Alternative titles; symbols
HGNC Approved Gene Symbol: HMMR
Cytogenetic location: 5q34 Genomic coordinates (GRCh38) : 5:163,460,632-163,491,941 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 5q34 | {Breast cancer, susceptibility to} | 114480 | Autosomal dominant; Somatic mutation | 3 |
Hardwick et al. (1992) cloned a hyaluronan receptor cDNA from mouse 3T3 cells. The 2.9-kb cDNA codes for a predicted 477-amino acid protein, which they designated RHAMM. Antibodies directed against the protein blocked locomotion of cells induced by expression of a mutant H-ras (190020). Savani et al. (1995) showed that RHAMM is upregulated in response to wound healing. When hyaluronan binds to RHAMM the phosphorylation of a number of proteins, including the focal adhesion kinase pp125-FAK (600758), occurs (Hall et al., 1994). The latter is a necessary step for disassembly of focal contacts and subsequent motility.
Entwistle et al. (1995) showed that the mouse Rhamm gene contains at least 14 exons spanning greater than 15 kb and can produce alternatively spliced mRNAs, one of which is transforming (Hall et al., 1995), similar to the hyaluronan receptor CD44 (107269).
Pujana et al. (2007) used a network modeling strategy to identify genes potentially associated with higher risk of breast cancer. Starting with 4 genes encoding known tumor suppressors of breast cancer, they combined gene expression profiling with functional genomic and proteomic data from various species to generate a network containing 118 genes linked by 866 potentially functional associations. This network showed higher connectivity than expected by chance, suggesting that its components function in biologically related pathways. Pujana et al. (2007) showed that HMMR, encoding a centrosome subunit, and 2 of its interactors, SMC3 (606062) and MAD1L1 (602686), associate in protein complexes with BRCA1 (113705) and BRCA2 (600185). Pujana et al. (2007) established that HMMR is an in vitro substrate for BRCA1-BARD1 (601593)-mediated polyubiquitination and that BRCA1 and HMMR genetically interact to control centrosome number in breast tumor- and mammary epithelium-derived cell lines. In addition, they identified an association in breast tumorigenesis between BRCA1 and HMMR with AURKA (603072), which is also in the BRCA-centered network (BCN).
Spicer et al. (1995) used interspecific backcross analysis to map the mouse gene to chromosome 11 within a region of synteny to human chromosome 5q23-q35. They used somatic cell hybrid DNAs and a radiation hybrid panel to confirm the distal 5q map location (5q33.2-qter) of the HMMR gene in human.
Pujana et al. (2007) genotyped 3 HMMR haplotype-tagging single-nucleotide polymorphisms (htSNPs) in 923 individually matched case-control pairs from a population-based study of incident breast cancer in northern Israel and identified statistically significant associations for each htSNP. They confirmed this association in an independent Ashkenazi Jewish cohort. A significant association of a 12-month-earlier age of onset in homozygous cases as compared with controls was found in a third cohort.
Entwistle, J., Zhang, S., Yang, B., Wong, C., Li, Q., Hall, C. L., Jingbo, A., Mowat, M., Greenberg, A. H., Turley, E. A. Characterization of the murine gene encoding the hyaluronan receptor RHAMM. Gene 163: 233-238, 1995. [PubMed: 7590272] [Full Text: https://doi.org/10.1016/0378-1119(95)00398-p]
Hall, C., Yang, B., Yang, X., Zhang, S., Turley, M., Samuel, S., Lange, L. A., Wang, C., Curpen, G. D., Savani, R. C., Greenberg, A. H., Turley, E. A. Overexpression of the hyaluronan receptor RHAMM is transforming and is also required for H-ras transformation. Cell 82: 19-28, 1995. [PubMed: 7541721] [Full Text: https://doi.org/10.1016/0092-8674(95)90048-9]
Hall, C. L., Wang, C., Lange, L. A., Turley, E. A. Hyaluronan and the hyaluronan receptor RHAMM promote focal adhesion turnover and transient tyrosine kinase activity. J. Cell Biol. 126: 575-588, 1994. [PubMed: 7518470] [Full Text: https://doi.org/10.1083/jcb.126.2.575]
Hardwick, C., Hoare, K., Owens, R., Hohn, H. P., Moore, D., Cripps, V., Austen, L., Nance, D. M., Turley, E. A. Molecular cloning of a novel hyaluronan receptor that mediates tumor cell motility. J. Cell Biol. 117: 1343-1350, 1992. Note: Erratum: J. Cell Biol. 118: 753 only, 1992. [PubMed: 1376732] [Full Text: https://doi.org/10.1083/jcb.117.6.1343]
Pujana, M. A., Han, J.-D. J., Starita, L. M., Stevens, K. N., Tewari, M., Ahn, J. S., Rennert, G., Moreno, V., Kirchhoff, T., Gold, B., Assmann, V., ElShamy, W. M., and 22 others. Network modeling links breast cancer susceptibility and centrosome dysfunction. Nature Genet. 39: 1338-1349, 2007. [PubMed: 17922014] [Full Text: https://doi.org/10.1038/ng.2007.2]
Savani, R. C., Wang, C., Yang, B. H., Zhang, S. W., Kinsella, M. G., Wight, T. N., Stern, R., Nance, D. M., Turley, E. A. Migration of bovine aortic smooth muscle cells after wounding injury: the role of hyaluronan and RHAMM. J. Clin. Invest. 95: 1158-1168, 1995. [PubMed: 7533785] [Full Text: https://doi.org/10.1172/jci117764]
Spicer, A. P., Roller, M. L., Camper, S. A., McPherson, J. D., Wasmuth, J. J., Hakim, S., Wang, C., Turley, E. A., McDonald, J. A. The human and mouse receptors for hyaluronan-mediated motility, RHAMM, genes (HMMR) map to human chromosome 5q33.2-qter and mouse chromosome 11. Genomics 30: 115-117, 1995. [PubMed: 8595891] [Full Text: https://doi.org/10.1006/geno.1995.0022]