Alternative titles; symbols
HGNC Approved Gene Symbol: ICA1
Cytogenetic location: 7p21.3 Genomic coordinates (GRCh38): 7:8,113,184-8,262,555 (from NCBI)
Pietropaolo et al. (1993) identified a novel 69-kD peptide autoantigen (ICA69) associated with insulin-dependent diabetes mellitus (IDDM; see 222100) by screening a human islet lambda-gt11 cDNA expression library with cytoplasmic islet cell antibody positive sera from relatives of IDDM patients who progressed to the overt disease. The deduced open reading frame of the ICA69 cDNA predicted a 483-amino acid protein. ICA69 showed no nucleotide or amino acid sequence relation to any known sequence in GenBank except for 2 short regions of similarity with bovine serum albumin (BSA). The ICA69 cDNA probe hybridized with a 2-kb mRNA in polyadenylated RNA from human pancreas, brain, heart, thyroid, and kidney. The structural gene for ICA69 was designated ICA1.
Gaedigk et al. (1996) cloned human and mouse ICA1 cDNAs and identified alternatively spliced mRNA transcripts. All splice variants encoded the conserved T-cell epitope (in exon 2) recognized by autoreactive T cells in diabetic children and diabetes-prone nonobese diabetic (NOD) mice.
Pietropaolo et al. (1993) mapped the mouse homolog of ICA1 to the proximal end of chromosome 6, within 6 cM of the MET protooncogene (164860). By isotopic in situ hybridization, Gaedigk et al. (1994) mapped the ICA1 gene to human 7p22.
Gaedigk et al. (1996) reported that the mouse Ica1 gene is distributed over more than 100 kb on chromosome 6. The single murine genomic locus contains 14 coding exons, ranging from 39 to 271 bp in length. They found that the human and mouse intron/exon junctions are identical.
ICA69 is expressed in salivary and lacrimal glands. In NOD mice, in which loss of salivary secretory function develops spontaneously (as in human Sjogren syndrome; 270150), Winer et al. (2002) found that disruption of the Ica69 gene prevented lacrimal gland disease and greatly reduced salivary gland disease. These animals developed type 1 diabetes (222100) with slight delay but at much the same incidence as wildtype animals, assigning a facultative rather than obligate role to ICA69 in the development of diabetes.
Gaedigk, R., Duncan, A. M. V., Miyazaki, I., Robinson, B. H., Dosch, H.-M. ICA1 encoding p69, a protein linked to the development of type 1 diabetes, maps to human chromosome 7p22. Cytogenet. Cell Genet. 66: 274-276, 1994. [PubMed: 8162706] [Full Text: https://doi.org/10.1159/000133711]
Gaedigk, R., Karges, W., Hui, M. F., Scherer, S. W., Dosch, H.-M. Genomic organization and transcript analysis of ICAp69, a target antigen in diabetic autoimmunity. Genomics 38: 382-391, 1996. [PubMed: 8975715] [Full Text: https://doi.org/10.1006/geno.1996.0641]
Pietropaolo, M., Castano, L., Babu, S., Buelow, R., Kuo, Y.-L. S., Martin, S., Martin, A., Powers, A. C., Prochazka, M., Naggert, J., Leiter, E. H., Eisenbarth, G. S. Islet cell autoantigen 69 kD (ICA69): molecular cloning and characterization of a novel diabetes-associated autoantigen. J. Clin. Invest. 92: 359-371, 1993. [PubMed: 8326004] [Full Text: https://doi.org/10.1172/JCI116574]
Winer, S., Astsaturov, I., Cheung, R., Tsui, H., Song, A., Gaedigk, R., Winer, D., Sampson, A., McKerlie, C., Bookman, A., Dosch, H.-M. Primary Sjogren's syndrome and deficiency of ICA69. Lancet 360: 1063-1069, 2002. [PubMed: 12383988] [Full Text: https://doi.org/10.1016/S0140-6736(02)11144-5]