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UniProtKB/Swiss-Prot P05186: Variant p.Leu414Met

Alkaline phosphatase, tissue-nonspecific isozyme
Gene: ALPL
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 Leucine (L) to Methionine (M) at position 414 (L414M, p.Leu414Met).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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

Variant description:  In HOPS; loss of alkaline phosphatase activity.
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:  524
The length of the canonical sequence.

Location on the sequence:   SIFGLAPMLSDTDKKPFTAI  L YGNGPGYKVVGGERENVSMV
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                         SIFGLAPMLSDTDKKPFTAILYGNGPGYKVVGGERENVSMV

Mouse                         SIFGLAPMVSDTDKKPFTAILYGNGPGYKVVDGERENVSMV

Rat                           SIFGLAPMVSDTDKKPFTAILYGNGPGYKVVDGERENVSMV

Bovine                        SIFGLAPMVSDTDKKPFTAILYGNGPGYKVVGGERENVSMV

Cat                           SIFGLAPMVSDTDKKPFTSILYGNGPGYKVVGGERENVSMV

Chicken                       PIFGLAPMQSDVDRKPFTSILYGNGPGYKIVGGERENVSAV

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 18 – 501 Alkaline phosphatase, tissue-nonspecific isozyme
Glycosylation 430 – 430 N-linked (GlcNAc...) asparagine


Literature citations

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;

Molecular study of three cases of odontohypophosphatasia resulting from heterozygosity for mutations in the tissue non-specific alkaline phosphatase gene.
Herasse M.; Spentchian M.; Taillandier A.; Keppler-Noreuil K.; Fliorito A.N.M.; Bergoffen J.; Wallerstein R.; Muti C.; Simon-Bouy B.; Mornet E.;
J. Med. Genet. 40:605-609(2003)
Cited for: VARIANTS HOPS LEU-108; THR-116 AND MET-414; CHARACTERIZATION OF VARIANT HOPS LEU-108;

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.