FIGURE 2.

Major categories of ncORFs. Non‐canonical open reading frames are genomic regions bookended by start and stop codons, which confer the potential for translation of these genomic regions. ncORFs can exist within a variety of genomic regions including: upstream of a protein‐coding sequence (CDS) in the 5′UTR, downstream of a CDS in the 3′UTR, contained internally within a canonical CDS, overlapping by spanning from a 5′UTR into the CDS or from the CDS into the 3′UTR. Outside of annotated protein‐coding genes, ncORFs can also exist within long non‐coding RNA (lncRNA), within retroviral genes, and within pseudogenes. Finally, non‐canonical back splicing of pre‐mRNA transcripts can give rise to circular RNAs that encode unique translational products. ncORF transcription does not guarantee translation into miniproteins. However, ncORF functionality can be a product of coding‐independent activity, coding‐dependent activity, or both. Finally, cancer‐associated ncORFs, where applicable, are highlighted herein according to their classification. Figure created with biorender.com.