Entry - *604509 - INTERLEUKIN 18 RECEPTOR ACCESSORY PROTEIN; IL18RAP - OMIM - (OMIM.ORG)

 
 
* 604509

INTERLEUKIN 18 RECEPTOR ACCESSORY PROTEIN; IL18RAP


Alternative titles; symbols

INTERLEUKIN 18 RECEPTOR, BETA CHAIN; IL18RB
ACCESSORY PROTEIN-LIKE; ACPL


HGNC Approved Gene Symbol: IL18RAP

Cytogenetic location: 2q12.1   Genomic coordinates (GRCh38) : 2:102,418,621-102,452,565 (from NCBI)


TEXT

▼ Cloning and Expression

Interleukin-18 (IL18; 600953) binds to IL18R1 (604494), a receptor with sequence homology to IL1 receptors. Signaling by IL1 (147760, 147720) through IL1R1 (147810) also requires the presence of the IL1 receptor accessory protein (IL1RACP; 602626) to increase the affinity of IL1R for IL1. By searching the EST database for a molecule homologous to IL1RACP, Born et al. (1998) identified the interleukin-18 receptor accessory protein (IL18RAP), which they called ACPL (accessory protein-like). IL18RAP was unable to mediate signaling by IL1 but did play a role in signaling by IL18. By screening an EL46.1 cDNA library with an IMAGE clone, Born et al. (1998) obtained the full-length open reading frame for the 600-amino acid protein. IL18RAP shares 65% amino acid identity with the homologous mouse protein and 25 to 27% identity with members of the IL1R family. IL18RAP is predicted to contain a 14-amino acid signal peptide, a 342-amino acid extracellular (Ig superfamily-like) segment, a single transmembrane region, and a 222-amino acid cytoplasmic domain that is 32% identical to IL1R1. Northern blot analysis revealed that IL18RAP mRNA, present predominantly as a 3.8-kb product, was expressed strongly in peripheral blood leukocytes, spleen, lung, and, to a lesser extent, in colon, but not in any other tissue tested.

By Western blot analysis of peripheral blood mononuclear cells, Koskinen et al. (2009) detected full-length IL18RAP as a band at 70 kD and a second band at 37 kD, suggesting a putative alternative isoform of IL18RAP.


▼ Mapping

By radiation hybrid analysis, Born et al. (1998) mapped the IL18RAP gene to chromosome 2, near the IL18R1 and IL1R1 loci.


▼ Gene Function

Born et al. (1998) found that although IL18RAP did not bind IL18 in vitro, coexpression of IL18R1 and IL18RAP was required for IL18 responsiveness in terms of NF-kappa-B (see 164011) and JNK (see 601158) activation. Furthermore, a mutant version of IL18RAP lacking the cytoplasmic domain inhibited IL18 signaling.


▼ Molecular Genetics

For discussion of a possible association between variation in the IL18RAP gene and susceptibility to celiac disease, see CELIAC8 (612006).

For discussion of a possible association between variation in the IL18RAP gene and susceptibility to Crohn disease and ulcerative colitis, see IBD1 (266600).

For discussion of a possible association between variation in the IL18RAP gene and susceptibility to leprosy, see 609888.

▼ REFERENCES

  1. Born, T. L., Thomassen, E., Bird, T. A., Sims, J. E. Cloning of a novel receptor subunit, AcPL, required for interleukin-18 signaling. J. Biol. Chem. 273: 29445-29450, 1998. [PubMed: 9792649, related citations] [Full Text]

  2. Koskinen, L. L. E., Einarsdottir, E., Dukes, E., Heap, G. A. R., Dubois, P., Korponay-Szabo, I. R., Kaukinen, K., Kurppa, K., Ziberna, F., Vatta, S., Not, T., Ventura, A., and 9 others. Association study of the IL18RAP locus in three European populations with coeliac disease. Hum. Molec. Genet. 18: 1148-1155, 2009. [PubMed: 19103669, related citations] [Full Text]


Contributors:
Paul J. Converse - updated : 11/14/2012
George E. Tiller - updated : 11/10/2009
Marla J. F. O'Neill - updated : 6/12/2008
Creation Date:
Paul J. Converse : 2/4/2000
Edit History:
carol : 05/03/2019
mgross : 11/14/2012
mgross : 11/14/2012
wwang : 11/10/2009
carol : 10/22/2009
carol : 6/12/2008
mgross : 5/2/2005
carol : 2/4/2000
carol : 2/4/2000

* 604509

INTERLEUKIN 18 RECEPTOR ACCESSORY PROTEIN; IL18RAP


Alternative titles; symbols

INTERLEUKIN 18 RECEPTOR, BETA CHAIN; IL18RB
ACCESSORY PROTEIN-LIKE; ACPL


HGNC Approved Gene Symbol: IL18RAP

Cytogenetic location: 2q12.1   Genomic coordinates (GRCh38) : 2:102,418,621-102,452,565 (from NCBI)


TEXT

Cloning and Expression

Interleukin-18 (IL18; 600953) binds to IL18R1 (604494), a receptor with sequence homology to IL1 receptors. Signaling by IL1 (147760, 147720) through IL1R1 (147810) also requires the presence of the IL1 receptor accessory protein (IL1RACP; 602626) to increase the affinity of IL1R for IL1. By searching the EST database for a molecule homologous to IL1RACP, Born et al. (1998) identified the interleukin-18 receptor accessory protein (IL18RAP), which they called ACPL (accessory protein-like). IL18RAP was unable to mediate signaling by IL1 but did play a role in signaling by IL18. By screening an EL46.1 cDNA library with an IMAGE clone, Born et al. (1998) obtained the full-length open reading frame for the 600-amino acid protein. IL18RAP shares 65% amino acid identity with the homologous mouse protein and 25 to 27% identity with members of the IL1R family. IL18RAP is predicted to contain a 14-amino acid signal peptide, a 342-amino acid extracellular (Ig superfamily-like) segment, a single transmembrane region, and a 222-amino acid cytoplasmic domain that is 32% identical to IL1R1. Northern blot analysis revealed that IL18RAP mRNA, present predominantly as a 3.8-kb product, was expressed strongly in peripheral blood leukocytes, spleen, lung, and, to a lesser extent, in colon, but not in any other tissue tested.

By Western blot analysis of peripheral blood mononuclear cells, Koskinen et al. (2009) detected full-length IL18RAP as a band at 70 kD and a second band at 37 kD, suggesting a putative alternative isoform of IL18RAP.


Mapping

By radiation hybrid analysis, Born et al. (1998) mapped the IL18RAP gene to chromosome 2, near the IL18R1 and IL1R1 loci.


Gene Function

Born et al. (1998) found that although IL18RAP did not bind IL18 in vitro, coexpression of IL18R1 and IL18RAP was required for IL18 responsiveness in terms of NF-kappa-B (see 164011) and JNK (see 601158) activation. Furthermore, a mutant version of IL18RAP lacking the cytoplasmic domain inhibited IL18 signaling.


Molecular Genetics

For discussion of a possible association between variation in the IL18RAP gene and susceptibility to celiac disease, see CELIAC8 (612006).

For discussion of a possible association between variation in the IL18RAP gene and susceptibility to Crohn disease and ulcerative colitis, see IBD1 (266600).

For discussion of a possible association between variation in the IL18RAP gene and susceptibility to leprosy, see 609888.

REFERENCES

  1. Born, T. L., Thomassen, E., Bird, T. A., Sims, J. E. Cloning of a novel receptor subunit, AcPL, required for interleukin-18 signaling. J. Biol. Chem. 273: 29445-29450, 1998. [PubMed: 9792649] [Full Text: https://doi.org/10.1074/jbc.273.45.29445]

  2. Koskinen, L. L. E., Einarsdottir, E., Dukes, E., Heap, G. A. R., Dubois, P., Korponay-Szabo, I. R., Kaukinen, K., Kurppa, K., Ziberna, F., Vatta, S., Not, T., Ventura, A., and 9 others. Association study of the IL18RAP locus in three European populations with coeliac disease. Hum. Molec. Genet. 18: 1148-1155, 2009. [PubMed: 19103669] [Full Text: https://doi.org/10.1093/hmg/ddn438]


Contributors:
Paul J. Converse - updated : 11/14/2012
George E. Tiller - updated : 11/10/2009
Marla J. F. O'Neill - updated : 6/12/2008

Creation Date:
Paul J. Converse : 2/4/2000

Edit History:
carol : 05/03/2019
mgross : 11/14/2012
mgross : 11/14/2012
wwang : 11/10/2009
carol : 10/22/2009
carol : 6/12/2008
mgross : 5/2/2005
carol : 2/4/2000
carol : 2/4/2000



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OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University.
Copyright® 1966-2025 Johns Hopkins University.

NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University.
Copyright® 1966-2025 Johns Hopkins University.
Printed: June 19, 2025