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UniProtKB/Swiss-Prot Q3T906: Variant p.Lys4Gln

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

Variant position:  4
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 Lysine (K) to Glutamine (Q) at position 4 (K4Q, p.Lys4Gln).
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 large size and basic (K) to medium size and polar (Q)
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

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; also found in patients with intermediate phenotype between MLII and MLIIIA; no effect on protein abundance; decreased retention in the Golgi; mistargeted to lysosomes and plasma membrane; 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.



Sequence information

Variant position:  4
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:   MLF  K LLQRQTYTCLSHRYGLYVCF
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                         MLFKLLQRQTYTCLSHRYGLYVCF

Mouse                         MLLKLLQRQTYTCLSHRYGLYVCF

Zebrafish                     SLLKLLQRQTYTCLSHRYGLYLCF

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


Literature citations

Mislocalization of phosphotransferase as a cause of mucolipidosis III alphabeta.
van Meel E.; Qian Y.; Kornfeld S.A.;
Proc. Natl. Acad. Sci. U.S.A. 111:3532-3537(2014)
Cited for: CHARACTERIZATION OF VARIANTS MLIIIA GLN-4 AND TYR-15;

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;

Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-Hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha/beta-subunits precursor gene.
Kudo M.; Brem M.S.; Canfield W.M.;
Am. J. Hum. Genet. 78:451-463(2006)
Cited for: VARIANT MLIIIA GLN-4;

Molecular analysis of cell lines from patients with mucolipidosis II and mucolipidosis III.
Zarghooni M.; Dittakavi S.S.;
Am. J. Med. Genet. A 149A:2753-2761(2009)
Cited for: VARIANTS MLII ASP-182; PRO-205; ASN-732; ARG-928; VAL-955 AND VAL-1054; VARIANT MLIIIA GLN-4; CHARACTERIZATION OF VARIANT MLIIIA GLN-4;

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;

A novel intermediate mucolipidosis II/IIIalphabeta caused by GNPTAB mutation in the cytosolic N-terminal domain.
Leroy J.G.; Sillence D.; Wood T.; Barnes J.; Lebel R.R.; Friez M.J.; Stevenson R.E.; Steet R.; Cathey S.S.;
Eur. J. Hum. Genet. 22:594-601(2014)
Cited for: VARIANT MLIIIA GLN-4; CHARACTERIZATION OF VARIANT MLIIIA GLN-4;

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.