Alt. symbols: IL10R | HIL-10R | CDW210A | CD210a | CD210

Approved name: interleukin 10 receptor subunit alpha
Alt. names: interleukin 10 receptor, alpha

Location: 11q23.3: 117986370 - 118003037 (+)
Gene type: protein_coding, 12 transcripts.

Scores: LoFtool: 0.137000 | pLI: 0.96834586 | LOEUF: 0.685

HGNC: 5964

NCBI: 3587, RefSeq: NG_016275.1

Ensembl: ENSG00000110324.12

LRG_151 | Status: public

OMIM: 146933

Expression | ProteinAtlas

IL10RA encodes the alpha subunit of the receptor for IL-10. This receptor, which is structurally related to the interferon receptors, has been shown to mediate the immunosuppressive signaling of IL-10, as well as to promote myeloid progenitor cell survival through the insulin receptor substrate-2/PI 3-kinase/AKT pathway (PMID: 11591769). Upon alpha subunit engagement by IL-10, a conformational change occurs in the beta subunit of the receptor to allowing the latter to bind IL10 as well (PMID: 16982608). Then, this heterotetrameric complex, composed of two alpha and two beta subunits, activates the constitutively associated kinases JAK1 and TYK2 (PMID: 12133952), which then phosphorylate specific tyrosine residues in the intracellular domain of the alpha subunit, leading to STAT3 recruitment and phosphorylation. Phosphorylated STAT3 then homodimerizes, translocates to the nucleus, and activates the expression of anti-inflammatory genes. This pathway may also prevent starvation-induced autophagy in fibroblasts via crosstalk with mTOR-AKT signaling (PMID: 26962683).

Biallelic LOF mutations in genes encoding either IL-10 (IL10) or its receptors (IL10RA for IL-10R1 and IL10RB for IL-10R2) have been associated with autosomal recessive forms of early or very early onset inflammatory bowel disease (V/EO-IBD) [OMIM: 612567, 613148]. In addition to severe and progressive colitis presenting as bloody diarrhea often within the first 3 months of life, patients also have failure to thrive, recurrent fevers and infections, abscesses and perianal fistula formation, oral aphthous lesions, folliculitis, and arthritis (PMID: 20934598, 22549091). Immunophenotyping shows grossly normal lymphocyte numbers and T cell proliferative responses, along with normal specific antibody responses to vaccinations but elevated IgG, IgA, and IgM levels in some patients. In patients with IL10 deficiency, circulating IL-10 levels are expectedly low to absent, but in patients with deficiencies in the receptor subunits, serum IL-10 levels may be normal or elevated (PMID: 19890111, 21519361, 22476154). Because patients with these conditions often have severe, treatment-refractory IBD, early consideration should be given to HSCT (PMID: 23158016). Moreover, patients appear to also have predisposition towards the development of B-cell lymphomas (PMID: 24089328). Most IL10RA mutations are missense, including homozygosity for Gly141Arg, Thr84Ile (PMID: 19890111) and Arg262Cys (PMID: 21519361), in addition to compound heterozygosity for Arg101Trp with Thr84Ile (PMID: 22476154), and Ser195Pro with Lys456Asn (PMID: 24813381). [Load More]