Home  |  Contact

UniProtKB/Swiss-Prot P05186: Variant p.Cys201Tyr

Alkaline phosphatase, tissue-nonspecific isozyme
Gene: ALPL
Chromosomal location: 1p34-p36.1
Variant information

Variant position:  201
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 Cysteine (C) to Tyrosine (Y) at position 201 (C201Y, p.Cys201Tyr).
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 polar (C) to large size and aromatic (Y)
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

Involvement in disease:  Hypophosphatasia (HOPS) [MIM:146300]: A metabolic bone disease characterized by defective skeletal mineralization and biochemically by deficient activity of the tissue non-specific isoenzyme of alkaline phosphatase. Four forms are distinguished, depending on the age of onset: perinatal, infantile, childhood and adult type. The perinatal form is the most severe and is almost always fatal. The adult form is mild and characterized by recurrent fractures, osteomalacia, rickets, and loss of teeth. Some cases are asymptomatic, while some patients manifest dental features without skeletal manifestations (odontohypophosphatasia). {ECO:0000269|PubMed:10094560, ECO:0000269|PubMed:10332035, ECO:0000269|PubMed:10679946, ECO:0000269|PubMed:10690885, ECO:0000269|PubMed:10834525, ECO:0000269|PubMed:11438998, ECO:0000269|PubMed:11479741, ECO:0000269|PubMed:11745997, ECO:0000269|PubMed:11760847, ECO:0000269|PubMed:11834095, ECO:0000269|PubMed:11855933, ECO:0000269|PubMed:11999978, ECO:0000269|PubMed:12815606, ECO:0000269|PubMed:12920074, ECO:0000269|PubMed:1409720, ECO:0000269|PubMed:15135428, ECO:0000269|PubMed:15694177, ECO:0000269|PubMed:19500388, ECO:0000269|PubMed:22266140, ECO:0000269|PubMed:23039266, ECO:0000269|PubMed:23688511, ECO:0000269|PubMed:25982064, ECO:0000269|PubMed:3174660, ECO:0000269|PubMed:7833929, ECO:0000269|PubMed:8406453, ECO:0000269|PubMed:8954059, ECO:0000269|PubMed:9452105, ECO:0000269|PubMed:9747027, ECO:0000269|PubMed:9781036}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In HOPS; weak alkaline phosphatase activity; severely affects homodimerization; reduced cell surface expression.
Any additional useful information about the variant.

Sequence information

Variant position:  201
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  524
The length of the canonical sequence.

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.







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.

Chain 18 – 501 Alkaline phosphatase, tissue-nonspecific isozyme
Disulfide bond 139 – 201

Literature citations

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;

Disulfide bonds are critical for tissue-nonspecific alkaline phosphatase function revealed by analysis of mutant proteins bearing a C(201)-Y or C(489)-S substitution associated with severe hypophosphatasia.
Satou Y.; Al-Shawafi H.A.; Sultana S.; Makita S.; Sohda M.; Oda K.;
Biochim. Biophys. Acta 1822:581-588(2012)

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.