UniProtKB/Swiss-Prot P07686: Variant p.Arg505Gln

Beta-hexosaminidase subunit beta
Gene: HEXB
Chromosomal location: 5q13
Variant information

Variant position:  505
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 Arginine (R) to Glutamine (Q) at position 505 (R505Q, p.Arg505Gln).
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 (R) 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:  GM2-gangliosidosis 2 (GM2G2) [MIM:268800]: An autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. Clinically indistinguishable from GM2-gangliosidosis type 1, presenting startle reactions, early blindness, progressive motor and mental deterioration, macrocephaly and cherry-red spots on the macula. {ECO:0000269|PubMed:1531140, ECO:0000269|PubMed:1720305, ECO:0000269|PubMed:7557963, ECO:0000269|PubMed:7626071, ECO:0000269|PubMed:7633435, ECO:0000269|PubMed:8357844, ECO:0000269|PubMed:8950198, ECO:0000269|PubMed:9401004, ECO:0000269|PubMed:9694901, ECO:0000269|PubMed:9856491}. 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 GM2G2.
Any additional useful information about the variant.



Sequence information

Variant position:  505
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  556
The length of the canonical sequence.

Location on the sequence:   EACLWGEYVDATNLTPRLWP  R ASAVGERLWSSKDVRDMDDA
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                         EACLWGEYVDATNLTPRLWPRASAVGERLWSSKDVRDMDDA

Mouse                         EACLWGEFVDATNLTPRLWPRASAVGERLWSPKTVTDLENA

Rat                           EACLWGEYVDATNLIPRLWPRASAVGERLWSPRIITNLENA

Pig                           EACLWGEYVDATNLTPRLWPRASAVGERLWSHKDVRDIHDA

Cat                           EACLWGEFVDATNLTPRLWPRASAVGERLWSPEDITSVGNA

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 122 – 556 Beta-hexosaminidase subunit beta
Chain 315 – 556 Beta-hexosaminidase subunit beta chain A
Site 497 – 497 Not glycosylated
Helix 505 – 514


Literature citations

Molecular basis of an adult form of Sandhoff disease: substitution of glutamine for arginine at position 505 of the beta-chain of beta-hexosaminidase results in a labile enzyme.
Bolhuis P.A.; Ponne N.J.; Bikker H.; Baas F.; Vianney de Jong J.M.B.;
Biochim. Biophys. Acta 1182:142-146(1993)
Cited for: VARIANT GM2G2 GLN-505;

Significance of two point mutations present in each HEXB allele of patients with adult GM2 gangliosidosis (Sandhoff disease) homozygosity for the Ile207-->Val substitution is not associated with a clinical or biochemical phenotype.
Redonnet-Vernhet I.; Mahuran D.J.; Salvayre R.; Dubas F.; Levade T.;
Biochim. Biophys. Acta 1317:127-133(1996)
Cited for: VARIANT GM2G2 GLN-505; VARIANT VAL-207;

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.