{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:49:12Z","timestamp":1791978552870,"version":"4.4.0"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["FLAGEL\u2010OME ANR\u201019\u2010CE17\u20100014"],"award-info":[{"award-number":["FLAGEL\u2010OME ANR\u201019\u2010CE17\u20100014"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["MASFLAGELLA ANR\u201014\u2010CE15\u20100002"],"award-info":[{"award-number":["MASFLAGELLA ANR\u201014\u2010CE15\u20100002"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005413","name":"Universit\u00e9 Paris Descartes","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005413","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Asthenozoospermia, defined by the absence or reduction of sperm motility, constitutes the most frequent cause of human male infertility. This pathological condition is caused by morphological and\/or functional defects of the sperm flagellum, which preclude proper sperm progression. While in the last decade many causal genes were identified for asthenozoospermia associated with severe sperm flagellar defects, the causes of purely functional asthenozoospermia are still poorly defined. We describe here the case of an infertile man, displaying asthenozoospermia without major morphological flagellar anomalies and carrying a homozygous splicing mutation in\n                    <jats:italic>SLC9C1<\/jats:italic>\n                    (\n                    <jats:italic>sNHE<\/jats:italic>\n                    ), which we identified by whole\u2010exome sequencing.\n                    <jats:italic>SLC9C1<\/jats:italic>\n                    encodes a sperm\u2010specific sodium\/proton exchanger, which in mouse regulates pH homeostasis and interacts with the soluble adenylyl cyclase (sAC), a key regulator of the signalling pathways involved in sperm motility and capacitation. We demonstrate by means of RT\u2010PCR, immunodetection and immunofluorescence assays on patient's semen samples that the homozygous splicing mutation (\n                    <jats:italic>c.2748\u2009+\u20092\u2009T\u2009&gt;\u2009C<\/jats:italic>\n                    ) leads to in\u2010frame exon skipping resulting in a deletion in the cyclic nucleotide\u2010binding domain of the protein. Our work shows that in human, similar to mouse, SLC9C1 is required for sperm motility. Overall, we establish a homozygous truncating mutation in\n                    <jats:italic>SLC9C1<\/jats:italic>\n                    as a novel cause of human asthenozoospermia and infertility.\n                  <\/jats:p>","DOI":"10.1111\/cge.13927","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T01:36:20Z","timestamp":1611020180000},"page":"684-693","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["The sodium\/proton exchanger\n                    <scp>SLC9C1<\/scp>\n                    (\n                    <scp>sNHE<\/scp>\n                    ) is essential for human sperm motility and fertility"],"prefix":"10.1111","volume":"99","author":[{"given":"Emma","family":"Cavarocchi","sequence":"first","affiliation":[{"name":"Institut Cochin, INSERM, CNRS Universit\u00e9 de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie","family":"Whitfield","sequence":"additional","affiliation":[{"name":"Institut Cochin, INSERM, CNRS Universit\u00e9 de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Chargui","sequence":"additional","affiliation":[{"name":"Laboratoire d'Histologie Embryologie \u2010 Biologie de la Reproduction \u2010 CECOS Groupe Hospitalier Universitaire Paris Centre Assistance Publique\u2010H\u00f4pitaux de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Stouvenel","sequence":"additional","affiliation":[{"name":"Institut Cochin, INSERM, CNRS Universit\u00e9 de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Lor\u00e8s","sequence":"additional","affiliation":[{"name":"Institut Cochin, INSERM, CNRS Universit\u00e9 de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8873-8098","authenticated-orcid":false,"given":"Charles","family":"Coutton","sequence":"additional","affiliation":[{"name":"Institut pour l'avanc\u00e9e des Biosciences, INSERM, CNRS Universit\u00e9 Grenoble Alpes  Grenoble France"},{"name":"CHU Grenoble Alpes UM de G\u00e9n\u00e9tique Chromosomique  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Arnoult","sequence":"additional","affiliation":[{"name":"Institut pour l'avanc\u00e9e des Biosciences, INSERM, CNRS Universit\u00e9 Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Santulli","sequence":"additional","affiliation":[{"name":"Service de Chirurgie Gyn\u00e9cologie Obst\u00e9trique 2 et M\u00e9decine de la Reproduction, Groupe Hospitalier Universitaire Paris Centre Assistance Publique\u2010H\u00f4pitaux de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Patrat","sequence":"additional","affiliation":[{"name":"Institut Cochin, INSERM, CNRS Universit\u00e9 de Paris  Paris France"},{"name":"Laboratoire d'Histologie Embryologie \u2010 Biologie de la Reproduction \u2010 CECOS Groupe Hospitalier Universitaire Paris Centre Assistance Publique\u2010H\u00f4pitaux de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Thierry\u2010Mieg","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes CNRS, TIMC\u2010IMAG\/BCM  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1544-7449","authenticated-orcid":false,"given":"Pierre F.","family":"Ray","sequence":"additional","affiliation":[{"name":"Institut pour l'avanc\u00e9e des Biosciences, INSERM, CNRS Universit\u00e9 Grenoble Alpes  Grenoble France"},{"name":"CHU de Grenoble UM GI\u2010DPI  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Dulioust","sequence":"additional","affiliation":[{"name":"Institut Cochin, INSERM, CNRS Universit\u00e9 de Paris  Paris France"},{"name":"Laboratoire d'Histologie Embryologie \u2010 Biologie de la Reproduction \u2010 CECOS Groupe Hospitalier Universitaire Paris Centre Assistance Publique\u2010H\u00f4pitaux de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5629-849X","authenticated-orcid":false,"given":"Aminata","family":"Tour\u00e9","sequence":"additional","affiliation":[{"name":"Institut pour l'avanc\u00e9e des Biosciences, INSERM, CNRS Universit\u00e9 Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14647273.2018.1504325"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)59482-5"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0272.2006.00711.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2005.12.042"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12610-019-0083-9"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-020-02113-x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm117"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22028"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep37836"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12905"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2019.00230"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmz032"},{"key":"e_1_2_9_14_1","first-page":"2","article-title":"Signaling mechanisms in mammalian sperm motility","volume":"96","author":"Freitas MJ","year":"2017","journal-title":"Biol Reprod"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2164\/jandrol.111.015552"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/aja.2010.69"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2019.00341"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-013-1408-8"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmp048"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dev251"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dey264"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2019-106775"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.10.007"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/der037"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2012.12.008"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1072"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05253-x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611296104"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.276.4.C788"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.65"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-017-0898-2"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2020.01.015"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.05.100"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.114.118331"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.607556"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.12.053"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP273189"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40851-019-0141-3"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deg204"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200991"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.03.016"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-14606-3"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0272.2010.01101.x"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv362"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2009.6"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13927","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.13927","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13927","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T10:06:58Z","timestamp":1693562818000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.13927"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,25]]},"references-count":44,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1111\/cge.13927"],"URL":"https:\/\/doi.org\/10.1111\/cge.13927","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.13927\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13927\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13927\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13927\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13927\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13927\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13927\/v2\/review2","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,25]]},"assertion":[{"value":"2020-10-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}