UniProtKB/Swiss-Prot Q92508: Variant p.Arg2456His

Piezo-type mechanosensitive ion channel component 1
Gene: PIEZO1
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Variant information Variant position:

2456 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LP/P [Disclaimer] 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 Arginine (R) to Histidine (H) at position 2456 (R2456H, p.Arg2456His). 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 basic (R) to medium size and polar (H) 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
Variant description:

In DHS1; gives rise to mechanically activated currents that inactivate more slowly than wild-type currents. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs587776988 [ dbSNP | Ensembl ]

Sequence information Variant position:

2456 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

2521 The length of the canonical sequence.
Location on the sequence:

AGYGIMGLYVSIVLVIGKFV R GFFSEISHSIMFEELPCVDR 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                         AGYGIMGLYVSIVLVIGK-FVRGFFSEISHSIMFEELPCVDR

Mouse                         AGYGIVGLYVSIVLVVGK-FVRGFFSEISHSIMFEELPCVD

Rat                           AGYGIVGLYVSIVLVVGK-FVRGFFSDISHSIMFEELPCVD

Caenorhabditis elegans        FKGGVIAVYLSVILVVGRGLVRGIFTTSPSTVMFTELPNAD

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 – 2521	Piezo-type mechanosensitive ion channel component 1
Mutagenesis	2456 – 2456	R -> K. Does not inactivate the protein. gives rise to mechanically activated currents that inactivate more slowly than wild-type currents, suggesting it could shift the channel kinetics from phasic to tonic.

Literature citations
Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis.
Zarychanski R.; Schulz V.P.; Houston B.L.; Maksimova Y.; Houston D.S.; Smith B.; Rinehart J.; Gallagher P.G.;
Blood 120:1908-1915(2012)
Cited for: PROTEIN SEQUENCE OF 955-972; 1324-1334; 1548-1562 AND 1656-1671; VARIANTS DHS1 ARG-2225 AND HIS-2456; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1.
Andolfo I.; Alper S.L.; De Franceschi L.; Auriemma C.; Russo R.; De Falco L.; Vallefuoco F.; Esposito M.R.; Vandorpe D.H.; Shmukler B.E.; Narayan R.; Montanaro D.; D'Armiento M.; Vetro A.; Limongelli I.; Zuffardi O.; Glader B.E.; Schrier S.L.; Brugnara C.; Stewart G.W.; Delaunay J.; Iolascon A.;
Blood 121:3925-3935(2013)
Cited for: VARIANTS DHS1 SER-718; SER-782; GLN-808; LEU-1117; ASP-2003; VAL-2020; MET-2127; 2166-LYS--LYS-2169 DEL; HIS-2456 AND GLN-2488; CHARACTERIZATION OF VARIANTS DHS1 HIS-2456 AND GLN-2488; FUNCTION; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; DEVELOPMENTAL STAGE; Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels.
Albuisson J.; Murthy S.E.; Bandell M.; Coste B.; Louis-Dit-Picard H.; Mathur J.; Feneant-Thibault M.; Tertian G.; de Jaureguiberry J.P.; Syfuss P.Y.; Cahalan S.; Garcon L.; Toutain F.; Simon Rohrlich P.; Delaunay J.; Picard V.; Jeunemaitre X.; Patapoutian A.;
Nat. Commun. 4:1884-1884(2013)
Cited for: VARIANTS DHS1 PRO-1358; THR-2020; MET-2127 AND LEU-GLU-2496 INS; CHARACTERIZATION OF VARIANTS DHS1 PRO-1358; THR-2020; MET-2127; LEU-GLU-2496 INS; ARG-2225 AND HIS-2456; FUNCTION; SUBCELLULAR LOCATION; Xerocytosis is caused by mutations that alter the kinetics of the mechanosensitive channel PIEZO1.
Bae C.; Gnanasambandam R.; Nicolai C.; Sachs F.; Gottlieb P.A.;
Proc. Natl. Acad. Sci. U.S.A. 110:E1162-1168(2013)
Cited for: VARIANTS DHS1 ARG-2225 AND HIS-2456; CHARACTERIZATION OF VARIANTS DHS1 ARG-2225 AND HIS-2456; MUTAGENESIS OF ARG-2456; Dehydrated stomatocytic anemia due to the heterozygous mutation R2456H in the mechanosensitive cation channel PIEZO1: a case report.
Shmukler B.E.; Vandorpe D.H.; Rivera A.; Auerbach M.; Brugnara C.; Alper S.L.;
Blood Cells Mol. Dis. 52:53-54(2014)
Cited for: VARIANT DHS1 HIS-2456; Recurrent mutation in the PIEZO1 gene in two families of hereditary xerocytosis with fetal hydrops.
Beneteau C.; Thierry G.; Blesson S.; Le Vaillant C.; Picard V.; Bene M.C.; Eveillard M.; Le Caignec C.;
Clin. Genet. 85:293-295(2014)
Cited for: VARIANT DHS1 HIS-2456;

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.