B2, HSD11B2, REN
13	familial hyperaldosteronism	13.3	CYP11B2, REN
14	apparent mineralocorticoid excess syndrome	13.3	HSD11B2, REN, NR3C2
15	anuria	13.3	REN, HSD11B2, NR3C2
16	adrenal adenoma	13.3	REN, CYP11B2, HSD11B2
17	cushing's syndrome	13.3	NR3C2, HSD11B2, NR3C1
18	conn's syndrome	13.2	NR3C2, REN, CYP11B2
19	abcb11-related intrahepatic cholestasis	13.2	REN, CYP11B2, NR3C2
20	enhanced s-cone syndrome	13.2	NR3C1, NR3C2
21	pseudohypoaldosteronism type ii	13.2	WNK4, SCNN1A, REN
22	cortisol resistance	13.2	NR3C1, HSD11B2
23	21-hydroxylase deficiency	13.2	CYP11B2, REN, NR3C1
24	ciliary dyskinesia	13.2	CFTR, SCNN1A, SCNN1B, SCNN1G
25	renal tubular acidosis	13.2	SCNN1G, REN, NR3C2
26	bronchiectasis	13.2	SCNN1A, SCNN1B, CFTR, SCNN1G
27	hellp syndrome	13.2	HSD11B2, CYP11B2, NR3C1
28	pulmonary edema	13.1	SCNN1A, REN, CYP11B2, CFTR
29	glucocorticoid resistance	13.0	NR3C2, NR3C1, HSD11B2, REN
30	congestive heart failure	13.0	NR3C2, REN, CYP11B2
31	hyperaldosteronism	12.9	CYP11B2, REN, SCNN1G, HSD11B2, NR3C2
32	delayed puberty	12.9	SCNN1B, IGF1, SCNN1A, REN
33	pre-eclampsia	12.8	REN, NR3C2, NR3C1, HSD11B2, CYP11B2
34	familial male-limited precocious puberty	12.8	IGF1, REN, NR3C1
35	atrial fibrillation	12.8	NR3C2, CYP11B2, NR3C1, REN, HSD11B2
36	familial hypercholesterolemia	12.8	NR3C1, SCNN1A, IGF1, CYP11B2
37	glucocorticoid-remediable aldosteronism	12.7	CYP11B2, NR3C1, REN, WNK4, NR3C2
38	addison's disease	12.7	NR3C1, REN, CYP11B2
39	portal hypertension	12.7	REN, IGF1, CFTR
40	fibromyalgia	12.7	NR3C1, NR3C2, IGF1
41	was-related disorders	12.6	CYP11B2, IGF1, CFTR, REN
42	hypokalemia	12.6	NR3C2, NR3C1, CYP11B2, HSD11B2, REN, CFTR
43	proteinuria	12.6	NR3C1, NR3C2, CYP11B2, HSD11B2, REN, CFTR
44	hyperandrogenism	12.6	NR3C1, REN, IGF1
45	eclampsia	12.5	CYP11B2, HSD11B2, SCNN1B, REN, IGF1
46	sinusitis	12.5	CFTR, SCNN1B, NR3C1, IGF1, SCNN1G
47	chronic kidney failure	12.5	NR3C2, REN, HSD11B2, IGF1, CYP11B2
48	nephrotic syndrome	12.5	NR3C2, NR3C1, HSD11B2, IGF1, REN
49	hypertrophy of breast	12.4	CYP11B2, IGF1, NR3C2, CFTR, REN
50	polycystic ovary syndrome	12.4	NR3C1, IGF1, NR3C2, CYP11B2, REN

Clinical features from OMIM: 177200

Approved drugs:

Drug clinical trials:

MalaCards organs/tissues related to liddle syndrome:

²²

id	Organ / Tissue -> Anatomical Compartment -> Cell	Relevance
1	Kidney -> Renal Collecting Duct System -> Collecting Duct Cells	Potential therapeutic candidate, affected by disease

MGI Mouse Phenotypes related to liddle syndrome:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	normal phenotype	MP:0002873	8.6	HSD11B2, IGF1, CFTR, SCNN1G, SCNN1B, SCNN1A
2	renal/urinary system phenotype	MP:0005367	8.5	REN, WNK4, NEDD4L, NR3C2, NR3C1, CYP11B2
3	respiratory system phenotype	MP:0005388	8.4	NEDD4L, NR3C1, IGF1, CFTR, SCNN1G, SCNN1B
4	cardiovascular system phenotype	MP:0005385	8.1	WNK4, NEDD4L, NEDD4, NR3C2, NR3C1, CYP11B2
5	homeostasis/metabolism phenotype	MP:0005376	7.6	CYP11B2, NR3C1, NR3C2, NEDD4L, WNK4, HSD11B2
6	mortality/aging	MP:0010768	7.6	CYP11B2, NR3C1, NR3C2, NEDD4, NEDD4L, HSD11B2

Articles related to liddle syndrome:

(show all 29)

id	Title	Authors	Year	Affiliating Genes
1	A clinical phenotype mimicking essential hypertension in a newly discovered family with Liddle's syndrome. (21525970)	Rossi E.... Casali B.	2011	SCNN1B
2	Liddle's syndrome caused by a novel mutation of the gamma-subunit of epithelial sodium channel gene SCNN1G in Chinese (20376790)	Shi J.Y.... Tian H.M.	2010	SCNN1B, SCNN1G
3	A novel mutation in the beta-subunit of the epithelial sodium channel gene (SCNN1B) in a Thai family with Liddle's syndrome. (19344079)	Sawathiparnich P.... Limwongse C.	2009	SCNN1B
4	Role of the UPS in Liddle syndrome. (19007435)	Rotin D.	2008	NEDD4L
5	Liddle's syndrome caused by a novel missense mutation (P617L) of the epithelial sodium channel beta subunit. (18398334)	Rossi E.... Staub O.	2008	SCNN1B
6	Aldosterone responsiveness of the epithelial sodium channel (ENaC) in colon is increased in a mouse model for Liddle's syndrome. (18006588)	Bertog M.... Korbmacher C.	2008	SCNN1A, SCNN1B, SCNN1G
7	Mutation analysis of SCNN1B in a family with Liddle's syndrome. (16943574)	Wang W.... Ning G.	2006	NEDD4, SCNN1B, SCNN1G
8	Liddle's syndrome mutations increase Na+ transport through dual effects on epithelial Na+ channel surface expression and proteolytic cleavage. (16477034)	Knight K.K.... Snyder P.M.	2006	NEDD4L, UBE2E3
9	Liddle's syndrome caused by a novel mutation in the proline-rich PY motif of the epithelial sodium channel beta-subunit. (15483078)	Furuhashi M.... Shimamoto K.	2005	SCNN1B, ASIC5
10	A novel epithelial sodium channel beta-subunit mutation associated with hypertensive Liddle syndrome. (15690192)	Freundlich M.... Ludwig M.	2005	REN, SCNN1B
11	Vasopressin-stimulated CFTR Cl- currents are increased in the renal collecting duct cells of a mouse model of Liddle's syndrome. (15513933)	Chang C.T.... Vandewalle A.	2005	CFTR
12	Liddle's syndrome associated with a point mutation in the extracellular domain of the epithelial sodium channel gamma subunit. (12473862)	Hiltunen T.P.... Kontula K.	2002	SCNN1G
13	A frameshift mutation of beta subunit of epithelial sodium channel in a case of isolated Liddle syndrome. (12473861)	Nakano Y.... Oshima T.	2002	SCNN1B
14	A study of mutation(s) of the epithelial sodium chan nel gene in a Liddle's syndrome family (11798604)	Ma X.... Guo X.	2001	REN
15	Diagnosis of Liddle syndrome by genetic analysis of beta and gamma subunits of epithelial sodium channel--a report of five affected family members. (11393671)	Gao P.J.... Yang L.W.	2001	SCNN1B, SCNN1G
16	Disorders of the epithelial Na(+) channel in Liddle's syndrome and autosomal recessive pseudohypoaldosteronism type 1. (11014928)	Oh Y.S.... Warnock D.G.	2000	SCNN1G
17	Quantitative trait loci for blood pressure exist near the IGF-1, the Liddle syndrome, the angiotensin II-receptor gene and the renin loci in man. (10446938)	Nagy Z.... Luft F.C.	1999	IGF1, REN
18	Defective regulation of the epithelial Na+ channel by Nedd4 in Liddle's syndrome. (10074483)	Abriel H.... Staub O.	1999	NEDD4
19	Inhibition of the epithelial Na+ channel by interaction of Nedd4 with a PY motif deleted in Liddle's syndrome. (9792722)	Goulet C.C.... Snyder P.M.	1998	NEDD4
20	Genetic analysis of the epithelial sodium channel in Liddle's syndrome. (9794716)	Uehara Y.... Arakawa K.	1998	SCNN1B
21	A family with Liddle's syndrome caused by a new missense mutation in the beta subunit of the epithelial sodium channel. (9626162)	Inoue J.... Tomita K.	1998	SCNN1B
22	Liddle's syndrome: a 14-year follow-up of the youngest diagnosed case. (9035163)	Vania A.... Cugini P.	1997	REN
23	Genotype-phenotype analysis of a newly discovered family with Liddle's syndrome. (9350583)	Jeunemaitre X.... Barbry P.	1997	SCNN1B
24	WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle's syndrome. (8665844)	Staub O.... Rotin D.	1996	NEDD4
25	Cell surface expression of the epithelial Na channel and a mutant causing Liddle syndrome: a quantitative approach. (8986818)	Firsov D.... Rossier B.C.	1996	SCNN1A, SCNN1B, SCNN1G
26	Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. (7550319)	Hansson J.H.... Lifton R.P.	1995	SCNN1B, SCNN1G
27	A de novo missense mutation of the beta subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity. (8524790)	Hansson J.H.... Lifton R.P.	1995	SCNN1B
28	Mechanism by which Liddle's syndrome mutations increase activity of a human epithelial Na+ channel. (8521520)	Snyder P.M.... Welsh M.J.	1995	SCNN1B, SCNN1G
29	Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. (7954808)	Shimkets R.A.... Lifton R.P.	1994	SCNN1B

Genes related to liddle syndrome according to GeneCards:

(show all 23)

id	Symbol	Description	Score	GeneCards Section Context
1	SCNN1B	sodium channel, non-voltage-gated 1, beta subunit	11.1	Publications, Orthologs, Summaries
2	SCNN1G	sodium channel, non-voltage-gated 1, gamma subunit	11.1	Publications, Orthologs, Summaries
3	SCNN1A	sodium channel, non-voltage-gated 1 alpha subunit	11.0	Publications, Orthologs
4	NEDD4	neural precursor cell expressed, developmentally down-regulated 4, E3 ubiquitin protein ligase	11.0	Publications
5	HSD11B2	hydroxysteroid (11-beta) dehydrogenase 2	11.0
6	REN	renin	11.0	Publications
7	CYP11B2	cytochrome P450, family 11, subfamily B, polypeptide 2	11.0
8	NEDD4L	neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase	11.0	Publications
9	NR3C1	nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor)	11.0
10	NR3C2	nuclear receptor subfamily 3, group C, member 2	11.0
11	CFTR	cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)	11.0	Publications
12	SCNN1D	sodium channel, non-voltage-gated 1, delta subunit	11.0	Orthologs
13	WNK4	WNK lysine deficient protein kinase 4	11.0
14	HERC5	HECT and RLD domain containing E3 ubiquitin protein ligase 5	11.0	Disorders
15	ASIC5	acid-sensing (proton-gated) ion channel family member 5	11.0	Publications, Disorders
16	UBE2S	ubiquitin-conjugating enzyme E2S	11.0	Disorders
17	UBE2E3	ubiquitin-conjugating enzyme E2E 3	11.0	Publications
18	UBE2K	ubiquitin-conjugating enzyme E2K	11.0
19	SEC24D	SEC24 family, member D (S. cerevisiae)	11.0	Disorders
20	WWP1	WW domain containing E3 ubiquitin protein ligase 1	11.0
21	HECW1	HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1	11.0	Orthologs
22	HECW2	HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2	11.0	Orthologs
23	IGF1	insulin-like growth factor 1 (somatomedin C)	11.0	Publications

Pathways related to liddle syndrome according to GeneDecks:

(show all 14)

id	Pathway	Score	Top Affiliating Genes
1	ACE Inhibitor Pathway, Pharmacodynamics34	10.3	NR3C2
2	Sodium channels and transporters- inward current10	9.9	SCNN1G, SCNN1B, SCNN1A, SCNN1D
3	Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics34	9.9	REN, CYP11B2, NR3C2
4	Aldosterone-regulated sodium reabsorption20	9.8	SCNN1A, SCNN1B, HSD11B2, NR3C2, NEDD4L
5	GHRH Signaling36	9.7	SCNN1G, SCNN1B, SCNN1A, SCNN1D
6	NO-dependent CFTR activation (normal and CF)41	9.7	CFTR, SCNN1G, SCNN1B, SCNN1A, SCNN1D
7	Aldosterone Signaling in Epithelial Cells36	9.7	SCNN1D, SCNN1A, SCNN1B, SCNN1G, NEDD4
8	Taste transduction20	9.7	SCNN1G, SCNN1B, SCNN1A
9	Neuropathic Pain-Signaling in Dorsal Horn Neurons36	9.6	SCNN1D, SCNN1A, SCNN1B, SCNN1G
10	Cholera Infection36	9.6	CFTR, SCNN1G, SCNN1B, SCNN1A, SCNN1D
11	CFTR-dependent regulation of ion channels in Airway Epithelium (norm and CF)41	9.5	NEDD4, CFTR, SCNN1G, SCNN1B, SCNN1A, SCNN1D
12	Protein Stability3	9.3	NEDD4L, NEDD4, UBE2S, UBE2K, REN
13	Activation of cAMP-Dependent PKA36	9.2	SCNN1D, SCNN1A, SCNN1B, SCNN1G, IGF1
14	Ubiquitin mediated proteolysis20	8.7	NEDD4L, NEDD4, WWP1, UBE2S, UBE2E3, UBE2K

Compounds related to liddle syndrome according to GeneDecks:

(show top 50)    (show all 53)

id	Compound	Score	Top Affiliating Genes
1	11alpha-hydroxyprogesterone32	10.4	NR3C2, HSD11B2
2	potassium canrenoate32	10.3	NR3C2, NR3C1
3	allotetrahydrocortisol32	10.3	NR3C2, HSD11B2
4	cortisone acetate32 9 9	12.3	NR3C1, HSD11B2
5	tetrahydrocortisol32 18	11.3	NR3C2, HSD11B2
6	tetrahydrocortisone32 18	11.2	NR3C2, HSD11B2
7	18-hydroxycorticosterone32 18	11.2	CYP11B2, REN
8	tetrahydroaldosterone32	10.2	NR3C2, CYP11B2, REN
9	11-dehydrocorticosterone32 18	11.2	HSD11B2, NR3C1, NR3C2
10	Aldosterone9 18 9	12.2	CYP11B2, NR3C1, NR3C2
11	metyrapone32 42 9 9	13.2	CYP11B2, NR3C1, NR3C2
12	fluticasone propionate32 42 9 9	13.1	HSD11B2, NR3C1, NR3C2
13	triamcinolone acetonide32	10.1	CFTR, NR3C1, NR3C2
14	carbenoxolone32 9 9	12.0	NR3C2, NR3C1, HSD11B2, REN
15	glycyrrhetinic acid32 18	11.0	NR3C2, NR3C1, HSD11B2, REN
16	hydrochlorothiazide32 34 9 18 9	14.0	REN, HSD11B2, CYP11B2, NR3C2
17	fludrocortisone32 9 9	12.0	REN, CYP11B2, NR3C1, NR3C2
18	glycyrrhizin32	10.0	REN, HSD11B2, NR3C1, NR3C2
19	eplerenone32 42 9 9	13.0	NR3C2, NR3C1, CYP11B2, REN
20	11 deoxycortisol32	10.0	NR3C2, NR3C1, CYP11B2, REN
21	thiazide32	10.0	REN, SCNN1A, NR3C2, WNK4
22	ang ii32	10.0	NR3C2, CYP11B2, REN
23	3beta-hydroxysteroid32	9.9	HSD11B2, CYP11B2, NR3C2
24	triamterene32 9 18 9	12.9	NR3C2, SCNN1G, SCNN1B, SCNN1A, SCNN1D
25	doca32	9.8	NR3C2, NR3C1, CYP11B2, HSD11B2, REN
26	spironolactone32 42 34 9 9	13.8	NR3C2, NR3C1, CYP11B2, HSD11B2, REN
27	11beta-hydroxysteroid32	9.8	NR3C2, NR3C1, CYP11B2, HSD11B2, REN
28	corticosterone32 18	10.8	NR3C2, NR3C1, CYP11B2, HSD11B2, REN
29	drospirenone32 34 9 9	12.7	REN, NR3C2
30	nandrolone32 18	10.7	IGF1, NR3C1
31	androstenedione32 18	10.7	CYP11B2, HSD11B2, IGF1, REN
32	losartan32 34 9 9	12.7	NR3C2, CYP11B2, IGF1, REN
33	norepinephrine32 9 18 9	12.7	REN, CFTR, HSD11B2, CYP11B2, NR3C2
34	nacl32	9.6	WNK4, NR3C2, ASIC5, SCNN1A, REN
35	dihydrotestosterone32 9 18 9	12.6	NR3C2, NR3C1, HSD11B2, IGF1
36	cortisone32 18	10.5	IGF1, HSD11B2, CYP11B2, NR3C1, NR3C2
37	dhea32	9.5	NR3C2, NR3C1, CYP11B2, HSD11B2, IGF1
38	potassium32 9 18 9	12.4	WNK4, NR3C2, CYP11B2, HSD11B2, REN
39	chloride32	9.4	WNK4, NR3C2, CFTR, REN
40	hydrocortisone32 9 9	11.3	NR3C2, NR3C1, CYP11B2, HSD11B2, IGF1, REN
41	acth32	9.3	NR3C2, NR3C1, CYP11B2, HSD11B2, IGF1, REN
42	progesterone32 42 9 18 9	13.2	NR3C2, NR3C1, CYP11B2, HSD11B2, IGF1, SCNN1G
43	amiloride32 9 9	11.1	NR3C2, ASIC5, CFTR, SCNN1G, SCNN1B, SCNN1A
44	estradiol32 9 18 9	12.1	REN, IGF1, HSD11B2, NR3C1, NR3C2
45	dopamine32 9 18 9	12.0	NR3C2, NR3C1, IGF1, ASIC5, CFTR, REN
46	steroid32	8.8	NR3C2, NR3C1, CYP11B2, HSD11B2, IGF1, UBE2E3
47	actinomycin d32	8.8	NR3C2, NR3C1, HSD11B2, IGF1, CFTR, UBE2K
48	dexamethasone32 42 34 9 9	12.8	NR3C2, NR3C1, CYP11B2, HSD11B2, IGF1, CFTR
49	cysteine32	8.7	NEDD4L, NEDD4, NR3C2, HSD11B2, CFTR, UBE2E3
50	sodium32 18	8.1	REN, WNK4, NEDD4L, NEDD4, WWP1, NR3C2

Cellular components related to liddle syndrome according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	apical plasma membrane	GO:016324	9.7	SCNN1A, SCNN1B, SCNN1G, CFTR
2	sodium channel complex	GO:034706	9.7	SCNN1A, SCNN1B, SCNN1G

Biological processes related to liddle syndrome according to GeneDecks:

(show all 10)

id	Name	GO ID	Score	Top Affiliating Genes
1	regulation of blood volume by renal aldosterone	GO:002017	10.4	HSD11B2
2	wound healing, spreading of epidermal cells	GO:035313	10.1	SCNN1B, SCNN1G
3	regulation of potassium ion transmembrane transporter activity	GO:1901016	10.1	NEDD4L, NEDD4
4	regulation of ion transmembrane transport	GO:034765	10.1	NEDD4L, NEDD4
5	excretion	GO:007588	9.9	SCNN1A, SCNN1B, SCNN1G, NEDD4L
6	sensory perception of taste	GO:050909	9.9	SCNN1G, SCNN1B, SCNN1A, SCNN1D
7	negative regulation of sodium ion transport	GO:010766	9.8	NEDD4, NEDD4L
8	protein K63-linked ubiquitination	GO:070534	9.7	NEDD4, UBE2S, UBE2E3
9	sodium ion transport	GO:006814	9.7	SCNN1D, SCNN1A, SCNN1B, SCNN1G, NEDD4L
10	water homeostasis	GO:030104	9.6	NEDD4L, IGF1

Molecular functions related to liddle syndrome according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	sodium channel inhibitor activity	GO:019871	10.1	NEDD4, NEDD4L
2	WW domain binding	GO:050699	9.9	SCNN1G, SCNN1B, SCNN1A
3	steroid binding	GO:005496	9.5	HSD11B2, NR3C1, NR3C2
4	ligand-gated sodium channel activity	GO:015280	9.4	SCNN1D, SCNN1A, SCNN1B, SCNN1G, ASIC5
5	ubiquitin-protein ligase activity	GO:004842	8.4	NEDD4L, NEDD4, WWP1, UBE2S, UBE2E3, UBE2K