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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

SCNN1A Gene

protein-coding GIFtS: 68
GCID: GC12M006456

sodium channel, non-voltage-gated 1 alpha subunit

(Previous names: sodium channel, nonvoltage-gated 1 alpha, sodium channel,...)
(Previous symbol: SCNN1)

Explore 38 diseases affiliated with
SCNN1A via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Sodium Channel, Non-Voltage-Gated 1 Alpha Subunit¹ ²		Alpha ENaC-2²
SCNN1¹ ² ³		Alpha-ENaC³
ENaCalpha¹ ²		Alpha-NaCH³
Sodium Channel, Nonvoltage-Gated 1 Alpha¹ ²		Amiloride-Sensitive Epithelial Sodium Channel Alpha Subunit²
Epithelial Na(+) Channel Subunit Alpha² ³		Amiloride-Sensitive Sodium Channel Subunit Alpha²
Nonvoltage-Gated Sodium Channel 1 Subunit Alpha² ³		Amiloride-Sensitive Sodium Channel Subunit Alpha 2²
SCNEA² ³		Nasal Epithelial Sodium Channel Alpha Subunit²
BESC2² ⁵		Alpha-ENaC³
Sodium Channel, Non-Voltage-Gated 1 Alpha¹		Alpha-NaCH³
ENaCa²		ENaCA³

External Ids:	HGNC: 10599¹	Entrez Gene: 6337²	Ensembl: ENSG00000111319⁷	OMIM: 600228⁵	UniProtKB: P37088³

Export aliases for SCNN1A gene to outside databases

Previous GC identifers: GC12M006310 GC12M006430 GC12M006326

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for SCNN1A:

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 alpha subunit, and mutations in this gene have been associated with pseudohypoaldosteronism type 1 (PHA1), a rare

salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. Alternatively spliced

transcript variants encoding different isoforms have been described for this gene. (provided by RefSeq, Apr 2009)

UniProtKB/Swiss-Prot: SCNNA_HUMAN, P37088

Function: Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the

electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of

epithelial cells. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in

taste perception

Gene Wiki entry for SCNN1A

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000012.11 NC_018923.1 NT_009759.16

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the SCNN1A gene promoter:
AhR GR AP-1 ATF-2 GR-beta POU3F2 Chx10 GR-alpha c-Jun NF-kappaB1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 4): SCNN1A promoter sequence

Search SABiosciences Chromatin IP Primers for SCNN1A

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat SCNN1A

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 12p13 Ensembl cytogenetic band: 12p13.31 HGNC cytogenetic band: 12p13

SCNN1A Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SCNN1A gene location

GeneLoc information about chromosome 12 GeneLoc Exon Structure

GeneLoc location for GC12M006456: view genomic region (about GC identifiers)

Start:	6,456,009 bp from pter	End:	6,486,896 bp from pter
Size:	30,888 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: SCNNA_HUMAN, P37088 (See protein sequence)

Recommended Name: Amiloride-sensitive sodium channel subunit alpha

Size: 669 amino acids; 75704 Da

Subunit: Probable heterotrimer containing one alpha, one beta and one gamma subunit. A delta subunit can replace the

alpha subunit. Interacts with the WW domains of NEDD4, NEDD4L, WWP1 and WWP2. Interacts with the full length immature

form of PCSK9 (pro-PCSK9)

Subcellular location: Apical cell membrane; Multi-pass membrane protein. Note=Apical membrane of epithelial cells

Sequence caution: Sequence=AAH06526.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;

Secondary accessions: A5X2U9 B4E2Q5 C5HTZ0 O43271 Q6GSQ6 Q9UM64

Alternative splicing: 6 isoforms: P37088-1 P37088-2 P37088-3 P37088-4 P37088-5 P37088-6 (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for SCNN1A: NX_P37088

Post-translational modifications:

Ubiquitinated; this targets individual subunits for endocytosis and proteasome-mediated degradation (By similarity)¹

ENaC cleavage by furin, and subsequently by prostasin (PRSS8), leads to a stepwise increase in the open probability of

the channel as a result of release of the alpha and gamma subunit inhibitory tracts, respectively¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P37088

SCNN1A Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (3 alternative transcripts):

NP_001029.1 NP_001153047.1 NP_001153048.1

ENSEMBL proteins:

ENSP00000353292 ENSP00000440876 ENSP00000228916 ENSP00000380166 ENSP00000345028

ENSP00000438739 ENSP00000443434 ENSP00000351825

Reactome Protein details: P37088
Human Recombinant Protein Products:

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	Browse Proteins at Uscn

Gene Ontology (GO): 5/6 cellular component terms (GO ID links to tree view) (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005624	membrane fraction	--	--
GO:0009897	external side of plasma membrane	IEA	--
GO:0016021	integral to membrane	--	--
GO:0016324	apical plasma membrane	IEA	--
GO:0030864	cortical actin cytoskeleton	IEA	--

SCNN1A for ontologies About GeneDecksing

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	Browse ELISAs and CLIAs at Uscn

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

SCNN1A for domains About GeneDecksing

3 InterPro domains/families:

IPR020903 Na+channel_ASC_CS

IPR001873 Na+channel_ASC

IPR004724 EnaC

Graphical View of Domain Structure for InterPro Entry P37088

ProtoNet protein and cluster: P37088

1 Blocks protein family: IPB001873 Na+ channel

UniProtKB/Swiss-Prot: SCNNA_HUMAN, P37088

Similarity: Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. SCNN1A subfamily

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: SCNNA_HUMAN, P37088

Function: Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the

electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of

epithelial cells. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in

taste perception

Enzyme regulation: Activated by WNK1, WNK2, WNK3 and WNK4 (By similarity)

Induction: By aldosterone

Genatlas biochemistry entry for SCNN1A:

epithelial amiloride-sensitive sodium channel,non-voltage gated in the luminal membrane of the collecting tubule of

kidney,(NHE4-PEN),subunit alpha

miRNA Products:		OriGene 3'-UTR Clone (see all 3): SCNN1A Browse MicroRNA Expression Plasmids
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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SCNN1A

Gene Ontology (GO): 5 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003779	actin binding	IEA	--
GO:0005272	sodium channel activity	--	--
GO:0005515	protein binding	IPI	--
GO:0015280	ligand-gated sodium channel activity	IEA	--
GO:0050699	WW domain binding	IPI	10642508

SCNN1A for ontologies           About GeneDecksing

Animal Models:
     Mouse knock-outs for SCNN1A: Scnn1a^tm1.2Hum Scnn1a^tm1Rss
     6 MGI mutant phenotypes (inferred from 4 alleles) (MGI details for Scnn1a):

behavior/neurological	homeostasis/metabolism	mortality/aging	normal	renal/urinary system
respiratory system

SCNN1A for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/12 super-pathways (see all 12) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Activation of cAMP-Dependent PKA

	Activation of cAMP-Dependent PKA	1.00			PKA Signaling	0.56
	cAMP Pathway	0.77

Neuropathic Pain-Signaling in Dorsal Horn Neurons

	Neuropathic Pain-Signaling in Dorsal Horn Neurons	1.00			Cholera Infection	0.40
	Aldosterone Signaling in Epithelial Cells	0.47

Ion channel transport

Ion channel transport

1.00

Stimuli-sensing channels

0.49

NO-dependent CFTR activation (normal and CF)

NO-dependent CFTR activation (normal and CF)

1.00

CFTR-dependent regulation of ion channels in Airway Epithelium (norm and CF)

CFTR-dependent regulation of ion channels in Airway Epithelium (norm and CF)

1.00

Pathway sources
See GeneCards unified pathways
Show all pathways

2 EMD Millipore Pathways for SCNN1A

	Selected targets of GCR-alpha
	Sodium channels and transporters- inward current

5/7 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for SCNN1A (see all 7)

	Cholera Infection
	Neuropathic Pain-Signaling in Dorsal Horn Neurons
	PKA Signaling
	cAMP Pathway
	Aldosterone Signaling in Epithelial Cells

2 GeneGo (Thomson Reuters) Pathways for SCNN1A

	CFTR-dependent regulation of ion channels in Airway Epithelium (norm and CF)
	NO-dependent CFTR activation (normal and CF)

3 Reactome Pathways for SCNN1A

	Transmembrane transport of small molecules
	Stimuli-sensing channels
	Ion channel transport

1 PharmGKB Pathway for SCNN1A

Diuretics Pathway, Pharmacodynamics

2 Kegg Pathways (Kegg details for SCNN1A):

	Taste transduction
	Aldosterone-regulated sodium reabsorption

SCNN1A for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for SCNN1A

STRING Interaction Network Preview (showing 5 interactants - click image to see 21)

5/21 Interacting proteins for SCNN1A (P37088^{2, 3} ENSP00000228916⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 21)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
NEDD4	P46934²^,³, ENSP00000345530⁴	MINT-14025 MINT-16750 I2D: score=4 STRING: ENSP00000345530
SNX3	O60493³, ENSP00000230085⁴	I2D: score=2 STRING: ENSP00000230085
UBE2I	P63279³, ENSP00000324897⁴	I2D: score=2 STRING: ENSP00000324897
USP10	Q14694³, ENSP00000219473⁴	I2D: score=2 STRING: ENSP00000219473
WWP2	O00308³, ENSP00000348283⁴	I2D: score=2 STRING: ENSP00000348283

About this table

Gene Ontology (GO): 5 biological process terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006814	sodium ion transport	TAS	8589714
GO:0007588	excretion	TAS	8589714
GO:0035725	sodium ion transmembrane transport	--	--
GO:0050896	response to stimulus	IEA	--
GO:0050909	sensory perception of taste	IEA	--

SCNN1A for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

SCNN1A for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for SCNN1A

2 HMDB Compounds for SCNN1A About this table

Compound	Synonyms	CAS #	PubMed Ids
Sodium	Sodium (see all 2)	7440-23-5	--
Triamterene	6-Phenyl-2,4,7-triaminopteridine (see all 25)	396-01-0	--

2 DrugBank Compounds for SCNN1A About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Triamterene	--	396-01-0	target	inhibitor	17139284 8772124 11752352 17016423 11509829
Amiloride	Amilorida [INN-Spanish] (see all 6)	2016-88-8	target	inhibitor	15084585 11752352 12928313 17556672

5 Novoseek chemical compound relationships for SCNN1A gene About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
sodium	70.4	18	10419459 (1), 19017867 (1), 8617496 (1), 10722699 (1) (see all 10)
thiazide	48.7	1	14596636 (1)
actinomycin d	41.8	2	11266509 (1)
dexamethasone	36	1	11266509 (1)
nacl	6.42	2	8617496 (1)

Search CenterWatch for drugs/clinical trials and news about SCNN1A / SCNNA

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for SCNN1A gene (3 alternative transcripts):

NM_001038.5 NM_001159575.1 NM_001159576.1

Unigene Cluster for SCNN1A:

Sodium channel, non-voltage-gated 1 alpha subunit

Hs.591047 [show with all ESTs]

Unigene Representative Sequence: AK172792

18/24 Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 24):

ENST00000360168(uc001qnw.3 uc010sfb.2) ENST00000540037(uc001qnv.3)

ENST00000228916(uc001qnx.3) ENST00000396966 ENST00000338748 ENST00000543768

ENST00000539953 ENST00000457871 ENST00000366131 ENST00000539030 ENST00000538979

ENST00000541249 ENST00000542966 ENST00000536087 ENST00000544882 ENST00000536176

ENST00000543585 ENST00000536788

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Additional cDNA sequence:

AK025536.1 AK172792.1 AK304379.1 AY365119.1 BC006526.2 BC037417.1 BC062613.1 DQ402522.1

X76180.1

20 DOTS entries:

DT.452748 DT.92434940 DT.100680671 DT.92044705 DT.100782830 DT.91967789 DT.101984086 DT.97868354

DT.95201531 DT.92434939 DT.95256681 DT.100782831 DT.121189413 DT.91688475 DT.95256668 DT.95256682

DT.121189257 DT.95256669 DT.95256679 DT.91691051

24/197 AceView cDNA sequences (see all 197):

BQ689552 AI276391 BM981737 BM839133 AI699795 AK025536 BU185396 AU099206

AI885511 AA630143 AI261669 AW247908 AU124465 NM_001038 BQ689113 BI964932

BF038512 AW080449 CD675158 AA477114 X76180 BQ690483 BC062613 BU163535

GeneLoc Exon Structure

5/12 Alternative Splicing Database (ASD) splice patterns (SP) for SCNN1A (see all 12) About this scheme

ExUns:	1	^	2a	·	2b	·	2c	^	3	^	4	^	5a	·	5b	·	5c	·	5d	·	5e	·	5f	^	6a	·	6b	·	6c	^	7	^	8	^	9	^	10	^	11	^	12	^	13	^	14	^	15	^	16	^	17	^
SP1:									-		-														-								-										-
SP2:																									-								-										-
SP3:																									-								-										-				-
SP4:																									-						-		-										-
SP5:

ExUns:	18a	·	18b
SP1:
SP2:
SP3:
SP4:
SP5:

ECgene alternative splicing isoforms for SCNN1A

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

SCNN1A expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: --

About this image

SCNN1A expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

1 LifeMap In Vivo Development Anatomical Compartment/Cell

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Kidney

Renal Collecting Duct System

Principal Cells

Kidney

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 3 LifeMap Cells

Name

Category

CyT49 (Embryonic Stem Cell)

Early Embryo, Inner Cell Mass

Matrigel embedded cells (Derivation of cardio...)

Alveolar type II cells (Derivation of mature...)

Lung

See SCNN1A Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for SCNN1A

SOURCE GeneReport for Unigene cluster: Hs.591047

UniProtKB/Swiss-Prot: SCNNA_HUMAN, P37088

Tissue specificity: Highly expressed in kidney and lung. Detected at intermediate levels in pancreas and liver, and at

low levels in heart and placenta. Isoform 1 and isoform 2 predominate in all tissues. Expression of isoform 3, isoform

4 and isoform 5 is very low or not detectable, except in lung and heart

SABiosciences Expression via Pathway-Focused PCR Array including SCNN1A:

Hypertension in human mouse rat

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In Situ
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of animals.

Orthologs for SCNN1A gene from 4/15 species (see all 15) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	SCNN1A¹	sodium channel, nonvoltage-gated 1 alpha	66.28(n) 64.61(a)		396050 NM_205145.2 NP_990476.2
lizard (Anolis carolinensis)	Reptilia	SCNN1A⁶	--	57(a)	1 ↔ 1	GL343381.1(514535-539883)
African clawed frog (Xenopus laevis)	Amphibia	alphaxENaC²	epithelial sodium channel alpha subunit	76.65(n)		U23535.1
worm (Caenorhabditis elegans)	Secernentea	unc-105³	Amiloride-sensitive sodium channel	30(a) (best of 5)		II(8117189-8122268) --

ENSEMBL Gene Tree for SCNN1A (if available)
TreeFam Gene Tree for SCNN1A (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for SCNN1A gene

SCNN1B² ASIC3² SCNN1G² ASIC4² SCNN1D² ASIC5² ASIC2² ASIC1²

3 SIMAP similar genes for SCNN1A using alignment to 9 protein entries: SCNNA_HUMAN (see all proteins):

SCNN1D SCNN1G SCNN1B

SCNN1A for paralogs About GeneDecksing

1 Pseudogenes.org Pseudogene for SCNN1A
PGOHUM00000258611

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
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SNP ID	Valid	Clinical significance	Chr 12 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs5742912^1,2	C,F,H,	pathogenic	6458350(-)	`CACGAT/CGGCCC`	6	/R /W	mis¹		19		NS NA EA EU	9866
rs193920773^1,2	C,	unknown	6464452(-)	`CCTCCA/GTCAGC`	6	I V	mis¹		0	--	--	--	--
rs11608320^1,2	C,F,H	--	6455548(+)	`TGAGCC/ATCATC`	3	--	ds500¹		5		NS EA NA	420
rs11608322^1,2	C,F,H,	--	6455576(+)	`GACAGA/C/TTGATG`	3	--	ds500¹		7		NS EA NA	552
rs72657528^1,2	C,	--	6455609(+)	`ATTGCC/TGCCAG`	3	--	ds500¹		1		NS	1118
rs139766401^1,2		--	6455698(+)	`GAGGTC/TCAGAC`	3	--	ds500¹		0	--	--	--	--
rs114278043^1,2		--	6455701(+)	`GTTCAG/TACAGT`	3	--	ds500¹		1		WA	118
rs144357613^1,2		--	6455737(+)	`TGTGAA/GGTAGG`	3	--	ds500¹		0	--	--	--	--
rs187528632^1,2		--	6455809(+)	`GCAGAC/TGCTCA`	3	--	ds500¹		0	--	--	--	--
rs62622412^1,2	C,F,	--	6455960(+)	`GACTTG/ATATCC`	3	--	ds500¹		2		NS NA	1114

HapMap Linkage Disequilibrium report for SCNN1A (6456009 - 6486896 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 3 variations for SCNN1A
2 CNVs: 3872 8705
1 Indel: 101414
Human Gene Mutation Database (HGMD): SCNN1A

Locus Specific Mutation Databases (LSDB): SCNN1A

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

SCNN1A for disorders           About GeneDecksing

OMIM gene information: 600228
OMIM disorders: 264350  613021
UniProtKB/Swiss-Prot: SCNNA_HUMAN, P37088

Defects in SCNN1A are a cause of pseudohypoaldosteronism 1, autosomal recessive (PHA1B) [MIM:264350]. 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. Note=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 (PubMed:18634878)

Defects in SCNN1A are a cause of bronchiectasis with or without elevated sweat chloride type 2 (BESC2)

[MIM:613021]; also called cystic fibrosis-like syndrome. BESC2 is 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 subnormal lung function, sinopulmonary infections, chronic productive

cough, excessive sputum production, and elevated sweat chloride in some cases

20/38 diseases for SCNN1A (see all 38): About MalaCards

pseudohypoaldosteronism bronchiectasis with or without elevated sweat chloride 2 autosomal recessive pseudohypoaldosteronism type 1 pseudohypoaldosteronism type i

endolymphatic hydrops pseudohypoaldosteronism type ii common variable immunodeficiency ciliary dyskinesia

liddle syndrome delayed puberty amyotrophic lateral sclerosis lateral sclerosis

bronchiectasis familial hypercholesterolemia chronic lymphocytic leukemia cerebral palsy

pulmonary edema respiratory failure lymphocytic leukemia hypercholesterolemia

3 diseases from the University of Copenhagen DISEASES database for SCNN1A:

Pseudohypoaldosteronism Liddle syndrome Hypertension

2 Novoseek disease relationships for SCNN1A gene About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
pseudohypoaldosteronism	91.5	3	20064610 (1), 12530930 (1), 16207733 (1)
liddles syndrome	87.9	3	20064610 (1), 12530930 (1), 16207733 (1)

Genetic Association Database (GAD): SCNN1A
Human Genome Epidemiology (HuGE) Navigator: SCNN1A (35 documents)

Export disorders for SCNN1A gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for SCNN1A gene, integrated from 9 sources (see all 184):
(articles sorted by number of sources associating them with SCNN1A)

Utopia: connect your pdf to the dynamic
world of online information

The alpha-subunit of the epithelial sodium channel is an aldosterone- induced transcript in mammalian collecting ducts, and this transcriptional response is mediated via distinct cis-elements in the 5'-flanking region of the gene. (PubMed id 11266509)^{1, 2, 9} Mick V.E....Thomas C.P. (2001)
Hormonal regulation and genomic organization of the human amiloride- sensitive epithelial sodium channel alpha subunit gene. (PubMed id 10447117)^{1, 2, 9} Chow Y.H.... Hu J. (1999)
Cloning and functional studies of splice variants of the alpha- subunit of the amiloride-sensitive Na+ channel. (PubMed id 9575806)^{1, 2, 9} Tucker J.K.... Oh Y. (1998)
Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease. (PubMed id 19462466)^{1, 2} Azad A.K.... Cuppens H. (2009)
Renin-aldosterone response, urinary Na/K ratio and growth in pseudohypoaldosteronism patients with mutations in epithelial sodium channel (ENaC) subunit genes. (PubMed id 18634878)^{1, 2} Hanukoglu A....Hanukoglu I. (2008)
Upregulated expression of ENaC in human CF nasal epithelium. (PubMed id 17766193)^{1, 2} Bangel N....Kusche-Vihrog K. (2008)
Novel mutations in epithelial sodium channel (ENaC) subunit genes and phenotypic expression of multisystem pseudohypoaldosteronism. (PubMed id 15853823)^{1, 2} Edelheit O.... Hanukoglu A. (2005)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S....Malek J. (2004)
Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel. (PubMed id 11696533)^{1, 2} Snyder P.M.... Thomas B.C. (2002)
Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na(+) channel. (PubMed id 12167593)^{1, 2} McDonald F.J....Snyder P.M. (2002)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 6337	HGNC: 10599	AceView: SCNN1A	Ensembl:ENSG00000111319	euGenes: HUgn6337
ECgene: SCNN1A	Kegg: 6337	H-InvDB: SCNN1A

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for SCNN1A	Pharmacogenomics, SNPs, Pathways
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SCNN1A

Intellectual Property for SCNN1A gene
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Patent Information for SCNN1A gene:
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SCNN1A Gene

sodium channel, non-voltage-gated 1 alpha subunit

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SCNN1A (Gene Symbol)
Sodium Channel, Non-Voltage-Gated 1 Alpha Subunit
SCNN1
ENaCalpha
Sodium Channel, Nonvoltage-Gated 1 Alpha
Epithelial Na(+) Channel Subunit Alpha
Nonvoltage-Gated Sodium Channel 1 Subunit Alpha
SCNEA
BESC2
Sodium Channel, Non-Voltage-Gated 1 Alpha
ENaCa
Alpha ENaC-2
Alpha-ENaC
Alpha-NaCH
Amiloride-Sensitive Epithelial Sodium Channel Alpha Subunit
Amiloride-Sensitive Sodium Channel Subunit Alpha
Amiloride-Sensitive Sodium Channel Subunit Alpha 2
Nasal Epithelial Sodium Channel Alpha Subunit
Alpha-ENaC
Alpha-NaCH
ENaCA

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SCNN1A Gene

sodium channel, non-voltage-gated 1 alpha subunit

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