Alternative titles; symbols
HGNC Approved Gene Symbol: CD164
Cytogenetic location: 6q21 Genomic coordinates (GRCh38) : 6:109,366,514-109,382,467 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 6q21 | ?Deafness, autosomal dominant 66 | 616969 | Autosomal dominant | 3 |
Sialomucins are a heterogeneous group of secreted or membrane-associated mucins that appear to play 2 key but opposing roles in vivo: first as cytoprotective or antiadhesive agents, and second as adhesion receptors. CD164 is a type I integral transmembrane sialomucin that functions as an adhesion receptor (Watt et al., 1998; Forde et al., 2007).
Using 2 monoclonal antibodies and a retroviral expression cloning strategy, Zannettino et al. (1998) isolated a cDNA encoding a novel transmembrane isoform of the mucin-like glycoprotein MGC24, which they designated CD164. The mature CD164 protein contains 178 amino acids, has a molecular mass of 80 to 90 kD, and is extremely rich in serine and threonine. CD164 was expressed by human CD34 (142230)-positive hematopoietic progenitor cells (HPCs).
Nyegaard et al. (2015) found expression of the Cd164 gene in sections of mouse cochlea at postnatal day 5. Expression was found in cochlear neurons and inner and outer hair cells of the organ of Corti, as well as in several other regions.
Zannettino et al. (1998) found that the CD164 receptor appeared to play a role in hematopoiesis by facilitating adhesion of CD34-positive cells to bone marrow stroma and by negatively regulating CD34-positive HPC growth. These functional effects were mediated by at least 2 spatially distinct epitopes, defined by specific monoclonal antibodies. Watt et al. (1998) found that these and other CD164 monoclonal antibodies showed distinct patterns of reactivity when analyzed on hematopoietic cells from normal human bone marrow, umbilical cord blood, and peripheral blood. Expression of the CD164 epitope was found on developing myelomonocytic cells in bone marrow, being downregulated on mature neutrophils but maintained on monocytes in the peripheral blood.
Using CD133 (PROM1; 604365)-positive HPCs and a T-cell line, Forde et al. (2007) demonstrated that CD164 associated with CXCR4 (162643). Antibody to the CD164 N-linked glycan-dependent epitope or CD164 knockdown via small interfering RNA inhibited migration of CD133-positive HPCs toward CXCL12 (600835), the CXCR4 ligand. CXCL12, in association with fibronectin (FN1; 135600), induced association of CD164 with CXCR4 following association of CXCR4 with the fibronectin receptors VLA4 (see ITGA4; 192975) and VLA5 (see ITGA5; 135620). CD164-CXCR4 association coincided with PKC-zeta (PRKCZ; 176982) and AKT (164730) signaling through CXCR4. Forde et al. (2007) concluded that an association among 3 distinct families of cell surface receptors, including CD164, regulates cell migratory responses and probably lends specificity to the homing and lodging of these cells within bone marrow.
Watt et al. (1998) identified PAC clones containing the CD164 gene and used these clones to localize the CD164 gene to chromosome 6q21 by FISH.
In affected members of a multigenerational Dutch family with autosomal dominant deafness-66 (DFNA66; 616969), Nyegaard et al. (2015) identified a heterozygous truncating mutation in the CD164 gene (R192X; 603356.0001). The mutation, which was found by a combination of linkage analysis and candidate gene sequencing, segregated with the disorder in the family. In vitro functional expression studies showed that the mutation resulted in abnormal intracellular trafficking of the mutant protein. Direct sequencing of the CD164 gene in 46 probands with deafness did not reveal any additional mutations.
In affected members of a multigenerational Dutch family with autosomal dominant deafness-66 (DFNA66; 616969), Nyegaard et al. (2015) identified a heterozygous c.574C-T transition (c.574C-T, NM_006016.4) at the end of exon 6 of the CD164 gene, resulting in an arg192-to-ter (R192X) substitution and the deletion of highly conserved residues in the C terminus that include the sorting motif. The mutation was predicted to affect only the membrane-bound isoforms (isoforms 1-3). The mutation, which was found by a combination of linkage analysis and candidate gene sequencing, segregated with the disorder in the family and was not found in any public database or in 1,200 unrelated Dutch control individuals. Transfection of the mutation into HEK293 cells showed that the mutant protein was located mostly at the plasma membrane, whereas the wildtype protein was predominantly located in intracellular vesicles, indicating abnormal intracellular trafficking of the mutant protein. Immunoprecipitation studies showed that the mutant protein was expressed and that it colocalized and formed heterodimers with wildtype CD164. However, there was no evidence of a dominant-negative effect on wildtype internalization.
Forde, S., Tye, B. J., Newey, S. E., Roubelakis, M., Smythe, J., McGuckin, C. P., Pettengell, R., Watt, S. M. Endolyn (CD164) modulates the CXCL12-mediated migration of umbilical cord blood CD133+ cells. Blood 109: 1825-1833, 2007. [PubMed: 17077324] [Full Text: https://doi.org/10.1182/blood-2006-05-023028]
Nyegaard, M., Rendtorff, N. D., Nielsen, M. S., Corydon, T. J., Demontis, D., Starnawska, A., Hedemand, A., Buniello, A., Niola, F., Overgaard, M. T., Leal, S. M., Ahmad, W., and 10 others. A novel locus harbouring a functional CD164 nonsense mutation identified in a large Danish family with nonsyndromic hearing impairment. PLoS Genet. 11: e1005386, 2015. Note: Electronic Article. [PubMed: 26197441] [Full Text: https://doi.org/10.1371/journal.pgen.1005386]
Watt, S. M., Buhring, H.-J., Rappold, I., Chan, J. Y.-H., Lee-Prudhoe, J., Jones, T., Zannettino, A. C. W., Simmons, P. J., Doyonnas, R., Sheer, D., Butler, L. H. CD164, a novel sialomucin on CD34+ and erythroid subsets, is located on human chromosome 6q21. Blood 92: 849-866, 1998. [PubMed: 9680353]
Zannettino, A. C. W., Buhring, H.-J., Niutta, S., Watt, S. M., Benton, M. A., Simmons, P. J. The sialomucin CD164 (MGC-24v) is an adhesive glycoprotein expressed by human hematopoietic progenitors and bone marrow stromal cells that serves as a potent negative regulator of hematopoiesis. Blood 92: 2613-2628, 1998. [PubMed: 9763543]