Seroatlas · Human Serome Atlas

SCNN1A

Epithelial sodium channel subunit alpha

Also known as: ENaCalpha, SCNN1, SCNNA_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: P37088
Gene: SCNN1A
Ensembl: ENSG00000111319
Chromosome: 12
Canonical length: 669 aa
Protein class: Disease related genes, FDA approved drug targets, Human disease related genes, Predicted membrane proteins, Transporters
Subcellular location: Vesicles,Acrosome,Annulus

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

669 residues, UniProt reviewed canonical sequence.

>P37088|SCNN1A
     1  MEGNKLEEQD SSPPQSTPGL MKGNKREEQG LGPEPAAPQQ PTAEEEALIE FHRSYRELFE
    61  FFCNNTTIHG AIRLVCSQHN RMKTAFWAVL WLCTFGMMYW QFGLLFGEYF SYPVSLNINL
   121  NSDKLVFPAV TICTLNPYRY PEIKEELEEL DRITEQTLFD LYKYSSFTTL VAGSRSRRDL
   181  RGTLPHPLQR LRVPPPPHGA RRARSVASSL RDNNPQVDWK DWKIGFQLCN QNKSDCFYQT
   241  YSSGVDAVRE WYRFHYINIL SRLPETLPSL EEDTLGNFIF ACRFNQVSCN QANYSHFHHP
   301  MYGNCYTFND KNNSNLWMSS MPGINNGLSL MLRAEQNDFI PLLSTVTGAR VMVHGQDEPA
   361  FMDDGGFNLR PGVETSISMR KETLDRLGGD YGDCTKNGSD VPVENLYPSK YTQQVCIHSC
   421  FQESMIKECG CAYIFYPRPQ NVEYCDYRKH SSWGYCYYKL QVDFSSDHLG CFTKCRKPCS
   481  VTSYQLSAGY SRWPSVTSQE WVFQMLSRQN NYTVNNKRNG VAKVNIFFKE LNYKTNSESP
   541  SVTMVTLLSN LGSQWSLWFG SSVLSVVEMA ELVFDLLVIM FLMLLRRFRS RYWSPGRGGR
   601  GAQEVASTLA SSPPSHFCPH PMSLSLSQPG PAPSPALTAP PPAYATLGPR PSPGGSAGAS
   661  SSTCPLGGP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SCNN1A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 2
Mean surface accessibility (rSASA): 0.4
Highest tissue expression: 185 nTPM

Expression across tissuesHPA

Tissue

choroid plexus: 185 nTPM
salivary gland: 150 nTPM
esophagus: 133 nTPM
kidney: 126 nTPM
thyroid gland: 88 nTPM
colon: 62 nTPM

Single-cell type

salivary duct cells: 509 nCPM
salivary ionocytes: 442 nCPM
esophageal apical cells: 425 nCPM
alveolar cells type 1: 393 nCPM
goblet cells: 372 nCPM
conjunctival goblet cells: 372 nCPM

Immune cell

neutrophil: 1.5 nTPM
plasmacytoid DC: 1 nTPM
naive CD4 T-cell: 0.5 nTPM
T-reg: 0.5 nTPM
memory CD8 T-cell: 0.2 nTPM
classical monocyte: 0.1 nTPM

Brain region

choroid plexus: 243 nTPM
hippocampal formation: 14 nTPM
thalamus: 2.8 nTPM
cerebellum: 2.3 nTPM
midbrain: 0.7 nTPM
amygdala: 0.6 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SCNN1A.

Disease | AllUniProt

Conditions SCNN1A is implicated in, by any mechanism.

Pseudohypoaldosteronism 1B1, autosomal recessive (PHA1B1) MIM:264350
Bronchiectasis with or without elevated sweat chloride 2 (BESC2) MIM:613021
Liddle syndrome 3 (LIDLS3) MIM:618126

Disease | GeneticClinVar

42 pathogenic / likely-pathogenic of 451 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Pseudohypoaldosteronism, type IB1, autosomal recessive
Bronchiectasis with or without elevated sweat chloride 2
Liddle syndrome 3
SCNN1A-related disorder
Incidental Discovery

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.91
gnomAD pLI: 0
gnomAD missense Z: -0.49
DepMap mean gene effect: -0.04
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of SCNN1A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads SCNN1A as an antibody target. Whether an autoantibody or antibody against SCNN1A could matter depends on whether native SCNN1A is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SCNN1A is annotated at the cell surface, where native SCNN1A is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label SCNN1A as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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