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UniProtKB/Swiss-Prot P54803: Variant p.Ile250Thr

Galactocerebrosidase
Gene: GALC
Variant information

Variant position:  250
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 Isoleucine (I) to Threonine (T) at position 250 (I250T, p.Ile250Thr).
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

Involvement in disease:  Leukodystrophy, globoid cell (GLD) [MIM:245200]: An autosomal recessive disorder characterized by insufficient catabolism of several galactolipids that are important for normal myelin production. Four clinical forms are recognized. The infantile form accounts for 90% of cases. It manifests before six months of age with irritability, spasticity, arrest of motor and mental development, and bouts of temperature elevation without infection. This is followed by myoclonic jerks of arms and legs, oposthotonus, hypertonic fits, and mental regression, which progresses to a severe decerebrate condition with no voluntary movements and death from respiratory infections or cerebral hyperpyrexia before 2 years of age. Cases with later onset present with unexplained blindness, weakness and sensorimotor peripheral neuropathy, mental deterioration and death. {ECO:0000269|PubMed:10234611, ECO:0000269|PubMed:10477434, ECO:0000269|PubMed:17579360, ECO:0000269|PubMed:20886637, ECO:0000269|PubMed:23462331, ECO:0000269|PubMed:8595408, ECO:0000269|PubMed:8786069, ECO:0000269|PubMed:8940268, ECO:0000269|PubMed:9272171}. 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 GLD; late infantile.
Any additional useful information about the variant.

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



Sequence information

Variant position:  250
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  685
The length of the canonical sequence.

Location on the sequence:   WESISASMLLDAELFKVVDV  I GAHYPGTHSAKDAKLTGKKL
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                         WESISASMLLDAELFKVVDVIGAHYPGTHSAKDAKLTGKKL

                              WEPISASMLLDSELLKVIDVIGAHYPGTHTVKDAKLTKKKL

Rhesus macaque                WESISAAMLLDAELFKVVDVIGAHYPGTHSVKDARLTGKKL

Mouse                         WEPISSSLLLDQELWKVVDVIGAHYPGTYTVWNAKMSGKKL

Xenopus laevis                WG-IAHDVLIDPYLNEAVQVIGAHYPGTHAAQDAIQTGKTL

Xenopus tropicalis            WQPIAFHMLQDPELLRVVDVIGAHYPGTHAAQDAILTGKTL

Zebrafish                     WS-IASAMLDDPYLNDAVEVIGVHYPGTNTVKEALLTERKL

Caenorhabditis elegans        RMDDSYSRLLDKRFINEYDIIGVHYPGGRIPENVQKSGKVI

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 43 – 685 Galactocerebrosidase


Literature citations

Molecular heterogeneity of late-onset forms of globoid-cell leukodystrophy.
De Gasperi R.; Gama Sosa M.A.; Sartorato E.L.; Battistini S.; MacFarlane H.; Gusella J.F.; Krivit W.; Kolodny E.H.;
Am. J. Hum. Genet. 59:1233-1242(1996)
Cited for: VARIANTS GLD HIS-79; SER-111; LEU-117; THR-250; SER-284 AND CYS-314; VARIANT THR-562;

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.