Isoform

In genetics, an isoform is a member of a set of similar products that originate from the same gene; such a set can consist of mRNAs or their resultant proteins. The best-studied isoforms are the protein isoforms, or "protein variants", resulting from differences in the coding DNA sequences (CDS) of their precursor mRNAs. While many perform the same or similar biological roles, some protein isoforms have unique functions. A set of protein isoforms may be formed from alternative splicings, variable promoter/transcription start site (TSS) usage, or other post-transcriptional modifications of a single gene; post-translational modifications are generally not considered. (For that, see Proteoforms.) Through RNA splicing mechanisms, mRNA has the ability to select different protein-coding segments (exons) of a gene, or even different parts of exons from RNA to form different mRNA sequences. Each unique sequence produces a specific form of a protein.

The discovery of isoforms could explain the discrepancy between the small number of protein coding regions of genes revealed by the Human Genome Project and the large diversity of proteins seen in an organism: different proteins encoded by the same gene could increase the diversity of the proteome. Isoforms at the protein level can manifest in the deletion of whole domains or shorter loops, usually located on the surface of the protein.

Isoforms at the RNA level are readily characterized by cDNA transcript and RNA-Seq studies. Many human genes possess confirmed alternative splicing isoforms. It has been estimated that ~100,000 expressed sequence tags (ESTs) can be identified in humans. Isoforms harboring changes in the CDS have been the most thoroughly characterized because they commonly give rise to proteins with different functional properties. RNA isoforms can differ not only in the CDS (leading to the well-known differences in resultant proteins), but also in their untranslated regions (UTRs), which regulate the levels of primary transcript in numerous ways: transcript stability, folding and turnover, as well as translation efficiency. UTRs are often the target of miRNA, which typically downregulate transcript expression by triggering degradation or halting translation. As a result, the UTR can determine how much of a transcript is translated.

In outdated usage, isoforms is also used as a vague synonym for paralogs, the products of different genes from the same organism that are related by an ancient gene duplication. For example, PRKAA1 and PRKAA2 are paralogs, but many sources simply refer to them as "isoforms".