UniProtKB/Swiss-Prot P37088: Variant p.Thr663Ala

Amiloride-sensitive sodium channel subunit alpha
Gene: SCNN1A
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Variant information Variant position:

663 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Threonine (T) to Alanine (A) at position 663 (T663A, p.Thr663Ala). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Change from medium size and polar (T) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Other resources:

Links to websites of interest for the variant.

Variant rs2228576 [ dbSNP | Ensembl ]

Sequence information Variant position:

663 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

669 The length of the canonical sequence.
Location on the sequence:

AYATLGPRPSPGGSAGASSS T CPLGGP The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         AYATLGPR-PSPGGSAGASSSTCPL--------GGP-

Chimpanzee                    AYATLGPR-PSPGGSTGAGSSACPL--

Mouse                         AYATLGPS-ASPLDSAVPGSSACAP--

Rat                           AYATLGPS-APPLDSAAPDCSACAL--

Bovine                        AYATLGPH-PAPSGLAEASTSAHAP--

Rabbit                        AYATLGPC-LSQSG------SACAP--

Chicken                       SYNSLEPCGPSKDGETGLE--------

Xenopus laevis                AYESLDLR--SVGTLSSRSSSMRSNRS

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	1 – 669	Amiloride-sensitive sodium channel subunit alpha
Topological domain	584 – 669	Cytoplasmic
Region	620 – 669	Disordered
Alternative sequence	246 – 669	Missing. In isoform 3.

Literature citations
Upregulated expression of ENaC in human CF nasal epithelium.
Bangel N.; Dahlhoff C.; Sobczak K.; Weber W.M.; Kusche-Vihrog K.;
J. Cyst. Fibros. 7:197-205(2008)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANT ALA-663; The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
The MGC Project Team;
Genome Res. 14:2121-2127(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1); VARIANT ALA-663; Genetic variants in the epithelial sodium channel in relation to aldosterone and potassium excretion and risk for hypertension.
Ambrosius W.T.; Bloem L.J.; Zhou L.; Rebhun J.F.; Snyder P.M.; Wagner M.A.; Guo C.; Pratt J.H.;
Hypertension 34:631-637(1999)
Cited for: VARIANTS THR-334; PHE-618 AND ALA-663; Polymorphisms of amiloride-sensitive sodium channel subunits in five sporadic cases of pseudohypoaldosteronism: do they have pathologic potential?
Arai K.; Zachman K.; Shibasaki T.; Chrousos G.P.;
J. Clin. Endocrinol. Metab. 84:2434-2437(1999)
Cited for: VARIANT ALA-663; Novel mutations responsible for autosomal recessive multisystem pseudohypoaldosteronism and sequence variants in epithelial sodium channel alpha-, beta-, and gamma-subunit genes.
Saxena A.; Hanukoglu I.; Saxena D.; Thompson R.J.; Gardiner R.M.; Hanukoglu A.;
J. Clin. Endocrinol. Metab. 87:3344-3350(2002)
Cited for: VARIANT ALA-663; Impact of alphaENaC polymorphisms on the risk of ischemic cerebrovascular events: a multicenter case-control study.
Hsieh K.; Lalouschek W.; Schillinger M.; Endler G.; Reisinger M.; Janisiw M.; Lang W.; Cheng S.; Wagner O.; Mannhalter C.;
Clin. Chem. 51:952-956(2005)
Cited for: VARIANT ALA-663; ASSOCIATION OF VARIANT ARG-493 WITH RISK FOR ISCHEMIC CEREBROVASCULAR EVENTS; Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease.
Azad A.K.; Rauh R.; Vermeulen F.; Jaspers M.; Korbmacher J.; Boissier B.; Bassinet L.; Fichou Y.; des Georges M.; Stanke F.; De Boeck K.; Dupont L.; Balascakova M.; Hjelte L.; Lebecque P.; Radojkovic D.; Castellani C.; Schwartz M.; Stuhrmann M.; Schwarz M.; Skalicka V.; de Monestrol I.; Girodon E.; Ferec C.; Claustres M.; Tuemmler B.; Cassiman J.-J.; Korbmacher C.; Cuppens H.;
Hum. Mutat. 30:1093-1103(2009)
Cited for: VARIANTS BESC2 LEU-61 AND ILE-114; VARIANTS TRP-181; THR-334; ARG-493 AND ALA-663; CHARACTERIZATION OF VARIANTS BESC2 LEU-61 AND ILE-114; CHARACTERIZATION OF VARIANTS TRP-181; THR-334 AND ARG-493;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.