{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T22:20:49Z","timestamp":1780093249448,"version":"3.54.0"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T00:00:00Z","timestamp":1657238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["DTS18\/00101"],"award-info":[{"award-number":["DTS18\/00101"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2017SGR191"],"award-info":[{"award-number":["2017SGR191"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Previous studies in animal models evidenced that genetic mutations of <jats:italic>KATNAL1<\/jats:italic>, resulting in dysfunction of its encoded protein, lead to male infertility through disruption of microtubule remodelling and premature germ cell exfoliation. Subsequent studies in humans also suggested a possible role of <jats:italic>KATNAL1<\/jats:italic> single\u2010nucleotide polymorphisms in the development of male infertility as a consequence of severe spermatogenic failure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The main objective of the present study is to evaluate the effect of the common genetic variation of <jats:italic>KATNAL1<\/jats:italic> in a large and phenotypically well\u2010characterised cohort of infertile men because of severe spermatogenic failure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>A total of 715 infertile men because of severe spermatogenic failure, including 210 severe oligospermia and 505 non\u2010obstructive azoospermia patients, as well as 1058 unaffected controls were genotyped for three <jats:italic>KATNAL1<\/jats:italic> single\u2010nucleotide polymorphism taggers (rs2077011, rs7338931 and rs2149971). Case\u2013control association analyses by logistic regression assuming different models and in silico functional characterisation of risk variants were conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetic associations were observed between the three analysed taggers and different severe spermatogenic failure groups. However, in all cases, the haplotype model (rs2077011*C | rs7338931*T | rs2149971*A) better explained the observed associations than the three risk alleles independently. This haplotype was associated with non\u2010obstructive azoospermia (adjusted <jats:italic>p<\/jats:italic>\u00a0=\u00a04.96E\u201002, odds ratio\u00a0=\u00a02.97), Sertoli\u2010cell only syndrome (adjusted <jats:italic>p<\/jats:italic>\u00a0=\u00a02.83E\u201002, odds ratio\u00a0=\u00a05.16) and testicular sperm extraction unsuccessful outcomes (adjusted <jats:italic>p<\/jats:italic>\u00a0=\u00a08.99E\u201004, odds ratio\u00a0=\u00a06.13). The in silico analyses indicated that the effect on severe spermatogenic failure predisposition could be because of an alteration of the <jats:italic>KATNAL1<\/jats:italic> splicing pattern.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Specific allelic combinations of <jats:italic>KATNAL1<\/jats:italic> genetic polymorphisms may confer a risk of developing severe male infertility phenotypes by favouring the overrepresentation of a short non\u2010functional transcript isoform in the testis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13221","type":"journal-article","created":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T04:54:50Z","timestamp":1656219290000},"page":"1339-1350","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Common genetic variation in <i>KATNAL1<\/i> non\u2010coding regions is involved in the susceptibility to severe phenotypes of male infertility"],"prefix":"10.1111","volume":"10","author":[{"given":"Miriam","family":"Cerv\u00e1n\u2010Mart\u00edn","sequence":"first","affiliation":[{"name":"Departamento de Gen\u00e9tica e Instituto de Biotecnolog\u00eda, Centro de Investigaci\u00f3n Biom\u00e9dica Universidad de Granada  Granada Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs. 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