KIAA1549 Antibody #79092

KIAA1549 is a multi-pass membrane protein primarily expressed in the central nervous system and enriched in the connecting cilium of photoreceptors (1). The human KIAA1549 gene consists of 20 exons, with an alternate promoter within intron 8 and a variable splicing site within intron 19, yielding two short and two long isoforms (1,2). The long isoform is primarily expressed in brain tissue, and the short isoform is almost exclusively expressed in retina (1). While the endogenous function of KIAA1549 protein is still not well understood, homozygous mutations in the short KIAA1549 isoform have been observed in retinitis pigmentosa patients (1). Aberrant tandem duplications in chromosomal region 7q34 cause the expression of a novel fusion protein, combining the KIAA1549 N-terminus with the B-Raf C-terminus (2,3). The most common fusion observed is between KIAA1549 exons 1-16 and BRAF exons 9-18, though additional fusion combinations have been observed (2-4). KIAA1549::B-Raf fusion proteins are the primary drivers of low-grade juvenile pilocytic astrocytomas, the most common glioma in children (2,3). Because the inhibitory N-terminal regions of B-Raf protein are missing in these fusion proteins, unregulated downstream MEK/Erk signaling drives tumor growth (4-6). KIAA1549::B-Raf tumors have demonstrated resistance to several type 1 B-Raf inhibitors, though second-generation B-Raf inhibitors and clinical inhibitors of MEK1/2 have shown promise (7-9).