UniProtKB/Swiss-Prot Q6P5W5: Variant p.Arg251Trp

Zinc transporter ZIP4
Gene: SLC39A4
Feedback?

Variant information Variant position:

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

US 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 251 (R251W, p.Arg251Trp). 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
Variant description:

In AEZ; uncertain significance. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs2977838 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

LGVGREAHSDHSHRHRGASS R DPVPLISSSNSSSVWDTVCL 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                         LGVGREAHS---------DHSHRHRGASSRDPVPLISSSNSSSVWDTVCL

Mouse                         LGVGGEDHSDHDDHGDHADHSHPDRKASHQDSELHTPHNSN

Rat                           LGVGGEDHS---DHGDHVDHSHLDREANHQDSELHATHNSS

Bovine                        LGLGGATEP----HDSHSDDSPLGKG---QGPVPLAAPNSS

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	23 – 647	Zinc transporter ZIP4
Topological domain	23 – 327	Extracellular
Region	236 – 255	Disordered
Glycosylation	261 – 261	N-linked (GlcNAc...) asparagine
Mutagenesis	238 – 238	H -> S. Decreases zinc transport activity; when associated with S-241; S-243; S-245. Decreases Vmax for Zn(2+) by 20% but does not affect the KM; when associated with S-241; S-243; S-245.
Mutagenesis	241 – 241	H -> S. Decreases zinc transport activity; when associated with S-238; S-243 and S-245. Decreases Vmax for Zn(2+) by 20% does not affect the KM; when associated with S-238; S-243 and S-245.
Mutagenesis	243 – 243	H -> S. Decreases zinc transport activity; when associated with S-238; S-241 and S-245. Decreases Vmax for Zn(2+) by 20% does not affect the KM; when associated with S-238; S-241 and S-245.
Mutagenesis	245 – 245	H -> S. Decreases zinc transport activity; when associated with S-238; S-241 and S-243. Decreases Vmax for Zn(2+) by 20% but does not affect the KM; when associated with S-238; S-241 and S-243.
Mutagenesis	261 – 261	N -> Q. Decreases location at cell membrane; retained in the ER.
Mutagenesis	266 – 266	W -> A. No glycosylated. Very low cell surface expression. Decreases zinc uptake activity.

Literature citations
DNA sequence and analysis of human chromosome 8.
Nusbaum C.; Mikkelsen T.S.; Zody M.C.; Asakawa S.; Taudien S.; Garber M.; Kodira C.D.; Schueler M.G.; Shimizu A.; Whittaker C.A.; Chang J.L.; Cuomo C.A.; Dewar K.; FitzGerald M.G.; Yang X.; Allen N.R.; Anderson S.; Asakawa T.; Blechschmidt K.; Bloom T.; Borowsky M.L.; Butler J.; Cook A.; Corum B.; DeArellano K.; DeCaprio D.; Dooley K.T.; Dorris L. III; Engels R.; Gloeckner G.; Hafez N.; Hagopian D.S.; Hall J.L.; Ishikawa S.K.; Jaffe D.B.; Kamat A.; Kudoh J.; Lehmann R.; Lokitsang T.; Macdonald P.; Major J.E.; Matthews C.D.; Mauceli E.; Menzel U.; Mihalev A.H.; Minoshima S.; Murayama Y.; Naylor J.W.; Nicol R.; Nguyen C.; O'Leary S.B.; O'Neill K.; Parker S.C.J.; Polley A.; Raymond C.K.; Reichwald K.; Rodriguez J.; Sasaki T.; Schilhabel M.; Siddiqui R.; Smith C.L.; Sneddon T.P.; Talamas J.A.; Tenzin P.; Topham K.; Venkataraman V.; Wen G.; Yamazaki S.; Young S.K.; Zeng Q.; Zimmer A.R.; Rosenthal A.; Birren B.W.; Platzer M.; Shimizu N.; Lander E.S.;
Nature 439:331-335(2006)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]; VARIANT TRP-251; A novel member of a zinc transporter family is defective in acrodermatitis enteropathica.
Wang K.; Zhou B.; Kuo Y.-M.; Zemansky J.; Gitschier J.;
Am. J. Hum. Genet. 71:66-73(2002)
Cited for: TISSUE SPECIFICITY; VARIANTS THR-58; LEU-84; THR-114 AND ALA-357; VARIANTS AEZ LYS-106; TRP-251; TYR-309; ASP-330; PRO-372; PRO-410 AND ARG-630;

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.