UniProtKB/Swiss-Prot Q9NPC4: Variant p.Pro251Leu

Lactosylceramide 4-alpha-galactosyltransferase
Gene: A4GALT
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Variant information Variant position:

251 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 Proline (P) to Leucine (L) at position 251 (P251L, p.Pro251Leu). 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 hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 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 variation in A4GALT is responsible for the P1PK system blood group phenotypes [MIM:111400]. Different combinations or absence of the P blood group system antigens define 5 different phenotypes: P1, P2, P1(k), P2(k), and p. Genetic variation in A4GALT determines the p phenotype, which is rare and does not express any antigens. It is also known as null phenotype; p individuals have antibodies against P, P1 and Pk antigens in their sera. These antibodies are clinically important because they can cause severe transfusion reactions and miscarriage (PubMed:10993874, PubMed:11896312). Genetic variation in A4GALT is also responsible for the NOR polyagglutination syndrome [MIM:111400]. Polyagglutination is the occurrence of red cell agglutination by virtually all human sera, but not by autologous serum or sera from newborns, creating a risk of complications during transfusions of NOR erythrocytes. It is caused by the unusual Gal(alpha1-4)GalNAc glycolipid epitope (PubMed:22965229). Additional information on the polymorphism described.
Variant description:

In p individuals; complete loss of activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs28940571 [ dbSNP | Ensembl ]

Sequence information Variant position:

251 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

353 The length of the canonical sequence.
Location on the sequence:

ALCMRDFVDHYNGWIWGHQG P QLLTRVFKKWCSIRSLAESR 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                         ALCMRDFVDHYNGWIWGHQGPQLLTRVFKKWCSIRSLAESR

Chimpanzee                    ALCMRDFVDHYNGWIWGHQGPQLLTRVFKKWCSIRSLAESR

Mouse                         ALCLHDFVANYNGWIWGHQGPQLLTRVFKKWCSIQSLEKSH

Rat                           ALCIRDFVAHYNGWIWGHQGPQLLTRVFKKWCSIHSLKESR

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 – 353	Lactosylceramide 4-alpha-galactosyltransferase
Topological domain	44 – 353	Lumenal

Literature citations
Molecular basis for the p phenotype. Identification of distinct and multiple mutations in the alpha 1,4-galactosyltransferase gene in Swedish and Japanese individuals.
Furukawa K.; Iwamura K.; Uchikawa M.; Sojka B.N.; Wiels J.; Okajima T.; Urano T.; Furukawa K.;
J. Biol. Chem. 275:37752-37756(2000)
Cited for: VARIANTS VAL-37; LYS-183; ASP-187 AND LEU-251; POLYMORPHISM;

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.