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UniProtKB/Swiss-Prot P34059: Variant p.Thr235Lys

N-acetylgalactosamine-6-sulfatase
Gene: GALNS
Chromosomal location: 16q24.3
Variant information

Variant position:  235
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 Threonine (T) to Lysine (K) at position 235 (T235K, p.Thr235Lys).
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 (T) to large size and basic (K)
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:  Mucopolysaccharidosis 4A (MPS4A) [MIM:253000]: A form of mucopolysaccharidosis type 4, an autosomal recessive lysosomal storage disease characterized by intracellular accumulation of keratan sulfate and chondroitin-6-sulfate. Key clinical features include short stature, skeletal dysplasia, dental anomalies, and corneal clouding. Intelligence is normal and there is no direct central nervous system involvement, although the skeletal changes may result in neurologic complications. There is variable severity, but patients with the severe phenotype usually do not survive past the second or third decade of life. {ECO:0000269|PubMed:1522213, ECO:0000269|PubMed:16287098, ECO:0000269|PubMed:24726177, ECO:0000269|PubMed:7581409, ECO:0000269|PubMed:7633425, ECO:0000269|PubMed:7668283, ECO:0000269|PubMed:7795586, ECO:0000269|PubMed:8651279, ECO:0000269|PubMed:8826435, ECO:0000269|PubMed:9298823, ECO:0000269|PubMed:9375852, ECO:0000269|PubMed:9521421}. 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 MPS4A.
Any additional useful information about the variant.

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



Sequence information

Variant position:  235
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  522
The length of the canonical sequence.

Location on the sequence:   DFIKRQARHHPFFLYWAVDA  T HAPVYASKPFLGTSQRGRYG
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                         DFIKRQ-ARHHPFFLYWAVDATHAPVYASKPFLGTSQRGRYG

                              DFIKRQQAAQRPFFLYWAIDATHAPVYASRPFLGTSQRGRY

Mouse                         DFIQTQHARQSPFFLYWAIDATHAPVYASRQFLGTSLRGRY

Rat                           DFIRTQHARQSPFFLYWAIDATHAPVYASKQFLGTSLRGRY

Pig                           DFIKRQQATHHPFFLYWAIDATHAPVYASRAFLGTSQRGRY

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 27 – 522 N-acetylgalactosamine-6-sulfatase
Region 27 – 379 Catalytic domain


Literature citations

Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations.
Morrone A.; Tylee K.L.; Al-Sayed M.; Brusius-Facchin A.C.; Caciotti A.; Church H.J.; Coll M.J.; Davidson K.; Fietz M.J.; Gort L.; Hegde M.; Kubaski F.; Lacerda L.; Laranjeira F.; Leistner-Segal S.; Mooney S.; Pajares S.; Pollard L.; Ribeiro I.; Wang R.Y.; Miller N.;
Mol. Genet. Metab. 112:160-170(2014)
Cited for: VARIANTS MPS4A GLU-16; ARG-36; ASN-40; GLY-48; LYS-51; ARG-77; LEU-80; LEU-81; GLU-84; TRP-90; PRO-91; CYS-94; LEU-94; PHE-113; VAL-116; SER-116; SER-139; ARG-141; TYR-145; LEU-151; ARG-155; LEU-156; ARG-166; SER-179; GLU-201; PRO-214; SER-216; GLY-230; ASN-233; LYS-235; THR-264; LEU-287; THR-291; CYS-301; SER-312; ARG-318; LEU-357; GLY-380; THR-380; CYS-386; HIS-386; VAL-391; VAL-392; HIS-407; VAL-415; THR-416; ARG-420; THR-492; VAL-494; SER-500 AND PHE-507; VARIANTS PHE-74; ASP-121; CYS-159; TYR-165; GLN-251; CYS-254; LYS-260 AND LYS-495; CHARACTERIZATION OF VARIANTS MPS4A GLU-16; ARG-36; LYS-51; LEU-81; GLU-84; PRO-91; VAL-116; TYR-145; LEU-156; ARG-166; GLU-201; PRO-214; SER-216; THR-264; GLY-380; VAL-415; THR-416; ARG-420; THR-492 AND SER-500;

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.