UniProtKB/Swiss-Prot P37088: Variant p.Trp493Arg

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

493 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 Tryptophan (W) to Arginine (R) at position 493 (W493R, p.Trp493Arg). 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 large size and aromatic (W) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 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
Variant description:

Results in a 4-fold increase of amiloride-sensitive sodium currents; found in BESC2 patients at higher frequency than in controls; associated with an increased risk for ischemic cerebrovascular events. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs5742912 [ dbSNP | Ensembl ]

Sequence information Variant position:

493 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:

TKCRKPCSVTSYQLSAGYSR W PSVTSQEWVFQMLSRQNNYT 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                         TKCRKPCSVTSYQLSAGYSRWPSVTSQEWVFQMLSRQNNYT

Chimpanzee                    TKCRKPCSVTSYQLSAGYSRWPSVTSQEWVFQMLSRQNNYT

Mouse                         SKCRKPCSVTNYKLSAGYSRWPSVKSQDWIFEMLSLQNNYT

Rat                           SKCRKPCSVINYKLSAGYSRWPSVKSQDWIFEMLSLQNNYT

Bovine                        TKCRKPCSVTIYKLSASYSQWPSATSQDWVFQMLSRQNNYT

Rabbit                        TKCRKPCSVTNYELSAGYSRWPSVTSQDWVFQMLSLQNNYT

Chicken                       HKCRKPCKMTEYQLSAGYSRWPSAVSEDWVFYMLSQQNKYN

Xenopus laevis                TKCRKPCLVSEYQLTAGYSKWPNRVSQDWVLHTLSRQYNLT

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	107 – 562	Extracellular
Alternative sequence	246 – 669	Missing. In isoform 3.
Beta strand	478 – 494

Literature citations
Lung symptoms in pseudohypoaldosteronism type 1 are associated with deficiency of the alpha-subunit of the epithelial sodium channel.
Schaedel C.; Marthinsen L.; Kristoffersson A.-C.; Kornfalt R.; Nilsson K.O.; Orlenius B.; Holmberg L.;
J. Pediatr. 135:739-745(1999)
Cited for: VARIANT PHA1B1 LEU-562; VARIANT ARG-493; 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.