Alternative titles; symbols
HGNC Approved Gene Symbol: KRT75
Cytogenetic location: 12q13.13 Genomic coordinates (GRCh38): 12:52,424,070-52,434,371 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 12q13.13 | {Pseudofolliculitis barbae, susceptibility to} | 612318 | 3 |
By 5-prime and 3-prime RACE of anagen hair follicle cDNA, Winter et al. (1998) cloned K6HF. The deduced 551-amino acid protein shares about 80% homology with cytokeratin KRT5 (148040). In situ hybridization and indirect immunofluorescence localization showed that K6HF was expressed exclusively in the companion layer of the hair follicle before KRT17 (148069) and KRT16 (148067).
Wojcik et al. (2001) cloned mouse K6hf. The deduced 551-amino acid protein shares 84.8% identity with human K6HF.
Wojcik et al. (2001) found that K6hf assembled into a keratin network following transfection of kangaroo rat kidney epithelial cells.
Rogers et al. (2000) determined that the K6HF gene spans 17.4 kb.
By screening an arrayed PAC DNA library, Rogers et al. (2000) mapped the K6HF gene to a region of chromosome 12q13 that flanks a series of hair keratin genes and pseudogenes.
Winter et al. (2004) identified a nonsynonymous SNP in the KRT75 gene (A12T; 609025.0001) that was significantly associated with the development of pseudofolliculitis barbae (612318).
In 2 affected members of a Caucasian family with pseudofolliculitis barbae (612318), Winter et al. (2004) identified a heterozygous G-to-A transition in the KRT75 gene, resulting in an ala12-to-thr (A12T) substitution in the 1A alpha-helical subdomain of KRT75. The mutation was also present in an unaffected female relative who had straight hair and did not shave regularly. In a larger group of 200 individuals, Winter et al. (2004) found that the A12T SNP was present in 9% of individuals without the disorder and 35% with the disorder, which was a significant association (p less than 6 x 10(-6)). The incidence of the A12T substitution in the investigated population was approximately 3 times higher in African Americans compared to Caucasians (36.7% vs 10.9%). Computer modeling showed that the A12T substitution occurred in an external position on the surface of the coiled-coil domain and did not affected the ability of alpha-helical structures to assemble in parallel. However, in vitro expression studies showed that the variant was disruptive at later stages, compromising the aggregation of keratin molecules into intermediate filaments. Winter et al. (2004) postulated that the A12T SNP destabilizes the mechanical integrity of companion cells in the hair shaft, which may compromise the ability of the shaft to move within the skin surface.
Rogers, M. A., Winter, H., Langbein, L., Wolf, C., Schweizer, J. Characterization of a 300 kbp region of human DNA containing the type II hair keratin gene domain. J. Invest. Derm. 114: 464-472, 2000. [PubMed: 10692104] [Full Text: https://doi.org/10.1046/j.1523-1747.2000.00910.x]
Winter, H., Langbein, L., Praetzel, S., Jacobs, M., Rogers, M. A., Leigh, I. M., Tidman, N., Schweizer, J. A novel human type II cytokeratin, K6hf, specifically expressed in the companion layer of the hair follicle. J. Invest. Derm. 111: 955-962, 1998. [PubMed: 9856802] [Full Text: https://doi.org/10.1046/j.1523-1747.1998.00456.x]
Winter, H., Schissel, D., Parry, D. A. D., Smith, T. A., Liovic, M., Lane, E. B., Edler, L., Langbein, L., Jave-Suarez, L. F., Rogers, M. A., Wilde, J., Peters, G., Schweizer, J. An unusual ala12thr polymorphism in the 1A alpha-helical segment of the companion layer-specific keratin K6hf: evidence for a risk factor in the etiology of the common hair disorder pseudofolliculitis barbae. J. Invest. Derm. 122: 652-657, 2004. [PubMed: 15086549] [Full Text: https://doi.org/10.1111/j.0022-202X.2004.22309.x]
Wojcik, S. M., Longley, M. A., Roop, D. R. Discovery of a novel murine keratin 6 (K6) isoform explains the absence of hair and nail defects in mice deficient for K6a and K6b. J. Cell Biol. 154: 619-630, 2001. [PubMed: 11489919] [Full Text: https://doi.org/10.1083/jcb.200102079]