Alternative titles; symbols
HGNC Approved Gene Symbol: CHML
Cytogenetic location: 1q43 Genomic coordinates (GRCh38): 1:241,628,851-241,640,369 (from NCBI)
Using the mouse homolog of the human choroideremia cDNA as a probe, Cremers et al. (1992) identified a homologous human gene, which they designated CHML for choroideremia-like. The cDNA encompassed an open reading frame of 1,968 bp.
The product of the CHML gene, REP2, supports geranylgeranylation of most Rab proteins and may substitute for REP1 (300390) in tissues other than retina (Cremers et al., 1992).
Using semisynthetic fluorescent RAB27A (603868), Rak et al. (2004) demonstrated that although RAB27A can be prenylated by REP2, this reaction can be effectively inhibited by other RAB proteins, providing a possible explanation for the accumulation of unprenylated RAB27A in choroideremia (303100) resulting from REP1 deficiency.
By hybridization to a panel of human-rodent somatic cell hybrids, Cremers et al. (1992) localized the CHML gene to 1q31-qter. Since by linkage analysis the gene for Usher syndrome type II (USH2; 276901) is located in the same region and because of the clinical similarities between choroideremia and Usher syndrome type II, they suggested that CHML is a candidate gene for that disorder. The existence of the CHML gene may explain why deletion of the X-linked gene for RAB geranylgeranyltransferase component A results only in retinal degeneration. One would expect that this molecule would be crucial for secretion and exocytosis in all cells.
Van Bokhoven et al. (1994) mapped the CHML gene to 1q42-qter by study of a human/rodent hybrid cell line. USH2 mapped to the same chromosomal segment as evidenced by the fact that the D1S58, a polymorphic marker previously shown to be located proximal to the USH2 locus, was also assigned to the 1q42-qter segment.
By genomic sequence analysis, Halford et al. (2001) determined that the CHML gene lies within intron 1 of the OPN3 gene (606695) on chromosome 1q43.
To investigate a possible role of the CHML gene in the pathogenesis of USH2, van Bokhoven et al. (1994) investigated 10 Dutch and 9 Danish USH2 patients for point mutations in the open reading frame of the CHML gene. Using PCR/single-strand conformation polymorphism analysis and direct sequencing, they found no disease-specific mutations and concluded that the CHML is not involved in the pathogenesis of USH2.
Cremers, F. P. M., Molloy, C. M., van de Pol, D. J. R., van den Hurk, J. A. J. M., Bach, I., Geurts van Kessel, A. H. M., Ropers, H.-H. An autosomal homologue of the choroideremia gene colocalizes with the Usher syndrome type II locus on the distal part of chromosome 1q. Hum. Molec. Genet. 1: 71-75, 1992. [PubMed: 1301160] [Full Text: https://doi.org/10.1093/hmg/1.2.71]
Halford, S., Freedman, M. S., Bellingham, J., Inglis, S. L., Poopalasundaram, S., Soni, B. G., Foster, R. G., Hunt, D. M. Characterization of a novel human opsin gene with wide tissue expression and identification of embedded and flanking genes on chromosome 1q43. Genomics 72: 203-208, 2001. [PubMed: 11401433] [Full Text: https://doi.org/10.1006/geno.2001.6469]
Rak, A., Pylypenko, O., Niculae, A., Pyatkov, K., Goody, R. S., Alexandrov, K. Structure of the Rab7:REP-1 complex: insights into the mechanism of Rab prenylation and choroideremia disease. Cell 117: 749-760, 2004. [PubMed: 15186776] [Full Text: https://doi.org/10.1016/j.cell.2004.05.017]
van Bokhoven, H., van Genderen, C., Molloy, C. M., van de Pol, D. J. R., Cremers, C. W. R. J., van Aarem, A., Schwartz, M., Rosenberg, T., Geurts van Kessel, A. H. M., Ropers, H.-H., Cremers, F. P. M. Mapping of the choroideremia-like (CHML) gene at 1q42-qter and mutation analysis in patients with Usher syndrome type II. Genomics 19: 385-387, 1994. [PubMed: 8188272] [Full Text: https://doi.org/10.1006/geno.1994.1077]