Isoforms

Isoforms are multiple molecular forms of the same gene product. In eukaryotes, a single gene can give rise to several protein isoforms through alternative splicing of the primary transcript, the use of alternative promoters that yield different first exons, or through alternative polyadenylation that changes the transcript’s 3' end. In some cases, RNA editing can introduce nucleotide changes that alter the encoded protein sequence, producing additional transcript variants.

Protein isoforms typically differ in amino acid sequence and length, which may alter their folding, domain composition, and functional properties. They can have distinct subcellular localizations, interaction partners, stability, or enzymatic activities. Tissue-specific or developmentally regulated expression patterns frequently underlie the specialized roles of different isoforms.

Genes with multiple isoforms pose challenges for annotation and analysis. Modern sequencing approaches, including short- and long-read RNA sequencing and proteomics, help identify and validate isoforms. Public resources such as genome and proteome databases curate isoform-level information, providing transcript and protein identifiers, exon structures, and expression data.

Biological and medical relevance: isoform diversity contributes to normal physiology and development and can be altered in disease. Mis-splicing, promoter switching, or aberrant polyadenylation can disrupt normal function and contribute to cancer, neurodegeneration, and other disorders. Understanding isoform-specific expression and function supports research into diagnostics and targeted therapies. In summary, isoforms reflect the regulatory complexity that allows a single gene to produce multiple functional products.