Exon 19 Deletion of the Platelet CD109 Gene: Characterization via Third-generation Sequencing and Structural Bioinformatics Analysis

doi:10.3969/j.issn.1671-2587.2026.04.017

JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE ›› 2026, Vol. 28 ›› Issue (4): 573-581.DOI: 10.3969/j.issn.1671-2587.2026.04.017

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Exon 19 Deletion of the Platelet CD109 Gene: Characterization via Third-generation Sequencing and Structural Bioinformatics Analysis

SONG Wenqian¹, BAI Suning², YU Wanzhen², WANG Liying¹, SHAO Linnan¹, ZHOU Shihang¹, LIANG Xiaohua¹

¹Blood Group Laboratory, Dalian Blood Center, Dalian 116001;
²College of Laboratory Medicine, Dalian Medical University, Dalian 116044

Received:2026-07-06 Online:2026-08-20 Published:2026-08-26

Abstract

Abstract: Objective To characterize the potential impacts of a CD109 exon 19 deletion on human platelet antigen 15 (HPA-15) genotyping, protein structure, and its interaction with transforming growth factor-β1 (TGF-β1). Methods A platelet donor presenting with abnormal results on routine HPA screening was enrolled. HPA-related genes were performed using third-generation sequencing on the PacBio Sequel Ⅱ platform. The effects of the variant on CD109 conformation and its binding mode to TGF-β1 were evaluated through an integrated structural bioinformatics workflow, including AlphaGenome splicing effect prediction, AlphaFold3 structural modeling, PyMOL structural superposition and alignment, and HADDOCK protein-protein docking. Functional phenotyping was complemented by blood count, coagulation assays, platelet aggregation testing, and flow cytometric analysis. Results Third-generation sequencing detected a large intragenic deletion spanning CD109 exon 19, which introduces a frameshift mutation and premature stop codon, rendering conventional HPA-15 genotyping unassignable for one haplotype. AlphaGenome analysis predicted that this structural variant may destabilize local splice site recognition and give rise to aberrant transcripts. Structural modeling demonstrated that the variant did not abrogate the overall fold of CD109, but induced localized conformational remodeling and spatial rearrangement of functional domains. Molecular docking simulations revealed altered interaction patterns at the protein-protein interface, augmented conformational heterogeneity, and a potentially dysregulated binding mode between mutant CD109 and TGF-β1. No overt abnormalities were identified on routine testings, whereas flow cytometry showed discordant expression profiles of CD42a/CD42b and CD62P/PAC-1. Conclusion The CD109 exon 19 deletion is a rare structural genomic variant that disrupts routine HPA-15 genotyping. It may drive subclinical functional perturbations in platelets by altering CD109 conformation and its interaction with TGF-β1. This study demonstrates that integrating third-generation sequencing with structural bioinformatics provides a powerful approach to unraveling the functional consequences of complex platelet antigen variants.

Key words: AlphaGenome, HPA-15, Third-generation sequencing, Molecular docking, CD109 gene

CLC Number:

R394.3

SONG Wenqian, BAI Suning, YU Wanzhen, WANG Liying, SHAO Linnan, ZHOU Shihang, LIANG Xiaohua. Exon 19 Deletion of the Platelet CD109 Gene: Characterization via Third-generation Sequencing and Structural Bioinformatics Analysis[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2026, 28(4): 573-581.

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Exon 19 Deletion of the Platelet CD109 Gene: Characterization via Third-generation Sequencing and Structural Bioinformatics Analysis

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