ORF10

ORF10 is an open reading frame (ORF) found in the genome of the SARS-CoV-2 coronavirus. It is 38 codons long.^[1] It is not conserved in all Sarbecoviruses (including SARS-CoV). In studies prompted by the COVID-19 pandemic, ORF10 attracted research interest as one of two viral accessory protein genes not conserved between SARS-CoV and SARS-CoV-2^[2] and was initially described as a protein-coding gene likely under positive selection.^[3] However, although it is sometimes included in lists of SARS-CoV-2 accessory genes, experimental and bioinformatics evidence suggests ORF10 is likely not a functional protein-coding gene.^[4]

ORF10 is located downstream of the N gene, which encodes coronavirus nucleocapsid protein. It is the annotated open reading frame closest to the 3' end of the genome. It encodes a 38-amino acid hypothetical protein.^[1]

It is unlikely that ORF10 is translated under natural conditions, since subgenomic RNA containing the ORF10 region is not detected, though there is some ribosome footprinting signal.^[5] When experimentally overexpressed, the ORF10 protein has been reported to interact with ZYG11B and its cullin-RING ligase protein complex.^[6] However, this interaction has been shown to be dispensable in in vitro studies of the viral life cycle.^[7]

Some studies of SARS-CoV-2 genomes have described ORF10 as likely to be functional and under positive selection.^[3] However, premature stop codons have been identified in SARS-CoV-2 variants^[8] and in many Sarbecovirus sequences, suggesting that the putative protein product is not essential for viral replication.^[4] Loss of ORF10 has also shown no effect on replication under experimental conditions in vitro.^[8] It has been suggested through bioinformatics analysis that apparent sequence conservation in SARS-CoV-2 ORF10 may not be due to a protein-coding function, but instead due to conserved RNA secondary structure in the region.^[4] The conserved region, which extends beyond ORF10 itself, overlaps with the coronavirus 3' UTR pseudoknot region, a secondary structure known to be involved in genome replication.^[4]