Alternative titles; symbols
HGNC Approved Gene Symbol: COL14A1
Cytogenetic location: 8q24.12 Genomic coordinates (GRCh38): 8:120,124,454-120,373,573 (from NCBI)
Type XIV collagen is a fibril-associated collagen with an interrupted triple helix. It interacts with the fibril surface and regulates fibrillogenesis (Ansorge et al., 2009).
Schuppan et al. (1990) isolated undulin, a large glycoprotein of the interstitial extracellular matrix, from skin and placenta. In SDS-polyacrylamide gels, undulin had a molecular mass above 1,000 kD; under reducing conditions, it migrated as 270-, 190-, and 180-kD polypeptides. Undulin was restricted to dense and soft connective tissues and was associated with mature collagen fibrils.
Dublet and van der Rest (1991) extracted a homotrimeric collagen molecule, type XIV collagen, from fetal bovine skin and tendon. They demonstrated that collagen XIV has a triple helical disulfide-bonded domain homologous to type IX (e.g., 120210) and type XII (e.g., 120320) collagens.
By immunoscreening a human placenta cDNA expression library with antibodies against monkey undulin, Just et al. (1991) isolated 2 partial cDNAs, called UN1 and UN2, which encode the C-terminal portions of 2 undulin isoforms. The sequences of UN1 and UN2 are partly identical, and the authors suggested that they represent differentially spliced undulin transcripts. Northern blot analysis of human rhabdomyosarcoma cell poly(A) RNA using a probe specific for UN1 detected approximately 4.2-, 6.5-, and 8.5-kb transcripts; a probe specific for UN2 detected a single, approximately 5-kb transcript. The deduced polypeptides contain a differentially spliced von Willebrand factor (VWF; 613160) A domain and the type III homology domains found in fibronectin (135600) and tenascin (187380). Whereas UN1 has 7 complete and 1 truncated type III homology domains followed by a short proline-rich C-terminal segment, UN2 has 2 complete and 1 incomplete type III homologies followed by a unique acidic C-terminal domain. The authors stated that the mRNAs related to UN1 likely encode the major chains of the undulin molecule.
To complete the partial human undulin cDNA sequences determined by Just et al. (1991), Bauer et al. (1997) isolated additional undulin cDNAs by 5-prime RACE, 3-prime RACE, and library screenings (GenBank Y11709, Y11710, Y11711). Beginning at the N terminus, the predicted 1,780-amino acid undulin protein contains a putative signal peptide, followed immediately by a fibronectin type III domain, a VWF A domain, 7 fibronectin type III domains, a second VWF A domain, and several collagenous and noncollagenous domains in the C-terminal region. The authors identified 2 additional 3-prime cDNAs; one of these may represent usage of an alternative polyadenylation signal, and the other encodes a variant C-terminal noncollagenous domain. Bauer et al. (1997) stated that undulin is identical to collagen XIV. The human undulin proteins are 75% identical to chicken collagen XIV.
By fluorescence in situ hybridization, Schnittger et al. (1995) assigned the UND gene to chromosome 8q23.
In 8 affected and 2 unaffected members of a 4-generation Chinese family with autosomal dominant punctate palmoplantar keratoderma (PPKP) mapping to chromosome 8q24.13-q24.21 (PPKP1B; 614936), Guo et al. (2012) identified a possibly causative heterozygous missense mutation in the COL14A1 gene (P1502L; 120324.0001).
Ansorge et al. (2009) found that Col14a1 -/- mice were born at the expected mendelian ratio and developed normally. Newborn wildtype mice expressed high levels of Col14a1 mRNA and protein in skin and tendon, and expression of Col14a1 in flexor digitorum longus tendon correlated with the formation of mature fibrils from fibril intermediates. Expression of Col14a1 in both skin and tendon decreased with maturity and was not detected in adult wildtype tendon. Skin of both newborn and adult Col14a1 -/- mice appeared normal, but mutant skin showed altered biomechanical properties, with reduced maximum stress tolerance and decreased modulus of elasticity. Tendons of newborn Col14a1 -/- mice appeared disorganized with abnormal fibril and fiber assembly, and biomechanical analysis showed reduced maximum load, stiffness, and modulus of elasticity compared with wildtype tendon. However, tendons of adult Col14a1 -/- mice appeared and functioned normally. Ansorge et al. (2009) concluded that COL14A1 has a regulatory role in the early stages of collagen fibrillogenesis.
This variant is classified as a variant of unknown significance because its contribution to punctate palmoplantar keratoderma type IB (PPKP1B; 614936) has not been confirmed.
In 8 affected and 2 unaffected members of a 4-generation Chinese family with autosomal dominant punctate palmoplantar keratoderma mapping to chromosome 8q24, previously studied by Zhang et al. (2004), Guo et al. (2012) identified heterozygosity for a 4504C-T transition in exon 37 of the COL14A1 gene, resulting in a pro1502-to-leu (P1502L) substitution at a highly conserved residue. The mutation was not found in 676 unrelated ethnically and geographically matched controls, or in 718 unrelated ethnically and geographically matched patients with other diseases. The mutation-positive but unaffected family members were a 15-year-old boy and his uncle. Guo et al. (2012) suggested that COL14A1 might be a causal gene for PPKP, noting that at 15 years of age, the boy was at the lower limit for average age at onset of disease in this family and might yet develop symptoms.
Ansorge, H. L., Meng, X., Zhang, G., Veit, G., Sun, M., Klement, J. F., Beason, D. P., Soslowsky, L. J., Koch, M., Birk, D. E. Type XIV collagen regulates fibrillogenesis: premature collagen fibril growth and tissue dysfunction in null mice. J. Biol. Chem. 284: 8427-8438, 2009. [PubMed: 19136672] [Full Text: https://doi.org/10.1074/jbc.M805582200]
Bauer, M., Dieterich, W., Ehnis, T., Schuppan, D. Complete primary structure of human collagen type XIV (undulin). Biochim. Biophys. Acta 1354: 183-188, 1997. [PubMed: 9427527] [Full Text: https://doi.org/10.1016/s0167-4781(97)00131-0]
Dublet, B., van der Rest, M. Type XIV collagen, a new homotrimeric molecule extracted from fetal bovine skin and tendon, with a triple helical disulfide-bonded domain homologous to type IX and type XII collagens. J. Biol. Chem. 266: 6853-6858, 1991. [PubMed: 2016301]
Guo, B.-R., Zhang, X., Chen, G., Zhang, J.-G., Sun, L.-D., Du, W., Zhang, Q., Cui, Y., Zhu, J., Tang, X.-F., Xiao, R., Liu, Y., and 17 others. Exome sequencing identifies a COL14A1 mutation in a large Chinese pedigree with punctate palmoplantar keratoderma. J. Med. Genet. 49: 563-568, 2012. [PubMed: 22972947] [Full Text: https://doi.org/10.1136/jmedgenet-2012-100868]
Just, M., Herbst, H., Hummel, M., Durkop, H., Tripier, D., Stein, H., Schuppan, D. Undulin is a novel member of the fibronectin-tenascin family of extracellular matrix glycoproteins. J. Biol. Chem. 266: 17326-17332, 1991. [PubMed: 1716629]
Schnittger, S., Herbst, H., Schuppan, D., Dannenberg, C., Bauer, M., Fonatsch, C. Localization of the undulin gene (UND) to human chromosome band 8q23. Cytogenet. Cell Genet. 68: 233-234, 1995. [PubMed: 7842743] [Full Text: https://doi.org/10.1159/000133920]
Schuppan, D., Cantaluppi, M. C., Becker, J., Veit, A., Bunte, T., Troyer, D., Schuppan, F., Schmid, M., Ackermann, R., Hahn, E. G. Undulin, an extracellular matrix glycoprotein associated with collagen fibrils. J. Biol. Chem. 265: 8823-8832, 1990. [PubMed: 2187872]
Zhang, X.-J., Li, M., Gao, T.-W., He, P.-P., Wei, S.-C., Liu, J.-B., Li, C.-R., Cui, Y., Yang, S., Yuan, W.-T., Li, C.-Y., Liu, Y.-F., Xu, S.-J., Huang, W. Identification of a locus for punctate palmoplantar keratodermas at chromosome 8q24.13-8q24.21. J. Invest. Derm. 122: 1121-1125, 2004. [PubMed: 15140213] [Full Text: https://doi.org/10.1111/j.0022-202X.2004.22507.x]