ORF3c is a gene found in coronaviruses of the subgenus Sarbecovirus, including SARS-CoV and SARS-CoV-2. It was first identified in the SARS-CoV-2 genome and encodes a 41 amino acid non-structural protein of unknown function. ^{[1] [2] [3]} It is also present in the SARS-CoV genome, but was not recognized until the identification of the SARS-CoV-2 homolog. ^[4]

Nomenclature

There has been significant confusion in the scientific literature around the nomenclature used for the accessory proteins of SARS-CoV-2, especially several overlapping genes with ORF3a. ^[4] The predicted protein product of the ORF3c gene has at least once been referred to as "3b protein", ^[5] but it is not to be confused with the non-homologous gene ORF3b. ^[4] It has also been described under the names ORF3h ^[2] and ORF3a.iORF1. ^[6] The recommended nomenclature for SARS-CoV-2 uses the term ORF3c for this gene. ^[4]

Comparative genomics

ORF3c is an overlapping gene whose open reading frame overlaps both ORF3a and ORF3d in the SARS-CoV-2 genome. This potentially represents a rare example of all three possible reading frames of the same sequence region encoding functional proteins. ^{[7] [4]}

Bioinformatics analyses of Sarbecovirus sequences suggest that the sequence and length of ORF3c are well conserved, indicating that it is likely to encode a functional protein. ^{[1] [3] [2]} It appears to be subject to purifying selection. ^{[1] [7]}

Properties

Ribosome profiling experiments confirm that the ORF3c gene expresses a protein product. ^[6] The relatively short 41- residue protein is predicted to contain a transmembrane domain and has features suggestive of a viroporin. ^[2]

References