IIa

IIa is a designation used in molecular biology to denote a splice variant of the collagen type II alpha chain, produced from the COL2A1 gene. The IIa isoform contains exon 2 in the transcript, encoding an amino-terminal propeptide that is present in fetal forms of cartilage collagen. During vertebrate development, COL2A1 is transcribed into multiple splice variants; IIa is predominantly expressed in embryonic cartilage and developing tissues, whereas a related isoform lacking exon 2, commonly referred to as IIb (or IIB), becomes the dominant form in mature articular cartilage.

Function and expression: Type II collagen is a major structural component of the cartilage extracellular matrix. The IIa isoform is thought to participate in early cartilage formation and matrix organization, potentially influencing fibril assembly. The IIb isoform supports properties of mature cartilage as development proceeds and the tissue transitions to adult function.

Genetics and regulation: The IIa/IIb difference arises from alternative splicing of COL2A1. Regulation involves developmental cues and tissue-specific splicing factors; misregulation can affect cartilage development and extracellular matrix composition.

Clinical relevance: Alterations in COL2A1 splicing patterns, including shifts in IIa/IIb balance, have been investigated in cartilage disorders and skeletal dysplasias. Most pathogenic COL2A1 variants cause a spectrum of chondrodysplasias or Stickler-like syndromes, with disease phenotypes influenced by the overall level and timing of type II collagen expression.

See also: Type II collagen, COL2A1, cartilage.