UniProtKB/Swiss-Prot Q9NPC4: Variant p.Gln211Glu

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

211 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 Glutamine (Q) to Glutamate (E) at position 211 (Q211E, p.Gln211Glu). 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 polar (Q) to medium size and acidic (E) 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 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 P(k) 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 individuals with NOR polyagglutination syndrome; causes the synthesis of both Gal(alpha1-4)Gal and Gal(alpha1-4)GalNAc moieties enabling the expression of P1, Pk and NOR antigens; increases catalytic efficiency. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs397514502 [ dbSNP | Ensembl ]

Sequence information Variant position:

211 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:

LDTDFIVLKNLRNLTNVLGT Q SRYVLNGAFLAFERRHEFMA 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                         LDTDFIVLKNLRNLTNVLGTQSRYVLNGAFLAFERRHEFMA

Chimpanzee                    LDTDFIVLKNLRNLTNVLGTQSRYVLNGAFLAFERRHEFMA

Mouse                         LDTDFIVLKNLLNLTNTLGIQSRYVLNGAFLAFERKHEFLA

Rat                           LDTDFIVLKNLRNLTNMLGIQSRYVLNGAFLAFERKHEFLA

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
Glycosylation	203 – 203	N-linked (GlcNAc...) asparagine
Mutagenesis	194 – 194	D -> A. Abolishes Gb3Cer/P(k) and P1 antigen expression.

Literature citations
Human Gb3/CD77 synthase reveals specificity toward two or four different acceptors depending on amino acid at position 211, creating P(k), P1 and NOR blood group antigens.
Kaczmarek R.; Duk M.; Szymczak K.; Korchagina E.; Tyborowska J.; Mikolajczyk K.; Bovin N.; Szewczyk B.; Jaskiewicz E.; Czerwinski M.;
Biochem. Biophys. Res. Commun. 470:168-174(2016)
Cited for: FUNCTION; CATALYTIC ACTIVITY; PATHWAY; CHARACTERIZATION OF VARIANT GLU-211;
Human Gb3/CD77 synthase produces P1 glycotope-capped N-glycans, which mediate Shiga toxin 1 but not Shiga toxin 2 cell entry.
Szymczak-Kulus K.; Weidler S.; Bereznicka A.; Mikolajczyk K.; Kaczmarek R.; Bednarz B.; Zhang T.; Urbaniak A.; Olczak M.; Park E.Y.; Majorczyk E.; Kapczynska K.; Lukasiewicz J.; Wuhrer M.; Unverzagt C.; Czerwinski M.;
J. Biol. Chem. 296:100299-100299(2021)
Cited for: FUNCTION; CATALYTIC ACTIVITY; PATHWAY; FUNCTION (MICROBIAL INFECTION); CHARACTERIZATION OF VARIANT GLU-211;
A single point mutation in the gene encoding Gb3/CD77 synthase causes a rare inherited polyagglutination syndrome.
Suchanowska A.; Kaczmarek R.; Duk M.; Lukasiewicz J.; Smolarek D.; Majorczyk E.; Jaskiewicz E.; Laskowska A.; Wasniowska K.; Grodecka M.; Lisowska E.; Czerwinski M.;
J. Biol. Chem. 287:38220-38230(2012)
Cited for: VARIANT GLU-211; POLYMORPHISM; FUNCTION; CATALYTIC ACTIVITY; PATHWAY; CHARACTERIZATION OF VARIANT GLU-211;

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.