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UniProtKB/Swiss-Prot Q13563: Variant p.Trp414Gly

Polycystin-2
Gene: PKD2
Chromosomal location: 4q21-q23
Variant information

Variant position:  414
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Tryptophan (W) to Glycine (G) at position 414 (W414G, p.Trp414Gly).
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 glycine (G)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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

Involvement in disease:  Polycystic kidney disease 2 (PKD2) [MIM:613095]: A disorder characterized by progressive formation and enlargement of cysts in both kidneys, typically leading to end-stage renal disease in adult life. Cysts also occurs in the liver and other organs. It represents approximately 15% of the cases of autosomal dominant polycystic kidney disease. PKD2 is clinically milder than PKD1 but it has a deleterious impact on overall life expectancy. {ECO:0000269|PubMed:10411676, ECO:0000269|PubMed:10541293, ECO:0000269|PubMed:10835625, ECO:0000269|PubMed:11854751, ECO:0000269|PubMed:11968093, ECO:0000269|PubMed:12707387, ECO:0000269|PubMed:14993477, ECO:0000269|PubMed:15772804, ECO:0000269|PubMed:21115670, ECO:0000269|PubMed:27071085, ECO:0000269|PubMed:9326320}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In PKD2; affects channel activity as it is able to abolish channel currents induced by the gain-of-function artificial mutant P-604.
Any additional useful information about the variant.



Sequence information

Variant position:  414
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  968
The length of the canonical sequence.

Location on the sequence:   DLSRTREETAAQVASLKKNV  W LDRGTRATFIDFSVYNANIN
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                         DLSRT-REETAAQVASLKKNVWLDRGTRATFIDFSV-----YNANIN

Mouse                         DLSRT-REETAAQLAGLRRNFWLDRGTRAAFIDFSV-----

Bovine                        DLSRT-REETAAQVANLKKNVWLDRGTRAIFIDFTV-----

Zebrafish                     DLSRT-REKSANQLQELKNNLWLDRGTRAVFLDFSI-----

Caenorhabditis elegans        RLPVAGSTEAQSAIATLKANRWIDRGSRAIIVDFAL-----

Fission yeast                 DLGSL-AKRATTTVTTSTSDSITLRGIKRISYMMGIETTNF

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.

TypePositionsDescription
Chain 1 – 968 Polycystin-2
Topological domain 242 – 468 Extracellular


Literature citations

Function and regulation of TRPP2 ion channel revealed by a gain-of-function mutant.
Arif Pavel M.; Lv C.; Ng C.; Yang L.; Kashyap P.; Lam C.; Valentino V.; Fung H.Y.; Campbell T.; Moeller S.G.; Zenisek D.; Holtzman N.G.; Yu Y.;
Proc. Natl. Acad. Sci. U.S.A. 113:E2363-E2372(2016)
Cited for: FUNCTION; SUBCELLULAR LOCATION; MUTAGENESIS OF PHE-604; PHE-605 AND 736-LEU-ASN-737; CHARACTERIZATION OF VARIANTS PKD2 GLY-414; GLY-420 AND VAL-511;

A spectrum of mutations in the second gene for autosomal dominant polycystic kidney disease (PKD2).
Veldhuisen B.; Saris J.J.; de Haij S.; Hayashi T.; Reynolds D.M.; Mochizuki T.; Elles R.; Fossdal R.; Bogdanova N.; van Dijk M.A.; Coto E.; Ravine D.; Noerby S.; Verellen-Dumoulin C.; Breuning M.H.; Somlo S.; Peters D.J.M.;
Am. J. Hum. Genet. 61:547-555(1997)
Cited for: VARIANT PKD2 GLY-414;

Genotype-renal function correlation in type 2 autosomal dominant polycystic kidney disease.
Magistroni R.; He N.; Wang K.; Andrew R.; Johnson A.; Gabow P.; Dicks E.; Parfrey P.; Torra R.; San-Millan J.L.; Coto E.; Van Dijk M.; Breuning M.; Peters D.; Bogdanova N.; Ligabue G.; Albertazzi A.; Hateboer N.; Demetriou K.; Pierides A.; Deltas C.; St George-Hyslop P.; Ravine D.; Pei Y.;
J. Am. Soc. Nephrol. 14:1164-1174(2003)
Cited for: VARIANTS PKD2 PRO-356; GLY-414; ARG-632 AND GLN-807;

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.