UniProtKB/Swiss-Prot P06865 : Variant p.Arg504His
Beta-hexosaminidase subunit alpha Gene: HEXA
Chromosomal location: 15q23-q24
Variant information
Variant position: 504 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: Disclaimer : Variants classification is intended for research purposes only, not for clinical and diagnostic use . The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant. ]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: 504 (R504H, p.Arg504His).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: The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: 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).following page
Involvement in disease: GM2-gangliosidosis 1 (GM2G1) [MIM:272800 ]: An autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. It is characterized by GM2 gangliosides accumulation in the absence of HEXA activity, leading to neurodegeneration and, in the infantile form, death in early childhood. It exists in several forms: infantile (most common and most severe), juvenile and adult (late-onset). {ECO:0000269|PubMed:1301189 , ECO:0000269|PubMed:1301190 , ECO:0000269|PubMed:1302612 , ECO:0000269|PubMed:14566483 , ECO:0000269|PubMed:1532289 , ECO:0000269|PubMed:1837283 , ECO:0000269|PubMed:2140574 , ECO:0000269|PubMed:2144098 , ECO:0000269|PubMed:22723944 , ECO:0000269|PubMed:2522679 , ECO:0000269|PubMed:27682588 , ECO:0000269|PubMed:2970528 , ECO:0000269|PubMed:7717398 , ECO:0000269|PubMed:7837766 , ECO:0000269|PubMed:7898712 , ECO:0000269|PubMed:7951261 , ECO:0000269|PubMed:8445615 , ECO:0000269|PubMed:8490625 , ECO:0000269|PubMed:8581357 , ECO:0000269|PubMed:8757036 , ECO:0000269|PubMed:9150157 , ECO:0000269|PubMed:9338583 , ECO:0000269|PubMed:9375850 , ECO:0000269|PubMed:9401008 , ECO:0000269|PubMed:9603435 }. 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: Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.
Sequence information
Variant position: 504 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 529 The length of the canonical sequence.
Location on the sequence: R CELLRRGVQAQPLNVGFCEQ
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.
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
89 – 529 Beta-hexosaminidase subunit alpha
Alternative sequence
361 – 529 Missing. In isoform 2.
Helix
493 – 509
Literature citations
Juvenile GM2 gangliosidosis caused by substitution of histidine for arginine at position 499 or 504 of the alpha-subunit of beta-hexosaminidase.
Paw B.H.; Moskowitz S.M.; Uhrhammer N.; Wright N.; Kaback M.M.; Neufeld E.F.;
J. Biol. Chem. 265:9452-9457(1990) Cited for: VARIANT GM2G1 HIS-504; CHARACTERIZATION OF VARIANT GM2G1 HIS-504;
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.