The gene spans 5608 bp containing 5 exons of which 2 (exons 3 and 4) are protein-encoding.

The ID2 gene has 4 transcripts, of which 3 can generate functional protein: ID2-001 (2041bp) contains all 5 exons, ID2-201 (1362 bp) contains 3 exons and ID2-002 contains 2 exons. ID2-003 (474 bp) contains a retained intron.

A pseudogene of ID2 is located on chromosome 3.

ID2 belongs to the helix-loop-helix (HLH) protein family. It is composed by 134 aa and belongs to a subgroup HLH family members (ID1, ID2, ID3, ID4) that lack a basic DNA-binding domain. ID proteins form heterodimers with class I basic HLH-group members such as MyoD (Langlands et al., 1997), NEDD9 (Law et al., 1999), and E2A gene products E12 and E47. ID2 has a main domain located on 38-79 aa responsible for the helix-loop-helix conformation. In addition, Id2 contains a 10 aa motif that is responsible for the nuclear export signaling.

Expression of ID2 is found in the brain, ovary, liver, lung, thyroid gland and prostate and several subsets of leukocytes. ID2 expression is especially high in Natural Killer (NK-) cells, but is also found in CD4+ T cells, CD8+ T cells, monocytes and precursor B cells.

Nucleus.

Although it does not bind directly to DNA, by binding basic helix-loop-helix transcription factors through its HLH motif, ID2 may control tissue-specific genes related to cell growth, proliferation and differentiation (Hara et al., 1994; Iavarone et al., 1994). ID2 functions in cell fate decisions in early leukocyte development. Specifically, ID2 is required for NK-cell, innate lymphoid and lymphoid tissue inducer cells (Boos et al., 2007; Moro et al., 2010; Yokota et al., 1999). Furthermore, ID2 functions in the development of several dendritic cell subsets: Langerhans cells, cutaneous dendritic cells and splenic CD8a+ dendritic cells (Hacker et al., 2003). Although ID2 seems redundant for T-cell development in thymus, ID2 promotes NKT-cell development (Verykokakis et al., 2013), and it is involved in effector differentiation (Masson et al., 2013), as well as γδT cell homeostasis (Zhang et al., 2014). Finally, ID2 inhibits progression of precursor-B-cell development (Hara et al., 1997; Jensen et al., 2013), as well as activation-induced deaminase expression during B-cell responses (Gonda et al., 2003), likely through inhibition of E47 (Sayegh et al., 2003).
Besides leukocytes, ID2 has been found to function in erythrocyte development (Ji et al., 2008), enterocyte precursor and lung epithelial cell differentiation in mice (Rawlins et al., 2009). Furthermore, female mice lacking ID2 show lactation defects (Mori et al., 2000), and male mice have impaired spermatogenesis (Sablitzky et al., 1998).

ID2 is highly conserved in vertebrates, including mammals, reptiles, and fish.

No germinal mutations have been reported.

No somatic mutations have been reported.