UniProtKB/Swiss-Prot P05186: Variant p.Arg223Trp

Alkaline phosphatase, tissue-nonspecific isozyme
Gene: ALPL
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Variant information Variant position:

223 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 Arginine (R) to Tryptophan (W) at position 223 (R223W, p.Arg223Trp). 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 HOPS and HPPC; severe allele; abolished alkaline phosphatase activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs766076920 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

DIAYQLMHNIRDIDVIMGGG R KYMYPKNKTDVEYESDEKAR 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                         DIAYQLMHNIRDIDVIMGGGRKYMYPKNKTDVEYESDEKAR

Mouse                         DIAYQLMHNIKDIDVIMGGGRKYMYPKNRTDVEYELDEKAR

Rat                           DIAYQLMHNIKDIDVIMGGGRKYMYPKNRTDVEYELDEKAR

Bovine                        DIAYQLMHNIKDIEVIMGGGRKYMFPKNRTDVEYELDEKAR

Cat                           DIAYQLMHNVRDIEVIMGGGRKYMFPKNRTDVEYEMDEKAR

Chicken                       DIARQLVDNIPDIEVILGGGRKYMFPKNTSDVEYPQEERHR

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	18 – 501	Alkaline phosphatase, tissue-nonspecific isozyme
Binding site	235 – 235
Glycosylation	230 – 230	N-linked (GlcNAc...) asparagine
Mutagenesis	235 – 235	E -> A. Abolished alkaline phosphatase activity.

Literature citations
Identification of fifteen novel mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in European patients with severe hypophosphatasia.
Mornet E.; Taillandier A.; Peyramaure S.; Kaper F.; Muller F.; Brenner R.; Bussiere P.; Freisinger P.; Godard J.; Le Merrer M.; Oury J.F.; Plauchu H.; Puddu R.; Rival J.M.; Superti-Furga A.; Touraine R.L.; Serre J.L.; Simon-Bouy B.;
Eur. J. Hum. Genet. 6:308-314(1998)
Cited for: VARIANTS HOPS PHE-17; VAL-40; SER-75; ARG-120; ARG-129; ASP-170; TRP-184; LYS-191; TRP-223; LYS-291; ASP-334; PRO-445; CYS-450; SER-473 AND ARG-491; VARIANT HIS-263; Correlations of genotype and phenotype in hypophosphatasia.
Zurutuza L.; Muller F.; Gibrat J.F.; Taillandier A.; Simon-Bouy B.; Serre J.L.; Mornet E.;
Hum. Mol. Genet. 8:1039-1046(1999)
Cited for: VARIANTS HOPS VAL-40; LEU-62; SER-75; THR-111; ARG-120; ARG-129; HIS-136; VAL-162; ASP-170; TYR-171; TRP-184; LYS-191; TRP-223; VAL-249; LYS-291; VAL-306; ASP-334; CYS-391; PRO-445; CYS-450; SER-473; LYS-476 AND ARG-491; 3D-STRUCTURE MODELING; CHARACTERIZATION OF VARIANTS; A molecular approach to dominance in hypophosphatasia.
Lia-Baldini A.S.; Muller F.; Taillandier A.; Gibrat J.F.; Mouchard M.; Robin B.; Simon-Bouy B.; Serre J.L.; Aylsworth A.S.; Bieth E.; Delanote S.; Freisinger P.; Hu J.C.-C.; Krohn H.-P.; Nunes M.E.; Mornet E.;
Hum. Genet. 109:99-108(2001)
Cited for: CHARACTERIZATION OF VARIANTS HOPS VAL-40; VAL-63; THR-116; LEU-181; TRP-184; TRP-223; VAL-249; VAL-378; ILE-478 AND PHE-490; Mutational analysis and functional correlation with phenotype in German patients with childhood-type hypophosphatasia.
Orimo H.; Girschick H.J.; Goseki-Sone M.; Ito M.; Oda K.; Shimada T.;
J. Bone Miner. Res. 16:2313-2319(2001)
Cited for: INVOLVEMENT IN HPPC; VARIANTS HPPC MET-68; SER-71; THR-177; TRP-223; PRO-275 AND HIS-391; CHARACTERIZATION OF VARIANTS HPPC MET-68; SER-71; THR-177; TRP-223; PRO-275 AND HIS-391; VARIANT ALA-522; CHARACTERIZATION OF VARIANT ALA-522; Kinetic characterization of hypophosphatasia mutations with physiological substrates.
Di Mauro S.; Manes T.; Hessle L.; Kozlenkov A.; Pizauro J.M.; Hoylaerts M.F.; Millan J.L.;
J. Bone Miner. Res. 17:1383-1391(2002)
Cited for: VARIANTS HOPS VAL-33; CYS-71; PRO-71; THR-111; VAL-132; THR-177; THR-179; GLY-191; LYS-191; TRP-223; ALA-294; ASP-334; VAL-378; ILE-382 AND ARG-456; VARIANT HPPI LYS-298; CHARACTERIZATION OF VARIANTS HOPS VAL-33; CYS-71; PRO-71; THR-111; VAL-132; THR-177; THR-179; GLY-191; LYS-191; TRP-223; ALA-294; ASP-334; VAL-378; ILE-382 AND ARG-456; CHARACTERIZATION OF VARIANT HPPI LYS-298; FUNCTION; CATALYTIC ACTIVITY; Denaturing gradient gel electrophoresis analysis of the tissue nonspecific alkaline phosphatase isoenzyme gene in hypophosphatasia.
Mumm S.; Jones J.; Finnegan P.; Henthorn P.S.; Podgornik M.N.; Whyte M.P.;
Mol. Genet. Metab. 75:143-153(2002)
Cited for: VARIANTS HOPS SER-51; HIS-71; THR-111; MET-128; HIS-134; HIS-136; THR-176; LYS-191; GLN-223; TRP-223; SER-246; ALA-294; PRO-299; PHE-327 DEL; ARG-339; THR-348; VAL-378; MET-414; ASP-426 AND LYS-476; VARIANTS HIS-263 AND ALA-522; Characterization of 11 novel mutations in the tissue non-specific alkaline phosphatase gene responsible for hypophosphatasia and genotype-phenotype correlations.
Brun-Heath I.; Taillandier A.; Serre J.-L.; Mornet E.;
Mol. Genet. Metab. 84:273-277(2005)
Cited for: VARIANTS HOPS VAL-33; HIS-136; GLN-223; TRP-223; HIS-272; THR-292; ALA-294; THR-295; ASP-297; ASP-334 AND ALA-411; CHARACTERIZATION OF VARIANTS HOPS VAL-33; HIS-272; THR-292; THR-295; ASP-297 AND ALA-411;

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.