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Keratin genes comprise the largest subset of IntFil genes. Whereas the first keratin gene appeared in sponge, and three genes in arthropods, more rapid increases in keratin genes occurred in lungfish and amphibian genomes, concomitant with land animal-sea animal divergence (~\u2009440 to 410 million years ago). Human, mouse and zebrafish genomes contain 18, 17 and 24 non-keratin IntFil genes, respectively. Human has 27 of 28 type I \u201cacidic\u201d keratin genes clustered at chromosome (Chr) 17q21.2, and all 26 type II \u201cbasic\u201d keratin genes clustered at Chr 12q13.13. Mouse has 27 of 28 type I keratin genes clustered on Chr 11, and all 26 type II clustered on Chr 15. Zebrafish has 18 type I keratin genes scattered on five chromosomes, and 3 type II keratin genes on two chromosomes. Types I and II keratin clusters\u2014reflecting evolutionary blooms of keratin genes along one chromosomal segment\u2014are found in all land animal genomes examined, but not fishes; such rapid gene expansions likely reflect sudden requirements for many novel paralogous proteins having divergent functions to enhance species survival following sea-to-land transition. Using data from the Genotype-Tissue Expression (GTEx) project, tissue-specific keratin expression throughout the human body was reconstructed. Clustering of gene expression patterns revealed similarities in tissue-specific expression patterns for previously described \u201ckeratin pairs\u201d (i.e., KRT1\/KRT10, KRT8\/KRT18, KRT5\/KRT14, KRT6\/KRT16 and KRT6\/KRT17 proteins). The ClinVar database currently lists 26 human disease-causing variants within the various domains of keratin proteins.<\/jats:p>","DOI":"10.1186\/s40246-021-00374-9","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T05:03:46Z","timestamp":1641445426000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["Update of the keratin gene family: evolution, tissue-specific expression patterns, and relevance to clinical disorders"],"prefix":"10.1186","volume":"16","author":[{"given":"Minh","family":"Ho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey Nicholas","family":"Fisk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel W.","family":"Nebert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elspeth A.","family":"Bruford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasilis","family":"Vasiliou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4011-8308","authenticated-orcid":false,"given":"Christopher G.","family":"Bunick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"key":"374_CR1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1098\/rsta.1932.0003","volume":"230","author":"WTAA Street","year":"1931","unstructured":"Street WTAA. 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