Identification of a novel A allele with a missense mutation (c.737A&gt;G) in a Chinese individual with a weak A phenotype

He, Baoren; Li, Bin; Liu, Jinlian; Liu, Xuejun

doi:10.1111/trf.15929

Cited by 2 publications

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References 2 publications

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“…Based on structural topology analysis, the residue 246 was located in the vicinity of the catalytic active sites of the GTB enzyme. The other two variants ABO*A allele with c.737A > G were found by other researchers [18,19]. Both of the variants were suggested to may alter the catalytic function of the protein.…”

Section: Discussionmentioning

confidence: 72%

Mechanism evaluation for an amino acid substitution p.Y246C of B‐glycosyltransferase enzyme with Bweak phenotype

Ying

Hong

et al. 2020

Vox Sanguinis

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Background The amino acid substitutions caused by ABO gene variants are usually predicted to impact the glycosyltransferase function. Here, the effect of an amino acid substitution in the vicinity of the catalytic active region of the B‐glycosyltransferase was explored in vitro and in silico study, which is important for further recognizing the ABO subgroup. Methods The ABO serological tests were performed by the routine methods. The ABO genotype was analyzed by polymerase chain reaction and sequenced bidirectionally. The haplotype of the variant allele was separated using single‐strand amplification and sequencing with allele‐specific primers. Stably expression cell lines with variant were constructed for study in vitro. 3D structure of the B‐glycosyltransferase (GTB) variant was simulated by PyMOL software. The free energy change (ΔΔG) was calculated by FoldX. Results A variant c.737A > G was identified in a Chinese individual with Bweak phenotype, which led to an amino acid substitution p.Y246C in the vicinity of the catalytic active region of GTB enzyme. The stably expression cell lines with variant and wild type were successfully established and showed that the variant caused a decrease in protein levels and/or enzyme activity. The 3D structural of the GTB modelling found the amino acid substitution p.Y246C caused the hydrogen bond of the protein changes. Meanwhile, the free energy change (ΔΔG) value predicted the destabilizing effect on the variant GTB. Discussion The p.Y246C variant in the vicinity of the enzyme active centre reduced the antigen expression because of greatly destabilizing effect on the GTB variant.

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Section: Discussionmentioning

confidence: 72%

Mechanism evaluation for an amino acid substitution p.Y246C of B‐glycosyltransferase enzyme with Bweak phenotype

Ying

Hong

et al. 2020

Vox Sanguinis

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Serological and molecular characterization of novel ABO variants including an interesting B(A) subgroup

He,

Yu,

Zhang

et al. 2024

Transfusion

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BackgroundABO grouping is the most important pretransfusion testing that is directly related to the safety of blood transfusion. A weak ABO subgroup is one of the important causes of an ABO grouping discrepancy. Here, we investigated the characterization of four novel ABO variants including a novel B(A) subgroup.Study Design and MethodsRBCs were phenotyped by standard serology methods. The full coding regions of the ABO gene and the erythroid cell‐specific regulatory elements in intron one were sequenced. The effect of the possible splice site variant was predicted by Alamut software. The 3D structural modeling of three relative B(A) enzymes (p.Met214Thr, p.Met214Val, and p.Met214Leu) were performed by PyMOL software.ResultsFour novel ABO alleles were identified with weak ABO expression in this study, in which two would lead to premature terminations, and two resulted in amino acid changes. In silico analysis revealed that the splice site variant c.155G>T had the potential to alter splice transcripts. 3D structural view shown that the variant amino acid position 214 was spatially adjacent to the donor recognition pocket residues (266Met and 268Ala) and just next to the 211DVD213 motif. The size of the side chain of Thr and Val is the smallest, Leu is medium, and Met is the largest, and the size changes in the critical position 214 may affect the donor recognition pocket.ConclusionFour ABO subgroup alleles were newly linked to different kinds of ABO variants and the possible mechanism through which they produce weak ABO subgroups was analyzed in silico.

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Identification of a novel A allele with a missense mutation (c.737A>G) in a Chinese individual with a weak A phenotype

Cited by 2 publications

References 2 publications

Mechanism evaluation for an amino acid substitution p.Y246C of B‐glycosyltransferase enzyme with Bweak phenotype

Mechanism evaluation for an amino acid substitution p.Y246C of B‐glycosyltransferase enzyme with Bweak phenotype

Serological and molecular characterization of novel ABO variants including an interesting B(A) subgroup

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