UniProtKB/Swiss-Prot Q3T906: Variant p.Ile403Thr

N-acetylglucosamine-1-phosphotransferase subunits alpha/beta
Gene: GNPTAB
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Variant information Variant position:

403 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 Isoleucine (I) to Threonine (T) at position 403 (I403T, p.Ile403Thr). 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 hydrophobic (I) to medium size and polar (T) 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 MLIIIA; loss of localization to the Golgi; loss of protein cleavage into alpha and beta subunits; decreased UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs281864973 [ dbSNP | Ensembl ]

Sequence information Variant position:

403 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:

FSSPAIESHIHRIEGLSQKF I YLNDDVMFGKDVWPDDFYSH 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                         FSSPAIESHIHRIEGLSQKFIYLNDDVMFGKDVWPDDFYSH

Mouse                         FSSPAIESHIHRIEGLSQKFIYLNDDVMFGKDVWPDDFYSH

Zebrafish                     FSSPAIETHIHRIPGLSQKFIYLNDDVMFGKDVWPDDFYSH

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	1 – 928	N-acetylglucosamine-1-phosphotransferase subunit alpha
Beta strand	400 – 405

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; Molecular characterization of 22 novel UDP-N-acetylglucosamine-1-phosphate transferase alpha- and beta-subunit (GNPTAB) gene mutations causing mucolipidosis types IIalpha/beta and IIIalpha/beta in 46 patients.
Tappino B.; Chuzhanova N.A.; Regis S.; Dardis A.; Corsolini F.; Stroppiano M.; Tonoli E.; Beccari T.; Rosano C.; Mucha J.; Blanco M.; Szlago M.; Di Rocco M.; Cooper D.N.; Filocamo M.;
Hum. Mutat. 30:E956-E973(2009)
Cited for: VARIANTS MLIIIA THR-403; TYR-442; GLY-461 AND PRO-926; VARIANT MLII PRO-1001; 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.