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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P41181: Variant p.Arg254Gln

Aquaporin-2
Gene: AQP2
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Variant information Variant position: help 254 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Arginine (R) to Glutamine (Q) at position 254 (R254Q, p.Arg254Gln). 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: help Change from large size and basic (R) to medium size and polar (Q) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 1 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: help In NDI2; exerts a dominant-negative effect on wild-type-AQP2 in that it interferes with its trafficking to the apical membrane; is a loss of function instead of a gain of function mutation on dominant nephrogenic diabetes insipidus. Any additional useful information about the variant.


Sequence information Variant position: help 254 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 271 The length of the canonical sequence.
Location on the sequence: help LAVLKGLEPDTDWEEREVRR R QSVELHSPQSLPRGTKA 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         LAVLKGLEPDTDWEEREVRRRQSVELHSPQSLPRGTKA

Mouse                         LAVLKGLEPDTDWEEREVRRRQSVELHSPQSLPRGSKA

Rat                           LAVLKGLEPDTDWEEREVRRRQSVELHSPQSLPRGSKA

Bovine                        LAVLKGLEPDTDWEEREVRRRQSVELHSPQSLPRGSKA

Sheep                         LAVLKGLEPDTDWEEREVRRRQSVELHSPQSLPRGTKA
Sequence annotation in neighborhood: help 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.
TypePositionsDescription
Chain 1 – 271 Aquaporin-2
Topological domain 223 – 271 Cytoplasmic
Region 248 – 271 Disordered
Modified residue 256 – 256 Phosphoserine; by PKA
Mutagenesis 244 – 244 T -> A. No effect on sorting from the ER to the vesicles, redistribution to apical membrane, or endocytosis.
Mutagenesis 244 – 244 T -> E. No effect on sorting from the ER to the vesicles, redistribution to apical membrane, or endocytosis.
Mutagenesis 256 – 256 S -> A. Retained in vesicles.
Mutagenesis 256 – 256 S -> D. Expressed in the apical membrane.
Mutagenesis 262 – 262 P -> A. No effect on expression at the apical cell membrane.



Literature citations
p.R254Q mutation in the aquaporin-2 water channel causing dominant nephrogenic diabetes insipidus is due to a lack of arginine vasopressin-induced phosphorylation.
Savelkoul P.J.M.; De Mattia F.; Li Y.; Kamsteeg E.-J.; Konings I.B.M.; van der Sluijs P.; Deen P.M.T.;
Hum. Mutat. 30:E891-E903(2009)
Cited for: INVOLVEMENT IN NDI2; VARIANT NDI2 GLN-254; CHARACTERIZATION OF VARIANT NDI2 GLN-254;
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.