UniProtKB/Swiss-Prot Q8IWU4: Variant p.Arg325Trp

Proton-coupled zinc antiporter SLC30A8
Gene: SLC30A8
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Variant information Variant position:

325 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 Arginine (R) to Tryptophan (W) at position 325 (R325W, p.Arg325Trp). 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 large size and aromatic (W) 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
Polymorphism:

Variant Trp-325 is a risk factor that confers susceptibility to type 2 diabetes mellitus (T2D) [MIM:125853]. Additional information on the polymorphism described.
Variant description:

Decreased transport reaction kinetics; decreased affinity for zinc ions; decreased zinc ion import into organelle; no effect on protein abundance. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs13266634 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

IWSLTMNQVILSAHVATAAS R DSQVVRREIAKALSKSFTMH 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                         IWSLTMNQVILSAHVATAASRDSQVVRREIAKALSKSFTMH

Mouse                         IWSLTVNQVILSVHVATAASQDSQSVRTGIAQALSS-FDLH

Rat                           IWSLTVNQVILSVHVATAASQDSQSVRTGIACALSSSFDLH

Xenopus laevis                LWALTMNQVILSAHIATDILGESKRILKDVTQNVCSSFPFH

Xenopus tropicalis            LWALTMNQVILSAHIATDIVGESKRILKDVTQNVFARFPFH

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 – 369	Proton-coupled zinc antiporter SLC30A8
Topological domain	267 – 369	Cytoplasmic
Binding site	318 – 318	in chain B
Binding site	345 – 345
Mutagenesis	345 – 345	H -> A. Decreased zinc ion transmembrane transport; when associated with A-137.

Literature citations
Lipid-tuned Zinc Transport Activity of Human ZnT8 Protein Correlates with Risk for Type-2 Diabetes.
Merriman C.; Huang Q.; Rutter G.A.; Fu D.;
J. Biol. Chem. 291:26950-26957(2016)
Cited for: FUNCTION; BIOPHYSICOCHEMICAL PROPERTIES; SUBUNIT; CHARACTERIZATION OF VARIANT TRP-325; A genome-wide association study identifies novel risk loci for type 2 diabetes.
Sladek R.; Rocheleau G.; Rung J.; Dina C.; Shen L.; Serre D.; Boutin P.; Vincent D.; Belisle A.; Hadjadj S.; Balkau B.; Heude B.; Charpentier G.; Hudson T.J.; Montpetit A.; Pshezhetsky A.V.; Prentki M.; Posner B.I.; Balding D.J.; Meyre D.; Polychronakos C.; Froguel P.;
Nature 445:881-885(2007)
Cited for: VARIANT TRP-325; INVOLVEMENT IN T2D;

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.