CIC is located on the positive strand and spans approximately 27 kilobases. It has 21 exons. According to Entrez-Gene, CIC maps to NC_000019.10 of the assembly GRCh38.p2.

There are two known isoforms of CIC: short (CIC-S) and long (CIC-L). CIC-S and CIC-L have alternative transcription start sites at exon 1 and exon 0, respectively, and share exons 2-20 (Figure 1).

According to Entrez-Gene, CIC has 28 related pseudogenes.

In Drosophila and zebrafish, CIC mRNA is maternally provided to the egg (Jimenez et al. 2000; Chen et al. 2014). In zebrafish and mice, CIC mRNA is detected at various developmental stages, especially in the developing central nervous system (Lee et al. 2002; Chen et al. 2014). In adult mice, CIC mRNA is relatively highly expressed in the brain, spleen, testis, and kidney. CIC mRNA may also be expressed in the heart, lung, mammary tissue, thymus, and lymph nodes in adult mice (Lee et al. 2002).

CIC-S and CIC-L localize to both the cytoplasm and the nucleus in multiple human cell lines. CIC may also accumulate close to the mitochondria (Chittaranjan et al. 2014).

CIC has invariably been observed to act as a repressor of transcription through its DNA-binding activity. CIC has a high mobility group (HMG) box domain that confers binding to an octameric DNA motif T(G/C)AATG(A/G)A within the promoters or enhancers of its target genes (Jimenez et al. 2012). In Drosophila, presence of this octameric motif at the regulatory region of a reporter gene was necessary to confer CIC-mediated transcriptional repression, although recruitment of a corepressor protein such as Groucho may be necessary to confer repression (Ajuria et al. 2011). CICs DNA-binding activity can be inhibited through the activation (phosphorylation) of mitogen-activated protein kinase (MAPK), a core signaling molecule of receptor tyrosine kinase (RTK) pathways (Jimenez et al. 2002; Dissanayake et al. 2011). This provides a mechanism for allowing CIC target gene transcription upon RTK signaling. MAPK potentially regulates CICs transcriptionally repressive activity in three ways: through direct binding with CIC (Astigarraga et al. 2007, Futran et al. 2015), through the activation of the downstream signaling molecule p90RSK (Figure 2) to inhibit CICs DNA-binding activity (Dissanayake et al. 2011), or through influencing CICs nucleocytoplasmic shuttling (Dissanayake et al. 2011, Grimm et al. 2012). CIC levels in turn also positively regulate MAPK phosphorylation in vivo in Drosophila by protecting MAPK from phosphatases (Kim et al. 2011).
CIC functions in multiple developmental contexts in both Drosophila and mammals. For example, in Drosophila, CIC can regulate proper embryonic patterning, cell differentiation to form wing vein cells, and cell proliferation in the developing eye. In all these contexts, CIC functions in cells by restricting the expression of specific target genes when an extracellular growth signaling molecule is absent (Jimenez et al. 2002; Roch et al. 2002; Tseng et al. 2007). CIC has also been reported to function in reactive oxygen species homeostasis (Krivy et al. 2013), ATP-citrate lyase phosphorylation (Chittaranjan et al. 2014), and bile acid homeostasis (Kim et al. 2015).

CIC has homologs in mice, zebrafish, Drosophila, and C. elegans (Jimenez et al. 2000; Lee et al. 2002). Amino acid sequence identity of CICs N1 domain, HMG box domain, and C1 motif (Figure 2) is highly conserved between species (Jimenez et al 2012). This indicates that at least some of CICs biochemical functions are evolutionary conserved between animals.