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UniProtKB/Swiss-Prot Q3T906: Variant p.Cys505Tyr

N-acetylglucosamine-1-phosphotransferase subunits alpha/beta
Gene: GNPTAB
Chromosomal location: 12q23.3
Variant information

Variant position:  505
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
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 505 (C505Y, p.Cys505Tyr).
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:  Mucolipidosis type III complementation group A (MLIIIA) [MIM:252600]: Autosomal recessive disease of lysosomal enzyme targeting. Clinically MLIII is characterized by restricted joint mobility, skeletal dysplasia, and short stature. Mildly coarsened facial features and thickening of the skin have been described. Cardiac valvular disease and corneal clouding may also occur. Half of the reported patients show learning disabilities or mental retardation. {ECO:0000269|PubMed:16094673, ECO:0000269|PubMed:16465621, ECO:0000269|PubMed:16630736, ECO:0000269|PubMed:17034777, ECO:0000269|PubMed:19197337, ECO:0000269|PubMed:19617216, ECO:0000269|PubMed:19634183, ECO:0000269|PubMed:19938078, ECO:0000269|PubMed:23566849, ECO:0000269|PubMed:24045841, ECO:0000269|PubMed:24375680, ECO:0000269|PubMed:24550498, ECO:0000269|PubMed:25505245, ECO:0000269|PubMed:25788519, ECO:0000269|PubMed:28918368}. 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 MLIIIA; unknown pathological significance; decreased localization to the Golgi; decreased protein cleavage into alpha and beta subunits; decreased UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity; reduces protein abundance.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  505
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1256
The length of the canonical sequence.

Location on the sequence:   GSIGVGQPWQFGGGINSVSY  C NQGCANSWLADKFCDQACNV
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                         GSIGVGQPWQFGGGINSV---SYCNQGCANSWLADKFCDQACNV

Mouse                         GNIGAGQHWQFGGGINTI---SYCNQGCANSWLADKFCDQA

Zebrafish                     SVIGGGQPWQFAGGLGGLAGMSFCNQGCANSWLADKFCDQA

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 1 – 928 N-acetylglucosamine-1-phosphotransferase subunit alpha
Repeat 505 – 545 LNR 2
Metal binding 516 – 516 Calcium
Disulfide bond 505 – 528
Alternative sequence 491 – 1256 Missing. In isoform 2.


Literature citations

Analysis of mucolipidosis II/III GNPTAB missense mutations identifies domains of UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase involved in catalytic function and lysosomal enzyme recognition.
Qian Y.; van Meel E.; Flanagan-Steet H.; Yox A.; Steet R.; Kornfeld S.;
J. Biol. Chem. 290:3045-3056(2015)
Cited for: CHARACTERIZATION OF VARIANTS MLII LEU-81; ASP-182; PRO-205; LEU-334; LEU-348; LEU-374; ASN-732; ARG-928; VAL-955; CYS-986; PRO-1001; VAL-1054 AND MET-1236; CHARACTERIZATION OF VARIANTS MLIIIA GLN-4; TYR-15; VAL-190; GLN-334; PHE-399; THR-403; ALA-407; TYR-442; GLY-461; SER-468; TYR-505; PRO-587; PRO-926; TYR-956; GLY-1018 AND SER-1153; CHARACTERIZATION OF VARIANTS ARG-523; THR-592 AND TRP-785;

Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of 61 probands.
Cathey S.S.; Leroy J.G.; Wood T.; Eaves K.; Simensen R.J.; Kudo M.; Stevenson R.E.; Friez M.J.;
J. Med. Genet. 47:38-48(2010)
Cited for: VARIANTS MLIIIA GLN-4; TYR-15; VAL-190; GLN-334; PHE-399; SER-468; TYR-505; ARG-956 AND GLY-1018; VARIANT MLII LEU-348;

Mucolipidosis II and III alpha/beta in Brazil: analysis of the GNPTAB gene.
Cury G.K.; Matte U.; Artigalas O.; Alegra T.; Velho R.V.; Sperb F.; Burin M.G.; Ribeiro E.M.; Lourenco C.M.; Kim C.A.; Valadares E.R.; Galera M.F.; Acosta A.X.; Schwartz I.V.;
Gene 524:59-64(2013)
Cited for: VARIANT MLII LEU-81; VARIANTS MLIIIA PHE-399; THR-403 AND TYR-505;

Analyses of disease-related GNPTAB mutations define a novel GlcNAc-1-phosphotransferase interaction domain and an alternative site-1 protease cleavage site.
Velho R.V.; De Pace R.; Kluender S.; Sperb-Ludwig F.; Lourenco C.M.; Schwartz I.V.; Braulke T.; Pohl S.;
Hum. Mol. Genet. 24:3497-3505(2015)
Cited for: VARIANTS MLIIIA MET-644 AND THR-1223 DEL; CHARACTERIZATION OF VARIANTS MLIIIA PHE-399; THR-403; TYR-505; ARG-575; MET-644 AND THR-1223 DEL; CHARACTERIZATION OF VARIANT MLII 937-TYR--MET-972 DEL; MUTAGENESIS OF ILE-346 AND TRP-357; SUBCELLULAR LOCATION; PROTEOLYTIC CLEAVAGE;

GNPTAB missense mutations cause loss of GlcNAc-1-phosphotransferase activity in mucolipidosis type II through distinct mechanisms.
Ludwig N.F.; Velho R.V.; Sperb-Ludwig F.; Acosta A.X.; Ribeiro E.M.; Kim C.A.; Gandelman Horovitz D.D.; Boy R.; Rodovalho-Doriqui M.J.; Lourenco C.M.; Santos E.S.; Braulke T.; Pohl S.; Schwartz I.V.D.;
Int. J. Biochem. Cell Biol. 92:90-94(2017)
Cited for: VARIANTS MLII GLY-76; LEU-81; LEU-385 AND 1111-TYR--VAL-1256 DEL; CHARACTERIZATION OF VARIANTS MLII GLY-76 AND LEU-385; VARIANTS MLIIIA LEU-81; 278-GLN--VAL-1256 DEL; THR-403 AND TYR-505; FUNCTION; SUBCELLULAR LOCATION; PROTEOLYTIC PROCESSING;

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.