SCNN1B

Summary

SCNN1B (sodium channel epithelial 1 subunit beta, HGNC:10600) is a protein-coding gene on chromosome 16p12.2, encoding Epithelial sodium channel subunit beta (P51168). This is one of the three pore-forming subunits of the heterotrimeric epithelial sodium channel (ENaC), a critical regulator of sodium balance and fluid homeostasis.

Nonvoltage-gated, amiloride-sensitive, sodium channels control fluid and electrolyte transport across epithelia in many organs. These channels are heteromeric complexes consisting of 3 subunits: alpha, beta, and gamma. This gene encodes the beta subunit, and mutations in this gene have been associated with pseudohypoaldosteronism type 1 (PHA1), and Liddle syndrome.

Source: NCBI Gene 6338 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Liddle syndrome 1 (Definitive, GenCC) — +4 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 468 total — 19 pathogenic, 22 likely-pathogenic
• Phenotypes (HPO): 61
• Druggable target: yes
• MANE Select transcript: NM_000336

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10600
Approved symbol	SCNN1B
Name	sodium channel epithelial 1 subunit beta
Location	16p12.2
Locus type	gene with protein product
Status	Approved
Aliases	ENaCbeta
Ensembl gene	ENSG00000168447
Ensembl biotype	protein_coding
OMIM	600760
Entrez	6338

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 28 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000307331, ENST00000343070, ENST00000564275, ENST00000566441, ENST00000566647, ENST00000566870, ENST00000568085, ENST00000568923, ENST00000569789, ENST00000890249, ENST00000890250, ENST00000890251, ENST00000890252, ENST00000890253, ENST00000890254, ENST00000890255, ENST00000890256, ENST00000890257, ENST00000890258, ENST00000890259, ENST00000928026, ENST00000928027, ENST00000928028, ENST00000928029, ENST00000928030, ENST00000962244, ENST00000962245, ENST00000962246, ENST00000962247, ENST00000962248, ENST00000962249, ENST00000962250

RefSeq mRNA: 2 — MANE Select: NM_000336 NM_000336, NM_001410900

CCDS: CCDS10609, CCDS92127

Canonical transcript exons

ENST00000343070 — 13 exons

Exon	Start	End
ENSE00001177354	23352801	23353074
ENSE00001177411	23355299	23355489
ENSE00001287896	23302302	23302437
ENSE00001289677	23380421	23381294
ENSE00003459238	23378706	23378767
ENSE00003497231	23377329	23377386
ENSE00003534152	23371776	23371883
ENSE00003537699	23348592	23348910
ENSE00003545226	23380094	23380169
ENSE00003587371	23375738	23375855
ENSE00003611525	23377165	23377240
ENSE00003731067	23367856	23367959
ENSE00003738240	23371299	23371462

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 97.32.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8017 / max 537.0073, expressed in 291 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153155	1.2078	246
153154	0.5939	184

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.32	gold quality
esophagus mucosa	UBERON:0002469	94.11	gold quality
rectum	UBERON:0001052	91.87	gold quality
transverse colon	UBERON:0001157	91.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.16	gold quality
skin of abdomen	UBERON:0001416	90.96	gold quality
skin of leg	UBERON:0001511	90.55	gold quality
right lung	UBERON:0002167	90.23	gold quality
minor salivary gland	UBERON:0001830	89.75	gold quality
upper lobe of left lung	UBERON:0008952	88.78	gold quality
mouth mucosa	UBERON:0003729	88.27	gold quality
upper lobe of lung	UBERON:0008948	87.89	gold quality
vagina	UBERON:0000996	87.61	gold quality
zone of skin	UBERON:0000014	87.39	gold quality
mucosa of transverse colon	UBERON:0004991	87.13	gold quality
saliva-secreting gland	UBERON:0001044	86.74	gold quality
nasal cavity epithelium	UBERON:0005384	85.30	gold quality
body of stomach	UBERON:0001161	83.78	gold quality
epithelium of bronchus	UBERON:0002031	83.78	gold quality
bronchus	UBERON:0002185	83.16	gold quality
esophagus	UBERON:0001043	82.68	gold quality
adult mammalian kidney	UBERON:0000082	82.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.47	gold quality
bronchial epithelial cell	CL:0002328	81.81	gold quality
colon	UBERON:0001155	81.81	gold quality
large intestine	UBERON:0000059	81.72	gold quality
buccal mucosa cell	CL:0002336	81.24	gold quality
cervix squamous epithelium	UBERON:0006922	80.83	silver quality
tongue squamous epithelium	UBERON:0006919	80.43	silver quality
subcutaneous adipose tissue	UBERON:0002190	80.42	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	24.77
E-ANND-3	yes	11.85
E-CURD-114	yes	11.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1

miRNA regulators (miRDB)

32 targeting SCNN1B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-7111-3P	97.80	66.75	1467
HSA-MIR-634	97.74	67.11	818
HSA-MIR-647	97.73	67.79	927
HSA-MIR-4723-3P	97.67	65.91	1017
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-6769B-3P	97.41	65.53	1036
HSA-MIR-3183	97.40	65.68	978
HSA-MIR-125A-3P	97.04	66.92	902

Literature-anchored findings (GeneRIF, showing 40)

• Genotypes of the betaENaC gene have little influence on blood pressure level in the Japanese population. (PMID:11863256)
• cloned and characterized the 5’ end of the human beta-ENaC gene and identified alternate promoters that determine basal expression of separate transcripts (PMID:11934701)
• Novel mutations responsible for autosomal recessive multisystem pseudohypoaldosteronism and sequence variants in epithelial sodium channel beta-subunit gene. (PMID:12107247)
• homozygous mutation in the promoter region of betaENaC leads to pseudohypoaldosteronism type I, the first description of a mutation in the regulatory regions of an ENaC subunit leading to a clinical phenotype (PMID:12204893)
• Frameshift mutation of beta subunit caused by single cytosine insertion at codon 595, introducing new stop codon at 605 and deleting last 34 amino acids from normally encoded protein. (PMID:12473861)
• R563Q, a new variant of the beta epithelial sodium channel, is associated with low-renin, low-aldosterone hypertension. Only a minority of individuals with the R563Q allelle fully express the Liddle’s syndrome phenotype. (PMID:12714866)
• No support for an important role for the T594M variant of the ENaC gene contributing to either the development or severity of hypertension in subjects of African ancestry. (PMID:14553964)
• in ulcerative colitis, elevated proinflammatory cytokines selectively impair beta- and gamma-ENaC expression, which contributes to diarrhea by reducing colonic sodium absorption. (PMID:15188166)
• The roles of these missense mutations in the SCNN1B or SCNN1G gene identified in hypertensive patients are not clear in the pathogenesis of hypertension and the regulation of electrolytes. (PMID:15198480)
• cAMP regulates ENaC in part by phosphorylation and inhibition of Nedd4-2. Moreover, Nedd4-2 is a central convergence point for kinase regulation of Na(+) transport. (PMID:15328345)
• The ENaC expressed in the bladder epithelium might be implicated in the mechanosensory transduction in the bladder afferent pathways, thereby inducing detrusor instability by outlet obstruction. (PMID:15596218)
• Common variants of the ENaC beta subunit confer susceptibility to human essential hypertension. (PMID:15661075)
• the interactions of delta-ENaC with alpha beta gamma-human epithelial sodium channel subunits could account for heterogeneity of native epithelial channels (PMID:16423824)
• concluded that the T594M allele does not contribute significantly to blood pressure in blacks and does not predict a significantly superior response to amiloride therapy (PMID:16432044)
• SCNN1B is a modulator in Cystic fibrosis. (PMID:16463024)
• P616H mutation may be the underlying cause for the signs and symptoms of Liddle’s syndrome. (PMID:16943574)
• Concerted action of short chain fatty acids and corticosteroid hormones is required for induction of ENaC and maintenance of intestinal electrogenic sodium absorption (PMID:17241874)
• Results support a model whereby ubiquitin and clathrin adaptor binding sites act in concert to remove ENaC from the cell surface. (PMID:17381423)
• This study found that co-expressed cystic fibrosis transmembrane conductance regulator (CFTR) stabilizes epithelial sodium channel(ENaC) at the plasma membrane, suggesting that CFTR regulates ENaC stability, not just opening. (PMID:17434346)
• both mouse and human mammary cells express all ENaC subunits, and they are regulated by steroid hormones in a temporal and cell-specific manner both in culture and in vivo (PMID:17510235)
• genetic variants in ENaCbeta (epithelial sodium channel beta) genes do not modulate disease severity in the majority of CF patients (PMID:17560176)
• We have identified a polymorphic GT short tandem repeat, which is present in the Chilean population. Biochemical analysis showed a possible linkage between this polymorphic region and low renin hypertension. (PMID:17586416)
• alpha- & beta-hnENaC protein was increased in cystic fibrosis tissue; gamma-hnENaC was decreased; Na+ hyperabsorption not caused by hnENaC mutations, but by an increase in transcription of hnENaC subunits (PMID:17766193)
• We have shown a modest sized but highly significant effect of common genetic variation in the SCNN1B gene on plasma potassium (PMID:18184758)
• A novel point mutation in epithelial sodium channel beta subunit, causing a substitution of a leucine residue for the second proline residue of the conserved PY motif (PPP x Y) of the beta subunit was identified in the proband (PMID:18398334)
• Several variants in ENaCbeta and gamma genes might be deleterious for ENaC function and lead to bronchiectasis. (PMID:18507830)
• SCNN1B is hypermethylated in renal cell carcinoma. (PMID:18639284)
• Alpha-, beta- and gamma-ENaC messenger RNAs are detected in amiloride-sensitive BeWo trophoblast cells. (PMID:18665318)
• support a model in which protons modulate ENaC gating by relieving Na(+) self-inhibition (PMID:18990692)
• CF-like syndrome in Africa could be associated with ENaC mutations in Rwandan patients. (PMID:19017867)
• ENaC plays an important role in fluid absorption in the human endolymphatic sac and its function may be altered during inflammatory conditions. (PMID:19300301)
• A Thai family with Liddle’s syndrome caused by a novel P615H missense mutation in the proline-rich domain of the SCNN1B gene coding for the beta-subunit of ENaC. (PMID:19344079)
• Regulation of epithelial sodium channels by cGMP/PKGII. (PMID:19359370)
• Characterization of the epithelial sodium channel delta-subunit in human nasal epithelium. (PMID:19520916)
• These data together suggest that anionic phospholipids differentially regulate epithelial sodium channels (ENaCs) by physically interacting with alpha-, beta-, and gamma-ENaC subunits. (PMID:19763606)
• HOCl and its reactive intermediates (such as organic chloramines) inhibit ENaC by affecting channel gating, which could be relieved by proteases cleavage (PMID:20106988)
• SPLUNC1 potently reduced surface levels of the epithelial sodium channel (ENaC)in bronchial epithelial cells and Xenopus laevis oocytes. (PMID:20519934)
• The R563Q mutation of beta-ENaC is associated with hypertension within affected kindreds, but does not usually cause the full Liddle’s syndrome phenotype. (PMID:21107496)
• Identify the specific domains of epithelial sodium channels that are responsible for the differences in the response to flow of alphabetagamma and deltabetagamma channels. (PMID:21307123)
• heterozygous C to T mutation at codon 617 in exon 13 of SCNN1B in the proband and in all of the members of the maternal lineage submitted to genetic analysis (PMID:21525970)

Cross-species orthologs

26 orthologs

Organism	Symbol	Gene ID
mus_musculus	Scnn1b	ENSMUSG00000030873
rattus_norvegicus	Scnn1b	ENSRNOG00000030981
drosophila_melanogaster	Nach	FBGN0024319
drosophila_melanogaster	ppk28	FBGN0030795
drosophila_melanogaster	ppk17	FBGN0032602
drosophila_melanogaster	ppk6	FBGN0034489
drosophila_melanogaster	ppk12	FBGN0034730
drosophila_melanogaster	ppk29	FBGN0034965
drosophila_melanogaster	ppk24	FBGN0039839
drosophila_melanogaster	ppk22	FBGN0051105
drosophila_melanogaster	ppk8	FBGN0052792
drosophila_melanogaster	ppk5	FBGN0053289
drosophila_melanogaster	ppk16	FBGN0065108
drosophila_melanogaster	ppk11	FBGN0065109
drosophila_melanogaster	ppk9	FBGN0085398
drosophila_melanogaster	ppk18	FBGN0265001
caenorhabditis_elegans		WBGENE00003168
caenorhabditis_elegans		WBGENE00003174
caenorhabditis_elegans		WBGENE00007518
caenorhabditis_elegans		WBGENE00009073
caenorhabditis_elegans		WBGENE00011891
caenorhabditis_elegans	delm-2	WBGENE00016063
caenorhabditis_elegans	acd-1	WBGENE00016064
caenorhabditis_elegans	acd-2	WBGENE00016066
caenorhabditis_elegans		WBGENE00016699
caenorhabditis_elegans		WBGENE00017879

Paralogs (8): ASIC4 (ENSG00000072182), ASIC2 (ENSG00000108684), ASIC1 (ENSG00000110881), SCNN1A (ENSG00000111319), SCNN1D (ENSG00000162572), SCNN1G (ENSG00000166828), ASIC3 (ENSG00000213199), ASIC5 (ENSG00000256394)

Protein

Protein identifiers

Epithelial sodium channel subunit beta — P51168 (reviewed: P51168)

Alternative names: Amiloride-sensitive sodium channel subunit beta, Beta-NaCH, Nonvoltage-gated sodium channel 1 subunit beta, SCNEB

All UniProt accessions (6): A0A087WZI2, B2R812, P51168, H3BQ95, H3BRM4, H3BUQ8

UniProt curated annotations — full annotation on UniProt →

Function. This is one of the three pore-forming subunits of the heterotrimeric epithelial sodium channel (ENaC), a critical regulator of sodium balance and fluid homeostasis. ENaC operates in epithelial tissues, where it mediates the electrodiffusion of sodium ions from extracellular fluid through the apical membrane of cells, with water following osmotically. It plays a key role in maintaining sodium homeostasis through electrogenic sodium reabsorption in the kidneys. Additionally, ENaC is essential for airway surface liquid homeostasis, which is crucial for proper mucus clearance.

Subunit / interactions. Component of the heterotrimeric epithelial sodium channel (ENaC) composed of an alpha/SCNN1A, a beta/SCNN1B and a gamma/SCNN1G subunit. An additional delta/SCNN1D subunit can replace the alpha/SCNN1A subunit to form an alternative channel with specific properties. Interacts with WWP1 (via WW domains). Interacts with WWP2 (via WW domains); inhibits the channel. Interacts with the full-length immature form of PCSK9 (pro-PCSK9); inhibits ENaC by promoting its proteasomal degradation. Interacts (N-glycosylated) with BPIFA1; the interaction is direct and inhibits the proteolytic processing of SCNN1A and SCNN1G and the activation of ENaC.

Subcellular location. Apical cell membrane. Cytoplasmic vesicle membrane.

Tissue specificity. Detected in placenta, lung and kidney. Expressed in kidney (at protein level).

Post-translational modifications. Ubiquitinated. Can be ubiquitinated at multiple sites and undergo monoubiquitination and polyubiquitination. Ubiquitination by NEDD4 or NEDD4L inhibits the ENaC channel through endocytosis, intracellular retention and degradation of its individual subunits. However, some studies could not confirm the ubiquitination of this subunit of the ENaC. Phosphorylated on serine and threonine residues. Aldosterone and insulin increase the basal level of phosphorylation. N-glycosylated. N-glycosylation is required for interaction with BPIFA1.

Disease relevance. Pseudohypoaldosteronism 1B2, autosomal recessive (PHA1B2) [MIM:620125] A form of pseudohypoaldosteronism type 1, a rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. The disorder affects multiple organs, and is characterized by an often fulminant presentation in the neonatal period with dehydration, hyponatremia, hyperkalemia, metabolic acidosis, failure to thrive and weight loss. The disease is caused by variants affecting the gene represented in this entry. The degree of channel function impairment differentially affects the renin-aldosterone system and urinary Na/K ratios, resulting in distinct genotype-phenotype relationships in PHA1 patients. Loss-of-function mutations are associated with a severe clinical course and age-dependent hyperactivation of the renin-aldosterone system. This feature is not observed in patients with missense mutations that reduce but do not eliminate channel function. Markedly reduced channel activity results in impaired linear growth and delayed puberty. Liddle syndrome 1 (LIDLS1) [MIM:177200] A form of Liddle syndrome, an autosomal dominant disorder characterized by early onset of hypertension, hypokalemic alkalosis, and suppression of plasma renin activity and aldosterone secretion. The disease is caused by variants affecting the gene represented in this entry. Bronchiectasis with or without elevated sweat chloride 1 (BESC1) [MIM:211400] A debilitating respiratory disease characterized by chronic, abnormal dilatation of the bronchi and other cystic fibrosis-like symptoms in the absence of known causes of bronchiectasis (cystic fibrosis, autoimmune diseases, ciliary dyskinesia, common variable immunodeficiency, foreign body obstruction). Clinical features include sub-normal lung function, sinopulmonary infections, chronic productive cough, excessive sputum production, and elevated sweat chloride in some cases. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Originally identified and characterized by its inhibition by the diuretic drug amiloride.

Similarity. Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. SCNN1B subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P51168-1	1	yes
P51168-2	2

RefSeq proteins (2): NP_000327, NP_001397829 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001873	ENaC	Family
IPR004724	ENaC_chordates	Family
IPR020903	ENaC_CS	Conserved_site

Pfam: PF00858

Catalyzed reactions (Rhea), 1 shown:

• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (95 total): sequence variant 25, strand 21, helix 15, disulfide bond 9, turn 8, topological domain 3, sequence conflict 3, modified residue 2, transmembrane region 2, chain 1, glycosylation site 1, splice variant 1, mutagenesis site 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6WTH	ELECTRON MICROSCOPY	3.06
9BTG	ELECTRON MICROSCOPY	3.12
9BLR	ELECTRON MICROSCOPY	3.38
9BTU	ELECTRON MICROSCOPY	3.68
6BQN	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51168-F1	82.96	0.54

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 635, 633

Disulfide bonds (9): 98–272, 184–189, 196–203, 249–256, 361–448, 386–444, 390–440, 399–426, 401–415

Glycosylation sites (1): 260

Mutagenesis-validated functional residues (1):

Position	Phenotype
620	loss of inhibition of the enac channel by nedd4. loss of ubiquitination by nedd4l.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-2672351	Stimuli-sensing channels
R-HSA-9730628	Sensory perception of salty taste
R-HSA-382551	Transport of small molecules
R-HSA-9709957	Sensory Perception
R-HSA-9717189	Sensory perception of taste
R-HSA-983712	Ion channel transport

MSigDB gene sets: 351 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_ERYTHROCYTE_HOMEOSTASIS, GOBP_C21_STEROID_HORMONE_METABOLIC_PROCESS, GOBP_GROWTH, GOBP_REGULATION_OF_HORMONE_LEVELS, GOCC_CELL_SURFACE, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_RESPONSE_TO_FOOD

GO Biological Process (32): leukocyte activation involved in inflammatory response (GO:0002269), neutrophil activation involved in immune response (GO:0002283), renal system process (GO:0003014), intracellular sodium ion homeostasis (GO:0006883), regulation of blood pressure (GO:0008217), response to xenobiotic stimulus (GO:0009410), gene expression (GO:0010467), artery smooth muscle contraction (GO:0014824), response to food (GO:0032094), aldosterone metabolic process (GO:0032341), erythrocyte homeostasis (GO:0034101), multicellular organism growth (GO:0035264), sodium ion transmembrane transport (GO:0035725), epithelial fluid transport (GO:0042045), lung alveolus development (GO:0048286), multicellular organismal-level water homeostasis (GO:0050891), sensory perception of salty taste (GO:0050914), sensory perception of sour taste (GO:0050915), potassium ion homeostasis (GO:0055075), sodium ion homeostasis (GO:0055078), mucus secretion (GO:0070254), neutrophil-mediated killing of bacterium (GO:0070944), cellular response to acidic pH (GO:0071468), sodium ion import across plasma membrane (GO:0098719), cellular response to aldosterone (GO:1904045), cellular response to vasopressin (GO:1904117), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), inflammatory response (GO:0006954), blood circulation (GO:0008015), monoatomic ion transmembrane transport (GO:0034220), regulation of body fluid levels (GO:0050878)

GO Molecular Function (4): ligand-gated sodium channel activity (GO:0015280), WW domain binding (GO:0050699), sodium channel activity (GO:0005272), protein binding (GO:0005515)

GO Cellular Component (8): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), apical plasma membrane (GO:0016324), cytoplasmic vesicle membrane (GO:0030659), sodium channel complex (GO:0034706), extracellular exosome (GO:0070062), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Ion channel transport	1
Sensory perception of taste	1
Sensory Perception	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to chemical	2
sensory perception of taste	2
monoatomic cation homeostasis	2
inorganic ion homeostasis	2
inflammatory response	1
leukocyte activation	1
myeloid cell activation involved in immune response	1
immune response	1
neutrophil activation	1
system process	1
intracellular monoatomic cation homeostasis	1
sodium ion homeostasis	1
blood circulation	1
regulation of biological quality	1
macromolecule biosynthetic process	1
tonic smooth muscle contraction	1
vascular associated smooth muscle contraction	1
response to nutrient levels	1
aldehyde metabolic process	1
C21-steroid hormone metabolic process	1
mineralocorticoid metabolic process	1
primary alcohol metabolic process	1
ketone metabolic process	1
olefinic compound metabolic process	1
myeloid cell homeostasis	1
multicellular organismal process	1
developmental growth	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
fluid transport	1
transepithelial transport	1
lung development	1
anatomical structure development	1
regulation of body fluid levels	1
multicellular organismal-level chemical homeostasis	1
sodium channel activity	1
ligand-gated monoatomic cation channel activity	1
protein domain specific binding	1
monoatomic cation channel activity	1
sodium ion transmembrane transporter activity	1

Protein interactions and networks

STRING

957 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCNN1B	SCNN1G	P51170	954
SCNN1B	SCNN1A	P37088	949
SCNN1B	NEDD4	P46934	898
SCNN1B	CFTR	P13569	896
SCNN1B	NEDD4L	Q96PU5	858
SCNN1B	REN	P00797	818
SCNN1B	SLC12A3	P55017	815
SCNN1B	SGK1	O00141	802
SCNN1B	NR3C2	P08235	796
SCNN1B	WNK4	Q96J92	751
SCNN1B	KCNJ1	P48048	741
SCNN1B	SCNN1D	P51172	711
SCNN1B	WNK1	P54963	675
SCNN1B	SLC12A1	Q13621	675
SCNN1B	AQP2	P41181	622

IntAct

14 interactions, top by confidence:

A	B	Type	Score
NEDD4	SCNN1B	psi-mi:“MI:0407”(direct interaction)	0.810
SCNN1B	NEDD4	psi-mi:“MI:0407”(direct interaction)	0.810
SCNN1A	SCNN1B	psi-mi:“MI:0915”(physical association)	0.490
WWTR1	SCNN1B	psi-mi:“MI:0407”(direct interaction)	0.440
SCNN1B	NEDD4L	psi-mi:“MI:0407”(direct interaction)	0.440
COMMD1	SCNN1B	psi-mi:“MI:0915”(physical association)	0.400
SCNN1B	SCNN1B	psi-mi:“MI:0915”(physical association)	0.320

BioGRID (42): USP8 (Affinity Capture-Western), SCNN1B (Affinity Capture-Western), HGS (Affinity Capture-Western), SCNN1B (Affinity Capture-Western), SCNN1B (Affinity Capture-Western), SCNN1B (Reconstituted Complex), NEDD4 (Reconstituted Complex), SCNN1B (Reconstituted Complex), SCNN1B (Reconstituted Complex), SCNN1B (Affinity Capture-MS), NEDD4 (Far Western), NEDD4L (Far Western), HECW1 (Far Western), ITCH (Far Western), WWP2 (Far Western)

ESM2 similar proteins: A5D7U4, F1MJW3, H1AFJ5, H1AFJ6, H1AFJ7, H2LRU7, H2QAR5, H2QAR6, H9GBX2, K7FQW8, K7FSQ4, K7GET2, O13262, O13263, O35240, O62816, O70397, O97742, P24585, P24612, P34886, P37090, P37091, P49653, P51167, P51168, P51169, P51170, P51171, P78348, Q17298, Q19038, Q28738, Q60NC0, Q62765, Q62889, Q6NXK8, Q6X1Y6, Q708S3, Q708S7

Diamond homologs: A5D7U4, F1MJW3, H1AFJ5, H1AFJ6, H1AFJ7, H2Q5A1, H2QAR5, H2QAR6, H9GBX2, K7FQW8, K7FSQ4, K7GET2, O13262, O13263, O62816, O97741, O97742, P37088, P37089, P37090, P37091, P51167, P51168, P51169, P51170, P51171, P51172, P55270, Q21974, Q28738, Q61180, Q92075, Q95165, Q9R1N2, Q9W754, Q9WU38, Q9WU39, O46547, Q09274, O01635

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
SCNN1B	“up-regulates activity”	CACNA1H	binding
SCNN1B	“up-regulates quantity”	sodium(1+)	relocalization
MAPK1	“down-regulates quantity by destabilization”	SCNN1B	phosphorylation
MAPK3	“down-regulates quantity by destabilization”	SCNN1B	phosphorylation
Gbeta	“down-regulates quantity by destabilization”	SCNN1B	phosphorylation
ERK1/2	“down-regulates quantity by destabilization”	SCNN1B	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

468 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	22
Uncertain significance	237
Likely benign	81
Benign	36

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1341532	NM_000336.3(SCNN1B):c.539C>A (p.Ser180Ter)	Pathogenic
1705177	NM_000336.3(SCNN1B):c.1850C>T (p.Pro617Leu)	Pathogenic
2577438	NM_000336.3(SCNN1B):c.84G>A (p.Trp28Ter)	Pathogenic
2664487	NM_000336.3(SCNN1B):c.1271-1G>C	Pathogenic
2664488	NM_000336.3(SCNN1B):c.87C>A (p.Tyr29Ter)	Pathogenic
2664489	NM_000336.3(SCNN1B):c.1346+1G>A	Pathogenic
3338256	NM_000336.3(SCNN1B):c.1404+1G>T	Pathogenic
3772061	NM_000336.3(SCNN1B):c.831G>A (p.Trp277Ter)	Pathogenic
448298	NM_000336.3(SCNN1B):c.1747G>T (p.Glu583Ter)	Pathogenic
4528910	NM_000336.3(SCNN1B):c.101_119del (p.Asn34fs)	Pathogenic
4727224	NM_000336.3(SCNN1B):c.1394del (p.Glu465fs)	Pathogenic
8830	NM_000336.3(SCNN1B):c.1696C>T (p.Arg566Ter)	Pathogenic
8833	NM_000336.3(SCNN1B):c.1858T>C (p.Tyr620His)	Pathogenic
8834	SCNN1B, 1-BP INS, 592C	Pathogenic
8835	NM_000336.3(SCNN1B):c.1735_1766del (p.Ala579Leufs*4)	Pathogenic
8837	NM_000336.3(SCNN1B):c.1847C>G (p.Pro616Arg)	Pathogenic
8839	NM_000336.3(SCNN1B):c.1543-2A>G	Pathogenic
8841	NM_000336.3(SCNN1B):c.1615G>A (p.Glu539Lys)	Pathogenic
995266	NM_000336.3(SCNN1B):c.1854dup (p.Asn619fs)	Pathogenic
1707413	NM_000336.3(SCNN1B):c.1609C>T (p.Leu537Phe)	Likely pathogenic
2633063	NM_000336.3(SCNN1B):c.1174C>T (p.Gln392Ter)	Likely pathogenic
3061303	NM_000336.3(SCNN1B):c.720C>A (p.Tyr240Ter)	Likely pathogenic
3345984	NM_000336.3(SCNN1B):c.567del (p.Gly188_Cys189insTer)	Likely pathogenic
3579970	NM_000336.3(SCNN1B):c.653G>A (p.Trp218Ter)	Likely pathogenic
3579980	NM_000336.3(SCNN1B):c.964G>T (p.Glu322Ter)	Likely pathogenic
3579987	NM_000336.3(SCNN1B):c.1054C>T (p.Gln352Ter)	Likely pathogenic
3579989	NM_000336.3(SCNN1B):c.1074C>G (p.Tyr358Ter)	Likely pathogenic
3579991	NM_000336.3(SCNN1B):c.1212C>A (p.Tyr404Ter)	Likely pathogenic
3579992	NM_000336.3(SCNN1B):c.1228del (p.Arg410fs)	Likely pathogenic
3579997	NM_000336.3(SCNN1B):c.1314_1315del (p.Glu438fs)	Likely pathogenic

SpliceAI

2779 predictions. Top by Δscore:

Variant	Effect	Δscore
16:23302435:CAGGT:C	donor_loss	1.0000
16:23302437:GGT:G	donor_loss	1.0000
16:23302438:GTATG:G	donor_loss	1.0000
16:23302439:T:G	donor_loss	1.0000
16:23348588:GCAGG:G	acceptor_loss	1.0000
16:23348589:CAGG:C	acceptor_loss	1.0000
16:23348590:AGG:A	acceptor_loss	1.0000
16:23348911:G:GG	donor_gain	1.0000
16:23352798:CAGGT:C	acceptor_loss	1.0000
16:23352800:G:GC	acceptor_loss	1.0000
16:23353035:GATCT:G	donor_gain	1.0000
16:23353036:A:G	donor_gain	1.0000
16:23353070:GACTA:G	donor_gain	1.0000
16:23353075:G:GG	donor_gain	1.0000
16:23367956:TTCGG:T	donor_loss	1.0000
16:23367958:CGGTG:C	donor_loss	1.0000
16:23367959:GGT:G	donor_loss	1.0000
16:23367960:G:GA	donor_loss	1.0000
16:23367961:T:A	donor_loss	1.0000
16:23367962:GAG:G	donor_loss	1.0000
16:23375717:T:G	acceptor_gain	1.0000
16:23377237:GCAA:G	donor_gain	1.0000
16:23377239:AAGT:A	donor_loss	1.0000
16:23377240:AG:A	donor_loss	1.0000
16:23377241:G:GG	donor_gain	1.0000
16:23377242:T:A	donor_loss	1.0000
16:23377243:GAGT:G	donor_loss	1.0000
16:23377327:A:AG	acceptor_gain	1.0000
16:23377328:G:GA	acceptor_gain	1.0000
16:23377328:GT:G	acceptor_gain	1.0000

AlphaMissense

4251 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:23380463:T:A	W529R	0.998
16:23380463:T:C	W529R	0.998
16:23348673:T:C	L25P	0.997
16:23348753:T:A	W52R	0.997
16:23348753:T:C	W52R	0.997
16:23348883:T:A	V95D	0.997
16:23355458:T:C	C249R	0.997
16:23355460:C:G	C249W	0.997
16:23371302:T:C	L295P	0.997
16:23348709:G:A	G37D	0.996
16:23348717:C:A	R40S	0.996
16:23348798:T:A	W67R	0.996
16:23348798:T:C	W67R	0.996
16:23348874:T:G	F92C	0.996
16:23355459:G:A	C249Y	0.996
16:23380458:G:A	G527D	0.996
16:23380470:G:A	G531E	0.996
16:23380484:T:C	C536R	0.996
16:23348684:T:G	Y29D	0.995
16:23348718:G:C	R40P	0.995
16:23367895:T:G	C272W	0.995
16:23371812:T:A	C361S	0.995
16:23371813:G:C	C361S	0.995
16:23377224:T:A	C444S	0.995
16:23377225:G:C	C444S	0.995
16:23380111:T:C	L495P	0.995
16:23380431:T:C	L518P	0.995
16:23380469:G:A	G531R	0.995
16:23380469:G:C	G531R	0.995
16:23380495:G:C	E539D	0.995

dbSNP variants (sampled 300 via entrez): RS1000029263 (16:23300989 AAC>A), RS1000040461 (16:23344757 G>A), RS1000054929 (16:23326497 C>G,T), RS1000061192 (16:23360137 G>T), RS1000066077 (16:23292971 G>A), RS1000086487 (16:23299324 T>A), RS1000111681 (16:23280709 T>G), RS1000126284 (16:23314952 T>G), RS1000133439 (16:23320398 T>C), RS1000187012 (16:23336205 G>A,T), RS1000192643 (16:23346448 C>T), RS1000209319 (16:23377059 C>A,T), RS1000253634 (16:23369919 G>A), RS1000300151 (16:23355026 G>A), RS1000318749 (16:23286919 C>T)

Disease associations

OMIM: gene MIM:600760 | disease phenotypes: MIM:211400, MIM:177200, MIM:620125, MIM:264350, MIM:616026, MIM:181500, MIM:177100

GenCC curated gene-disease

Disease	Classification	Inheritance
Liddle syndrome 1	Definitive	Autosomal dominant
pseudohypoaldosteronism, type IB2, autosomal recessive	Definitive	Autosomal recessive
pseudohypoaldosteronism, type IB1, autosomal recessive	Strong	Autosomal recessive
Liddle syndrome	Supportive	Autosomal dominant
bronchiectasis with or without elevated sweat chloride 1	Limited	Semidominant

Mondo (9): bronchiectasis with or without elevated sweat chloride 1 (MONDO:0008887), Liddle syndrome 1 (MONDO:0020607), pseudohypoaldosteronism, type IB2, autosomal recessive (MONDO:0859317), pseudohypoaldosteronism, type IB1, autosomal recessive (MONDO:0009917), opsoclonus-myoclonus syndrome (MONDO:0015247), Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young (MONDO:0014458), schizophrenia (MONDO:0005090), pruritus, hereditary localized (MONDO:0008321), Liddle syndrome (MONDO:0008323)

Orphanet (7): Liddle syndrome (Orphanet:526), Idiopathic bronchiectasis (Orphanet:60033), Generalized pseudohypoaldosteronism type 1 (Orphanet:171876), Pseudohypoaldosteronism type 1 (Orphanet:756), Opsoclonus-myoclonus syndrome (Orphanet:1183), HNF1B-related autosomal dominant tubulointerstitial kidney disease (Orphanet:93111), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

61 total (30 of 61 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000112	Nephropathy
HP:0000822	Hypertension
HP:0000848	Increased circulating renin concentration
HP:0000859	Increased circulating aldosterone concentration
HP:0001047	Atopic dermatitis
HP:0001081	Cholelithiasis
HP:0001217	Clubbing
HP:0001324	Muscle weakness
HP:0001531	Failure to thrive in infancy
HP:0001658	Myocardial infarction
HP:0001824	Weight loss
HP:0001942	Metabolic acidosis
HP:0001944	Dehydration
HP:0001945	Fever
HP:0001949	Hypokalemic alkalosis
HP:0002013	Vomiting
HP:0002019	Constipation
HP:0002094	Dyspnea
HP:0002097	Emphysema
HP:0002105	Hemoptysis
HP:0002110	Bronchiectasis
HP:0002153	Hyperkalemia
HP:0002615	Hypotension
HP:0002637	Cerebral ischemia
HP:0002754	Osteomyelitis
HP:0002783	Recurrent lower respiratory tract infections
HP:0002795	Abnormal respiratory system physiology

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009598_14	Kidney stones	2.000000e-08
GCST009599_2	Kidney stones	8.000000e-06

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D056929	Liddle Syndrome	C12.050.351.968.419.815.683; C12.200.777.419.815.683; C12.950.419.815.683; C16.320.831.698
D053578	Opsoclonus-Myoclonus Syndrome	C04.588.614.550.600; C04.730.856.596; C10.228.758.500; C10.292.562.831; C10.574.781.662; C10.597.350.500.500; C11.590.725
C567618	Bronchiectasis With Or Without Elevated Sweat Chloride 1 (supp.)
C566754	Pruritus, Hereditary Localized (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1628483 (SINGLE PROTEIN), CHEMBL2107836 (PROTEIN COMPLEX)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs889299	Toxicity	3	farglitazar;glyburide	Diabetes Mellitus;Type 2

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs889299	SCNN1B	3	2.25	1	farglitazar;glyburide
rs34241435	SCNN1B		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: lgic — Epithelial sodium channel (ENaC)

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.77	IC50	17	nM	CHEMBL5303508

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Amiloride	decreases reaction, increases transport, decreases activity, affects binding	3
Sodium	affects binding, decreases reaction, increases transport, affects transport	3
sodium arsenite	affects methylation, decreases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Nickel	decreases expression	2
bisphenol F	decreases expression	1
sotorasib	affects cotreatment, decreases expression	1
propylparaben	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
lead acetate	decreases expression	1
arsenite	increases expression	1
methylparaben	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
cupric chloride	decreases expression	1
8-((4-chlorophenyl)thio)cyclic-3’,5’-GMP	increases activity, affects binding	1
8-(4-chlorophenylthio)guanosine 3’,5’-cyclic monophosphorothioate	affects binding, increases activity	1
CGP 52608	affects binding, increases reaction	1
clothianidin	increases expression	1
abrine	decreases expression	1
bisphenol S	decreases expression	1
NSC 689534	increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Arsenic Trioxide	increases expression	1
Aldosterone	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Calcitriol	increases expression	1

ChEMBL screening assays

5 unique, capped per target: 3 binding, 1 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4200635	ADMET	Inhibition of S-3969-stimulated recombinant human ENaC beta subunit expressed in HEK293 cells at 10 uM preincubated for 5 mins followed by S-3969 stimulation by FLIPR assay	6-Substituted Hexamethylene Amiloride (HMA) Derivatives as Potent and Selective Inhibitors of the Human Urokinase Plasminogen Activator for Use in Cancer. — J Med Chem
CHEMBL2051232	Binding	Inhibition of human ENaC alpha-beta-gamma expressed in Xenopus laevis oocytes assessed as effect on transmembrane currents at 1 mM by two-electrode voltage-clamp technique	Thiol-reactive compounds from garlic inhibit the epithelial sodium channel (ENaC). — Bioorg Med Chem
CHEMBL5304011	Functional	Inhibition of Na+ current by Ussing Chamber	Data for DCP probe BI-8668

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_YA79	IDG-HEK293T-SCNN1B-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

301 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety