As part of the work with APPRIS, we are investigating patterns in alternative splicing at the protein level. Since the proteins are the functional end product of coding genes, we believe that it is important to look at trends at the protein level, rather than the transcript level, where a certain amount of biological and technical noise can often obscure any signal. There is little cost associated with this noise at the transcript level, but large amounts of misfolded proteins are potentially damaging at the protein level, and will be controlled at some level, though we do not yet know the extent of this control, or the processes behind it.
However, we do know that there are numerous examples of functional alternative isoforms, and as part of our work, we will attempt to list as many as we can. List of functional isoforms that we find will be linked from this page when we find time to add them. The isoforms are also listed in the individual papers.
Note that the pairs of transcripts listed in these files are tied to a single release of Ensembl/GENCODE. The sequences or stable IDs might change in subsequent versions. Transcripts may appear in more than one list.
Functional isoforms lists we have gathered so far:
These isoforms come from this paper on tissue-specific alternative splicing:
An analysis of tissue-specific alternative splicing at the protein levelTandem exon derived substitutions involve the swapping of one (or more) coding exons for homologous coding exons. These may be at the 5' or 3' end, or be produced by mutually exclusive splicing. These transcripts produce two homologous proteins (or more) from the same gene. There are two papers detailing these isoforms:
The clinical importance of tandem exon duplication-derived substitutionsWe have merged the Ensembl/GENCODE, RefSeq and UniProtKB human reference gene sets. The initial merge was automatic based on gene name, but the merge was finalised by several rounds of manual curatcion. Genes that are not present in all three datasets or that are tagged as potential no-coding genes may not be real coding genes.
This merge was carried out with the GENCODE v45, RefSeq 110 and UniProtKB 28/3/2024 versions. Details can be found in the paper.