Alternative titles; symbols
HGNC Approved Gene Symbol: ICAM4
Cytogenetic location: 19p13.2 Genomic coordinates (GRCh38): 19:10,286,955-10,288,520 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 19p13.2 | [Blood group, Landsteiner-Wiener] | 111250 | 3 |
Intracellular adhesion molecule-4 (ICAM4) is a member of the immunoglobulin (Ig) gene superfamily and encodes the Landsteiner-Wiener (LW) blood group antigens (111250) (Bailly et al., 1994; Bailly et al., 1995).
Bailly et al. (1994) cloned ICAM4 cDNAs from a human bone marrow cDNA library. One form encodes a single-spanning transmembrane protein of 270 amino acids, including a 29-amino acid signal peptide. A second form encodes a shortened protein of 236 residues without transmembrane and cytoplasm domains. The predicted protein shares approximately 30% identity with intercellular adhesion molecules ICAM1 (147840), ICAM2 (146630), and ICAM3 (146631), which are the counterreceptors for the lymphocyte function-associated antigen LFA1 (see 153370 and 600065). The extracellular domain of ICAM4 consists, like that of ICAM2, of 2 Ig-like domains, and the critical residues involved in binding of LFA1 to ICAMs are partially conserved in ICAM4.
Using RT-PCR, Hermand et al. (1995) cloned ICAM4 from whole blood RNA. The sequence was identical to that of the full-length cDNA reported by Bailly et al. (1994) except for differences in the region encoding the signal sequence. The corrected ICAM4 sequence reported by Hermand et al. (1995) encodes a 271-amino acid protein with a 30-amino acid signal peptide.
Hermand et al. (1996) characterized the ICAM4 gene, which contains 3 exons spanning approximately 2.65 kb.
ICAM4 maps to chromosome 19p13.2, based on the previous mapping of the LW locus to this location (Hermand et al., 1995).
Bailly et al. (1995) purified the ICAM4 (LW) protein from red cells and found that the protein bound to the leukocyte CD11a/CD18 and CD11b/CD18 integrins (see 600065). They speculated that ICAM4 may be involved in regulation of red cell turnover.
LW Blood Group System: LW(a)/LW(b) Polymorphism
Hermand et al. (1995) determined that the LW(a)/LW(b) polymorphism of the LW blood group system (111250) is determined by a single-basepair substitution in the ICAM4 gene (614088.0001).
LW Blood Group System: LW(a-b-) Phenotype
Using Southern blot analysis, Hermand et al. (1995) showed that the ICAM4 gene was not grossly rearranged in an individual with the LW(a-b-) phenotype of the LW blood group system (111250) or in individuals with the Rh-null phenotype, who also lack LW antigens. RFLP analysis using PvuII indicated that the LW(a-b-) individual and 3 Rh-null individuals were homozygous for a phenotypically silent LW(a) allele.
In an individual with the LW(a-b-) phenotype who carried a normal Rh phenotype, Hermand et al. (1996) found a 10-bp deletion in the ICAM4 gene (614088.0002) that generated a premature stop codon and encoded a truncated protein without the transmembrane and cytoplasmic domains. Heterogeneity was indicated by the fact that no detectable abnormality of the LW gene or transcript could be detected in another LW(a-b-) individual.
Hermand et al. (1995) demonstrated that the molecular basis for the LW(a)/LW(b) polymorphism of the LW blood group system (111250) is an A-to-G change at nucleotide 299 (relative to the translation initiation site) of the ICAM4 gene that correlates with a PvuII restriction site and results in a gln100-to-arg (Q100R) amino acid substitution. COS-7 cells transfected with LW(a) or LW(b) cDNAs reacted with human anti-LW(a) and anti-LW(b) sera, respectively, as well as with a murine monoclonal anti-LW(ab) antibody, as shown by flow cytometry analysis. Hermand et al. (1995) referred to this polymorphism as an A-to-G change at nucleotide 308 (relative to the transcription initiation site), resulting in a GLN70ARG (Q70R) substitution (numbering using the mature ICAM4 protein sequence, after removal of the signal peptide).
In an individual with the rare LW(a-b-) phenotype of the LW blood group system (111250) who carried a normal Rh phenotype, Hermand et al. (1996) identified a 10-bp deletion (ACCTGCGCAG) at nucleotide 346 (relative to the translation initiation site) in exon 1 of the ICAM4 gene. The deletion generated a premature stop codon, resulting in a truncated protein without the transmembrane and cytoplasmic domains. Heterogeneity was indicated by the fact that no detectable abnormality of the ICAM4 gene or transcript could be detected in another LW(a-b-) individual. Hermand et al. (1996) referred to this mutation as a 10-bp deletion at nucleotide 355 (relative to the transcription initiation site).
Bailly, P., Hermand, P., Callebaut, I., Sonneborn, H. H., Khamlichi, S., Mornon, J.-P., Cartron, J.-P. The LW blood group glycoprotein in homologous to intercellular adhesion molecules. Proc. Nat. Acad. Sci. 91: 5306-5310, 1994. [PubMed: 8202485] [Full Text: https://doi.org/10.1073/pnas.91.12.5306]
Bailly, P., Tontti, E., Hermand, P., Cartron, J.-P., Gahmberg, C. G. The red cell LW blood group protein is an intercellular adhesion molecule which binds to CD11/CD18 leukocyte integrins. Europ. J. Immun. 25: 3316-3320, 1995. [PubMed: 8566017] [Full Text: https://doi.org/10.1002/eji.1830251217]
Hermand, P., Gane, P., Mattei, M. G., Sistonen, P., Cartron, J.-P., Bailly, P. Molecular basis and expression of the LW(a)/LW(b) blood group polymorphism. Blood 86: 1590-1594, 1995. [PubMed: 7632968]
Hermand, P., Le Pennec, P. Y., Rouger, P., Cartron, J.-P., Bailly, P. Characterization of the gene encoding the human LW blood group protein in LW(+) and LW(-) phenotypes. Blood 87: 2962-2967, 1996. [PubMed: 8639917]