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UniProtKB/Swiss-Prot P51795: Variant p.Cys291Arg

H(+)/Cl(-) exchange transporter 5
Gene: CLCN5
Variant information

Variant position:  291
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 Cysteine (C) to Arginine (R) at position 291 (C291R, p.Cys291Arg).
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 (C) 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:  In NPHL2; retained in the endoplasmic reticulum; improperly N-glycosylated and non-functional.
Any additional useful information about the variant.

Sequence information

Variant position:  291
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  816
The length of the canonical sequence.

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.






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.

Chain 1 – 816 H(+)/Cl(-) exchange transporter 5
Transmembrane 281 – 300 Helical
Site 281 – 281 Mediates proton transfer from the outer aqueous phase to the interior of the protein; involved in linking H(+) and Cl(-) transport
Mutagenesis 281 – 281 E -> A. Abolishes proton transport, but not chloride transport.

Literature citations

Evidence for genetic heterogeneity in Dent's disease.
Hoopes R.R. Jr.; Raja K.M.; Koich A.; Hueber P.; Reid R.; Knohl S.J.; Scheinman S.J.;
Kidney Int. 65:1615-1620(2004)
Cited for: VARIANTS NPHL2 ARG-291; LEU-314; ALA-337; GLY-340; ASP-532; ARG-583; TRP-586; ASN-615; GLU-616 AND SER-727;

Novel CLCN5 mutations in patients with Dent's disease result in altered ion currents or impaired exchanger processing.
Grand T.; Mordasini D.; L'Hoste S.; Pennaforte T.; Genete M.; Biyeyeme M.J.; Vargas-Poussou R.; Blanchard A.; Teulon J.; Lourdel S.;
Kidney Int. 76:999-1005(2009)
Cited for: VARIANTS NPHL2 ASP-249; LEU-273; ALA-282 AND PRO-539; CHARACTERIZATION OF VARIANTS NPHL2 ASP-249; ARG-270; LEU-273; ALA-282; ARG-289; ARG-291 AND PRO-539;

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.