The gene is composed of 8 exons. The canonical transcript is 4619 bp long. Alternative splicing generates a soluble isoform lacking exon 6 and introducing a premature stop codon (Goodwin et al., 1990; Rose et al., 2009).

No pseudogene.

The precursor IL-7Rα protein includes a signal peptide (20 aminoacids) and has 459 aminoacids in total. The mature protein undergoes several post-translational modifications including glycosylation (6 potential N-glycosylation sites in the extracellular domain) and dissulfide bond formation. The extracellular domain has 219 aminoacids (spanning from aminoacids 21 to 239), the transmembrane domain has 25 aminoacids (spanning from aminoacids 240 to 264), and the cytoplasmic tail spans from aminoacids 265 - 459 (195 aminoacids). The soluble isoform of the receptor lacks the transmembrane domain (exon 6) and, due to an altered translation reading frame, it thereafter contains 27 unique aminoacids in the C-terminus (Goodwin et al., 1990; Rose et al., 2009).

IL-7Rα expression and signaling is required for normal T-cell development and homeostasis (Puel et al., 1998; Ribeiro et al., 2013). Although IL-7 signaling is not required for normal human B-cell development (in contrast to the mouse, where it is fundamental) IL-7Rα is also expressed in B-cell precursors (Mazzucchelli and Durum, 2007).

The functional protein is localized at the plasma membrane where it forms an heterodimeric complex with the common gamma chain (IL-2Rγ, CD132) to transduce IL-7 signaling or the cytokine receptor-like factor 2/ thymic stromal lymphopoietin receptor (CRLF2/TSLPR) to transduce TSLP signaling. IL-7Rα endocytosis via clathrin-coated pits appears to be required for maximal IL-7-mediated signaling (Henriques et al., 2010).

IL-7Rα mediates the signaling of IL-7 and TSLP cytokines. The cytoplasmic tail of IL-7R associates directly with JAK1 to transduce intracellular signaling together with JAK3 or JAK2 that are associated with the IL-2Rγ or TSLPR, respectively. The intracellular signaling pathways activated upon IL-7/IL-7R engagement in T-cells are the JAK/STAT (Lin et al., 1995; Rosenthal et al., 1997), PI3K/Akt/mTOR (Dadi and Roifman, 1993; Venkitaraman and Cowling, 1994; Rathmell et al., 2001) and, in some instances, MEK/Erk (Fleming and Paige, 2001; Maki and Ikuta, 2008; Patel and Chang, 2012).
IL-7/IL-7R signaling is required for T-cell development at different stages. At the double-negative stage (DN; CD4- CD8-), it is required for survival and proliferation of T-cells. It is also required to initiate the recombination of the TCRγ locus (Ye et al., 2001), the reason why it is absolutely required for γδ T-cell development. The receptor is down-regulated at the double-positive stage (DP; CD4+ CD8+) and up-regulated again at the single-positive stage (SP; CD4+ or CD8+). At this stage, IL-7R appears to be involved in CD4 versus CD8 lineage specification (at least in the mouse, possibly in humans) and overall cell survival (Park et al., 2010; Sinclair et al., 2011). Mature T-cells also benefit from IL-7R signaling for homeostatic maintenance and function (Soares et al., 1998).
The function of the TSLP/IL-7R signaling is much less known. Most studies, suggest an important role in the normal function of dendritic cells, immune tolerance and allergy (Watanabe et al., 2005; Lee et al., 2008; reviewed in Ziegler, 2012 and Hanabuchi et al., 2012).

IL-7R displays aminoacid sequence identity with other human cytokine receptors, such as IL-2R (14.6%), IL-6R (13.2%) GM-CSF receptor (16.0%) GH receptor (12.9%) (Goodwin et al., 1990).
Orthologs of the human IL-7R are found in other species. The murine Il7r has 64%/67.2% DNA/protein identity (Goodwin et al., 1990) and the zebrafish il7r has 20.5% protein identity (Liongue and Ward, 2007) compared with the human receptor.

Hereditary recessive inactivating mutations in the IL7R gene have been found to cause severe combined immunodeficiency (SCID)(Puel et al., 1998; Roifman et al., 2000; Jo et al., 2004; Giliani et al., 2005). The mutations occur in the extracellular domain coding region and comprise missense, nonsense mutations and splicing affecting mutations. The IL-7R SCID is characterized as T-B+NK+. The treatment is hematopoietic stem cell transplantation.

Somatic and heterozygous IL7R gain-of-funtion gene mutations have been found in around 9-10% of childhood T-cell acute lymphoblastic leukemia (T-ALL) cases (Zenatti et al., 2011; Shochat et al., 2011; Zhang et al., 2012). Later, mutations in the IL7R in adult T-ALL (1.7%) were also found (Kim et al., 2013). So far, all T-ALL mutations described are restricted to exon 6, affecting the extracellular juxtamembrane-transmembrane domain of the protein. The mutations are in-frame insertions or deletions-insertions. The majority include an unpaired cysteine addition responsible for the homodimerization of two IL7-Rα chains via disulphide bond formation. The dimerization of the receptor leads to ligand-independent constitutive signaling via JAK1 (Zenatti et al., 2011), contrasting with the physiological heterodimeric IL-7-dependent activation of the receptor that additionally requires IL-2Rγ and JAK3.
IL7R somatic, heterozygous mutations have also been described in a small fraction of B-cell ALL (B-ALL) cases (less than 1%), significantly associated with aberrant TSLPR expression (Shochat et al., 2011). These included similar mutations to those found in T-ALL, as well as, in half of the cases, mutations in exon 5 leading to an S185C aminoacid substitution (Shochat et al., 2011).