Fig. 1

Alignment of the human ARV1 protein with nine homologous ARV1 sequences from different metazoan species and from the slime mold Dictyostelium (Amoebozoa). Identical amino acids are marked in bold, while dashes are used to optimize the sequence alignment. The putative zinc-binding motif is boxed, while the proposed N-terminal AHD domain is underlined. Arrowheads pointing down and up mark the beginning and the end, respectively, of the six predicted transmembrane domains (TMD) [1]. The positions of the five previously reported homozygous (p.G189R, p.K59_N98del and c.674-2A>T) and compound heterozygous (p.S122Qfsstop7/p.W163stop) ARV1 variants, as well as the here-presented novel homozygous p.L185del ARV1 variant, are indicated by asterisks. Note that the splice p.K59_N98del variant results in deletion of half of the ADH domain (from K59 to N98), while the second splice c.674-2A˃T variant results in deletion of the entire C-terminal ARV1 sequence V225 downward. As indicated in the picture, all these variants were found in patients with DEE38, while four of them were found in four patients, which, in addition, also revealed DCM (see text for details). Note also that ADH and the first five predicted TMD reveal significant evolutionary conservation, while the rest of the ARV1 sequence and the last predicted TMD reveal only very limited evolutionary conservation (except the nine residues marked by the “+” characters). The sequences shown have the following GenBank accession numbers: ARV1_Hs (Homo sapiens, AAG47671.1), ARV1_Bb (Branchiostoma belcheri, XP_019640103.1), ARV1_Sk (Saccoglossus kowalevskii, XP_006817431.1), ARV1_Sp (Strongylocentrotus purpuratus, XP_787555.2), ARV1_Dm (Drosophila melanogaster, NP_730651.1), ARV1_Ce (Caenorhabditis elegans, NP_001369870.1), ARV1_Pc (Priapulus caudatus, XP_014663151.1), ARV1_Ct (Capitella teleta, ELU15651.1), ARV1_Nv (Nematostella vectensis, XP_032242188.1), ARV1_Dd (Dictyostelium discoideum, XP_635839.1).