Alternative titles; symbols
HGNC Approved Gene Symbol: MUC7
Cytogenetic location: 4q13.3 Genomic coordinates (GRCh38): 4:70,430,492-70,482,997 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 4q13.3 | {Asthma, protection against} | 600807 | Autosomal dominant | 3 |
The MUC7 gene encodes a small salivary mucin, which is thought to function in a protective capacity by promoting the clearance of bacteria in the oral cavity and to aid in mastication, speech, and swallowing (Kirkbride et al., 2001).
Bobek et al. (1993) described the isolation and characterization of overlapping cDNA clones that code for the low molecular weight glycoprotein core. Sequencing revealed a translated region of 1,131 nucleotides encoding a protein of 377 amino acid residues with a molecular mass of 39 kD. No sequence homology with any other human or animal mucins, and no significant homology to any other proteins was found. The mRNA was about 2.5 kb long, and its expression appeared to be species-, tissue-, and cell-specific. They proposed the designation MUC7 for the gene in accordance with the other mucin genes previously cloned, MUC1-MUC6.
Bobek et al. (1996) found that the MUC7 gene spans approximately 10 kb and comprises 3 exons and 2 introns. Intron 1 is approximately 1.7 kb long and is located in the 5-prime untranslated region of the MUC7 cDNA. Intron 2 spans approximately 6 kb and is located close to the boundary of the putative liter peptide and secreted protein. The entire region encoding the secreted peptide is located on exon 3, spanning approximately 2.2 kb.
By PCR analysis of a human/hamster somatic cell hybrid panel and by fluorescence in situ hybridization, Bobek et al. (1996) mapped the MUC7 gene to chromosome 4q13-q21.
Kirkbride et al. (2001) studied the allelic distribution of the MUC7 VNTR (158375.0001) in different ethnic backgrounds and identified the MUC7*5 allele at a lower frequency in asthmatics compared to nonasthmatic controls.
Kirkbride et al. (2001) noted that the most common allele of the variable number tandem repeat (VNTR) of the MUC7 gene comprises 6 tandem repeats, each repeat consisting of 69 nucleotides. These repeats are very similar but not identical, incorporating between 1 and 7 nucleotide substitutions between them. In a large cohort of 375 individuals from a variety of ethnic backgrounds, Kirkbride et al. (2001) examined the allelic distribution of the VNTR of the MUC7 gene. Three different alleles were detected, MUC7*6 being the most common in all populations studied, followed by MUC7*5, with frequency varying from 0.05 in Africans to 0.22 in East Asians. MUC7*8, a novel rare allele, was identified in 1 Northern European individual. Kirkbride et al. (2001) tested the MUC7 VNTR in a series of Northern European atopic individuals with and without associated asthma (600807). The MUC7*5 allele was rarer in the atopic asthmatics than in the atopic nonasthmatics. Comparison of all atopic individuals with all nonatopic showed no difference, while comparison of all asthmatic individuals with all nonasthmatic showed that the asthmatic group had reduced MUC7*5 frequency. The significantly lower frequency of the MUC7*5 allele in individuals with atopic asthma was explained by the possible association between alleles and different interactions with bacteria, since the glycosylated domain is thought to be responsible, at least in part, for the bacterial binding that allows bacteria to be cleared from the epithelial surfaces.
Rousseau et al. (2006) followed up on their earlier report that the MUC7*5 allele is less prevalent in patients with asthma, suggesting a protective role in respiratory function. They characterized additional variations within and in the vicinity of the MUC7 gene. Of 26 polymorphisms identified, 5 were located in transcribed regions. A subset of 8 polymorphisms was selected to represent the major haplotypes, and allelic association was studied in asthmatics and controls previously studied by Kirkbride et al. (2001). There was low haplotype diversity and strong association between each of the loci, and the MUC7*5-carrying haplotype was less frequent in asthmatics than controls. By genotype and haplotype analysis of the MRC National Survey of Health and Development 1946 longitudinal birth cohort, for whom developmental, environmental, and respiratory health data were available, Rousseau et al. (2006) showed that the MUC7*5-carrying haplotype was associated with higher forced expiratory volume in 1 second (FEV1) at age 53 years, reduced age-related decline of FEV1, and reduced incidence of wheeze.
Bobek, L. A., Liu, J., Sait, S. N. J., Shows, T. B., Bobek, Y. A., Levine, M. J. Structure and chromosomal localization of the human salivary mucin gene, MUC7. Genomics 31: 277-282, 1996. [PubMed: 8838308] [Full Text: https://doi.org/10.1006/geno.1996.0049]
Bobek, L. A., Tsai, H., Biesbrock, A. R., Levine, M. J. Molecular cloning, sequence, and specificity of expression of the gene encoding the low molecular weight human salivary mucin (MUC7). J. Biol. Chem. 268: 20563-20569, 1993. [PubMed: 7690757]
Kirkbride, H. J., Bolscher, J. G., Nazmi, K., Vinall, L. E., Nash, M. W., Moss, F. M., Mitchell, D. M., Swallow, D. M. Genetic polymorphism of MUC7: allele frequencies and association with asthma. Europ. J. Hum. Genet. 9: 347-354, 2001. [PubMed: 11378823] [Full Text: https://doi.org/10.1038/sj.ejhg.5200642]
Rousseau, K., Vinall, L. E., Butterworth, S. L., Hardy, R. J., Holloway, J., Wadsworth, M. E. J., Swallow, D. M. MUC7 haplotype analysis: results from a longitudinal birth cohort support protective effect of the MUC7*5 allele on respiratory function. Ann. Hum. Genet. 70: 417-427, 2006. [PubMed: 16759176] [Full Text: https://doi.org/10.1111/j.1469-1809.2006.00250.x]