UniProtKB/SwissProt variant VAR

Variant information

Variant position:

223

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

Type of variant:

LB/B

The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Glutamate (E) to Aspartate (D) at position 223 (E223D, p.Glu223Asp).

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:

Similar physico-chemical property. Both residues are medium size and acidic.

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

2

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

Polymorphism:

Genetic variations in ABO define the ABO blood group system [MIM:616093]. The ABO blood group system is the most important blood group system in blood transfusion. The sequence shown here is that of the A transferase. The B form differs by a few residues substitution. Residues 266 and 268 are important for specificity. The reference genome assembly (GRCh38/hg38) describes a non-functional O-type ABO allele. The O-type ABO allele results in a guanine deletion (NM_020469.2: c.286delG). This deletion induces a frameshift and creates a premature stop codon resulting in a truncated (117 amino acids) protein deprived of any glycosyltransferase activity (PubMed:2333095).

Additional information on the polymorphism described.

Variant description:

In allele B106.

Any additional useful information about the variant.

Sequence information

Variant position:

223

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

Protein sequence length:

354

The length of the canonical sequence.

Location on the sequence:

EVDYLVCVDVDMEFRDHVGV E ILTPLFGTLHPGFYGSSREA

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                         EVDYLVCVDVDMEFRDHVGVEILTPLFGTLHPGFYGSSREA

Mouse                         EVDYLVCADADMKFSDHVGVEILSTFFGTLHPGFYSSSREA

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	1 – 354	Histo-blood group ABO system transferase
Chain	54 – 354	Fucosylglycoprotein alpha-N-acetylgalactosaminyltransferase soluble form
Topological domain	54 – 354	Lumenal
Binding site	211 – 211
Binding site	213 – 213
Binding site	233 – 233
Mutagenesis	214 – 214	M -> TV. Alters substrate specificity so that both UDP-N-acetyl-D-galactosamine and UDP-galactose are utilized.
Mutagenesis	234 – 234	P -> S. Alters substrate specificity of group B transferase.
Helix	222 – 224

Literature citations

Molecular genetic analysis of variant phenotypes of the ABO blood group system.
Ogasawara K.; Yabe R.; Uchikawa M.; Saitou N.; Bannai M.; Nakata K.; Takenaka M.; Fujisawa K.; Ishikawa Y.; Juji T.; Tokunaga K.;
Blood 88:2732-2737(1996)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 81-354; POLYMORPHISM; VARIANTS LEU-156; GLY-176; ARG-214; ILE-216; ASP-223; SER-235; MET-266; ALA-268; MET-277; ASN-291; GLY-352 AND TRP-352;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P16442: Variant p.Glu223Asp