Alternative titles; symbols
HGNC Approved Gene Symbol: COLEC10
Cytogenetic location: 8q24.12 Genomic coordinates (GRCh38) : 8:118,952,263-119,108,455 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 8q24.12 | 3MC syndrome 3 | 248340 | Autosomal recessive | 3 |
COLEC10 is a member of the collectin subfamily of C-type lectins. Collectins contain collagen-like sequences and carbohydrate recognition domains.
By searching an EST database and screening a liver cDNA library, Ohtani et al. (1999) isolated a cDNA encoding COLEC10, which they called CLL1. The deduced 277-amino acid COLEC10 protein contains an N-terminal domain, a collagen-like domain, a neck region predicted to mediate formation of a triple-helical structure, and a C-terminal conserved carbohydrate recognition domain. Unlike the cysteine-rich N-terminal domains of other collectins, the N-terminal domain of COLEC10 has only 1 cysteine. Northern blot analysis detected 1.2- and 3.8-kb transcripts expressed primarily in liver, with much lower levels in placenta. The 1.2-kb transcript was expressed at higher levels in both tissues. RT-PCR analysis showed expression in all tissues tested except skeletal muscle. Western blot analysis of fractionated human liver detected COLEC10 in the cytosolic fraction, and immunofluorescence analysis localized COLEC10 to the cytoplasm of cultured primary hepatocytes.
Munye et al. (2017) assessed intracellular localization of CLL1 in cells from the ATDC5 mouse chondrocyte cell line and observed expression in the Golgi apparatus consistent with a secreted peptide, colocalization with the trans-Golgi network marker 58K, and cytosolic expression. In addition, CLL1 colocalized with laminin in the basal lamina. Analysis of CLL1 during mouse craniofacial development showed CLL1 expression in the epithelium and mesenchyme of the palatal shelf and jaw in embryos at embryonic day (E) 18.5. Immunofluorescence revealed mandibular epithelial expression as early as E13.5, and showed coexpression between CLL1 and laminin, with CLL1 clearly visible in the basement membrane in the palatal area.
By FISH, Ohtani et al. (1999) mapped the COLEC10 gene to chromosome 8q23-q24.1.
Ohtani et al. (1999) found that a COLEC10 recombinant fusion protein lacking the collagen and N-terminal domains bound mannose weakly. It did not bind to mannan columns. An analysis of the saccharide specificities showed that COLEC10 has affinity for mannose, fucose, and galactose, with lower affinity for N-acetylglucosamine and lowest affinity for N-acetylgalactosamine.
Munye et al. (2017) investigated the ability of CLL1 to act as a chemoattractant for human cells. They observed that CLL1-containing discs showed extensive migration and invasion of HeLa cells into the discs.
In 2 Pakistani sibs and an unrelated Pakistani patient with 3MC syndrome-3 (3MC3; 248340), Munye et al. (2017) identified compound heterozygosity for mutations in the COLEC10 gene (607620.0001-607620.0003).
In 2 Pakistani sibs and an unrelated Pakistani patient with 3MC syndrome-3 (3MC3; 248340), Munye et al. (2017) identified compound heterozygosity for mutations in the COLEC10 gene: the Pakistani brother and sister (family 19) had a c.25C-T transition (c.25C-T, NM_006438.4) in exon 1, resulting in an arg9-to-ter (R9X) substitution, and a 1-bp deletion (c.226delA; 607620.0002) in exon 3, causing a frameshift predicted to result in a premature termination codon (Gly77GlufsTer66). Their unaffected parents were each heterozygous for 1 of the mutations. The unrelated Pakistani female (family 25) was compound heterozygous for the R9X mutation and a c.528C-G transversion in exon 6, resulting in a cys176-to-trp (C176W; 607620.0003) substitution within the CRD domain. Her unaffected parents and sibs were unavailable for testing. The 1-bp deletion was not found in the ExAC database, whereas the C176W and R9X mutations were present at frequencies of 1 in 120,850 and 4 in 121,220 chromosomes, respectively. In transfection studies using HeLa and HEK293 cells, no protein was detected by Western blot analysis with the R9X and Gly77GlufsTer66 mutants, suggesting that both transcripts undergo nonsense-mediated decay. In contrast, the C176W mutant was detected in cell lysates but not in the supernatant, indicating expression but not secretion. Quantitative ELISA showed higher levels of C176W mutant protein than wildtype in cell pellets, but severely reduced levels of the mutant compared to wildtype in supernatant analysis, consistent with impaired secretion of C176W protein.
For discussion of the 1-bp deletion (c.226delA, NM_006438.4) in exon 3 of the COLEC10 gene, causing a frameshift predicted to result in a premature termination codon (Gly77GlufsTer66), that was found in compound heterozygous state in a Pakistani brother and sister with 3MC syndrome-3 (3MC3; 248340) by Munye et al. (2017), see 607620.0001.
For discussion of the c.528C-G transversion (c.528C-G, NM_006438.4) in exon 6 of the COLEC10 gene, resulting in a cys176-to-trp (C176W) substitution, that was found in compound heterozygous state in a Pakistani female patient (family 25) with 3MC syndrome-3 (3MC3; 248340) by Munye et al. (2017), see 607620.0001.
Munye, M. M., Diaz-Font, A., Ocaka, L., Henriksen, M. L., Lees, M., Brady, A., Jenkins, D., Morton, J., Hansen, S. W., Bacchelli, C., Beales, P. L., Hernandez-Hernandez, V. COLEC10 is mutated in 3MC patients and regulates early craniofacial development. PLoS Genet. 13: e1006679, 2017. Note: Electronic Article. [PubMed: 28301481] [Full Text: https://doi.org/10.1371/journal.pgen.1006679]
Ohtani, K., Suzuki, Y., Eda, S., Kawai, T., Kase, T., Yamazaki, H., Shimada, T., Keshi, H., Sakai, Y., Fukuoh, A., Sakamoto, T., Wakamiya, N. Molecular cloning of a novel human collectin from liver (CL-L1). J. Biol. Chem. 274: 13681-13689, 1999. [PubMed: 10224141] [Full Text: https://doi.org/10.1074/jbc.274.19.13681]