UniProtKB/Swiss-Prot P05186: Variant p.Glu191Lys

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

191 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 Glutamate (E) to Lysine (K) at position 191 (E191K, p.Glu191Lys). 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 medium size and acidic (E) to large size and basic (K) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

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:

In HOPS; moderate; frequent mutation in European countries; slightly reduced alkaline phosphatase activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121918007 [ dbSNP | Ensembl ]

Sequence information Variant position:

191 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:

HATPSAAYAHSADRDWYSDN E MPPEALSQGCKDIAYQLMHN 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                         HATPSAAYAHSADRDWYSDNEMPPEALSQGCKDIAYQLMHN

Mouse                         HATPSAAYAHSADRDWYSDNEMPPEALSQGCKDIAYQLMHN

Rat                           HATPSAAYAHSADRDWYSDNEMPPEALSQGCKDIAYQLMHN

Bovine                        HATPSASYAHSADRDWYSDNEMPPEALSQGCKDIAYQLMHN

Cat                           HATPSAAYAHSADRDWYSDNEMPPEALSQGCKDIAYQLMHN

Chicken                       HATPSAAYAHSANRDWYSDGEMPLDALEGGCKDIARQLVDN

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	173 – 173
Disulfide bond	139 – 201
Turn	189 – 191

Literature citations
Different missense mutations at the tissue-nonspecific alkaline phosphatase gene locus in autosomal recessively inherited forms of mild and severe hypophosphatasia.
Henthorn P.S.; Raducha M.; Fedde K.N.; Lafferty M.A.; Whyte M.P.;
Proc. Natl. Acad. Sci. U.S.A. 89:9924-9928(1992)
Cited for: VARIANTS HOPS VAL-33; CYS-71; PRO-71; LYS-191; PRO-207; ALA-294; VAL-378 AND HIS-436; VARIANT HIS-263; 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; Characterization of eleven novel mutations (M45L, R119H, 544delG, G145V, H154Y, C184Y, D289V, 862+5A, 1172delC, R411X, E459K) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with severe hypophosphatasia.
Taillandier A.; Zurutuza L.; Muller F.; Simon-Bouy B.; Serre J.L.; Bird L.; Brenner R.; Boute O.; Cousin J.; Gaillard D.; Heidemann P.H.; Steinmann B.; Wallot M.; Mornet E.;
Hum. Mutat. 13:171-172(1999)
Cited for: VARIANTS HOPS LEU-62; HIS-136; VAL-162; TYR-171; LYS-191; TYR-201; VAL-249; VAL-306 AND LYS-476; Fifteen new mutations (-195C>T, L-12X, 298-2A>G, T117N, A159T, R229S, 997+2T>A, E274X, A331T, H364R, D389G, 1256delC, R433H, N461I, C472S) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with hypophosphatasia.
Taillandier A.; Cozien E.; Muller F.; Merrien Y.; Bonnin E.; Fribourg C.; Simon-Bouy B.; Serre J.L.; Bieth E.; Brenner R.; Cordier M.P.; De Bie S.; Fellmann F.; Freisinger P.; Hesse V.; Hennekam R.C.M.; Josifova D.; Kerzin-Storrar L.; Leporrier N.; Zabot M.-T.; Mornet E.;
Hum. Mutat. 15:293-293(2000)
Cited for: VARIANTS HOPS VAL-40; THR-111; ASN-134; THR-176; LYS-191; TYR-201; SER-246; THR-348; ARG-381; GLY-406; HIS-450; ILE-478 AND SER-489; Twelve novel mutations in the tissue-nonspecific alkaline phosphatase gene (ALPL) in patients with various forms of hypophosphatasia.
Taillandier A.; Lia-Baldini A.S.; Mouchard M.; Robin B.; Muller F.; Simon-Bouy B.; Serre J.L.; Bera-Louville A.; Bonduelle M.; Eckhardt J.; Gaillard D.; Myhre A.G.; Koertge-Jung S.; Larget-Piet L.; Malou E.; Sillence D.; Temple I.K.; Viot G.; Mornet E.;
Hum. Mutat. 18:83-84(2001)
Cited for: VARIANTS HPPI CYS-28 AND MET-459; VARIANTS HOPS VAL-40; VAL-51; HIS-71; THR-116; HIS-136; HIS-152; THR-176; THR-179; LYS-191; ASP-211; VAL-220; GLY-235; TYR-294; GLY-327; SER-399 AND ALA-423; 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; Mild forms of hypophosphatasia mostly result from dominant negative effect of severe alleles or from compound heterozygosity for severe and moderate alleles.
Fauvert D.; Brun-Heath I.; Lia-Baldini A.S.; Bellazi L.; Taillandier A.; Serre J.L.; de Mazancourt P.; Mornet E.;
BMC Med. Genet. 10:51-51(2009)
Cited for: VARIANTS HOPS CYS-71; HIS-71; THR-111; THR-176; LYS-191; ARG-334; ASP-334; ARG-339; ILE-382; CYS-391; HIS-391; MET-414; ALA-420; LYS-452; LEU-459 AND ALA-476; CHARACTERIZATION OF VARIANTS HOPS CYS-71; HIS-71; THR-111; THR-176; LYS-191; ARG-334; ASP-334; ARG-339; ILE-382; CYS-391; HIS-391; MET-414; LYS-452; LEU-459 AND ALA-476;

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.