Hum Genomics 2026 Jan 13; doi: 10.1186/s40246-026-00909-y.

Naming the alpha-2-macroglobulin gene family across vertebrates.

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The HUGO Gene Nomenclature Committee (HGNC) assigns unique symbols and names to human genes and its sister project, the Vertebrate Gene Nomenclature Committee (VGNC), names genes across selected vertebrates (chimp, macaque, horse, cattle, pig, dog, cat) in line with their human orthologs. The A2M gene family, a subfamily of the thioester-containing protein (TEP) superfamily, is well conserved across vertebrates and several members of this family have already been characterized as non-specific peptidase inhibitors. Chicken ovostatin, originally termed "ovomacroglobulin", is an A2M family member that was first identified as being one of the most abundant proteins found in egg white. Two uncharacterized ovostatin homologs have also been reported in human. We wanted to assign standardized nomenclature to the multiple members of the A2M family across a wide range of vertebrate species, to capture the variation within this complex gene family. We constructed a maximum likelihood phylogenetic tree based on a multiple alignment of A2M protein sequences to help assign new nomenclature to previously unnamed A2M family genes, including the ovostatins, in human and across selected vertebrate species. This resulted in the naming of 4 human A2M family pseudogenes and 14 protein coding genes and 4 pseudogenes across VGNC species. An additional 48 genes were also named in model organisms (mouse, rat, xenopus, zebrafish, chicken) by their nomenclature committees based on this phylogenetic analysis.

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