ArticleAmerican journal of human genetics2021
Deleterious variants in X-linked CFAP47 induce asthenoteratozoospermia and primary male infertility.
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Article in American journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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74 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.
- A systematic review of the validated monogenic causes of human male infertility: 2020 update and a discussion of emerging gene-disease relationships.Human reproduction update · 2021Pooled it
- Molecular interplay between sperm and oocyte: a narrative review.Human reproduction update · 2026Review
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- Identification of biomarkers related to amino acid metabolism in nonobstructive azoospermia by bioinformatics.Medicine · 2026Article
- Deficiency of primate-specific TFDP3 causes male infertility with oligoasthenoteratozoospermia in humans and cynomolgus monkeys.Science China. Life sciences · 2026Article
- Investigating the time-dependent withdrawal effects of sofosbuvir and/or ribavirin on male mice: a histological and histophotometrical approach.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Novel mutations in FSIP2 cause male infertility through multiple morphological abnormalities of the sperm flagella.Asian journal of andrology · 2026Article
- ZFP36 inhibits the pro-apoptotic effects of transforming growth factor β1 on mitral valve interstitial cells via the GTP-binding protein 6 pathway in mitral valve prolapse.Experimental physiology · 2026Article
- CFAP251 Deficiency Induces Male Infertility and PCD-like Ciliary Defects by Disrupting TUBB4B and SLC25A4 Recruitment in Humans and Mice.International journal of biological sciences · 2026Article
- CAPZA1 deficiency disrupts sperm flagellar structure and motility, potentially involving the p300/SLC7A11 pathway.Frontiers in endocrinology · 2026Article
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- Identification of epileptic hippocampal sclerosis related genes through bulk and single-nucleus RNA sequencing datasets.Cellular and molecular life sciences : CMLS · 2025Article
- Novel DNAH17 Splice-Site Mutations Truncating the AAA6 Domain Cause Asthenozoospermia with MMAF.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Novel biallelic HFM1 variants cause severe oligozoospermia with favorable intracytoplasmic sperm injection outcome.Asian journal of andrology · 2025Article
- Genomic insights into the population structure and adaptive variation of Mullus barbatus in the Mediterranean Sea.BMC ecology and evolution · 2025Article
- The TEX44-CPT1B axis regulates mitochondrial sheath assembly and fatty acid oxidation in sperm.Nature communications · 2025Article
- Establishing the causative link between CFAP221 variants and asthenoteratozoospermia in humans.Journal of assisted reproduction and genetics · 2025Article
- Function of manchette and intra-manchette transport in spermatogenesis and male fertility.Cell communication and signaling : CCS · 2025Review
- Novel variants of FSIP2 and SPEF2 cause varying degrees of spermatozoa damage in MMAF patients and favorable ART outcomes.Journal of assisted reproduction and genetics · 2025Article
- Homozygous deleterious variants in MYCBPAP induce asthenoteratozoospermia involving abnormal acrosome biogenesis, manchette structure and sperm tail assembly in humans and mice.Science China. Life sciences · 2025Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 11 institutions in 4 countries.
Chunyu LiuObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
Chaofeng TuInstitute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410000, China; Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha 410000, China; Clinical Research Center for Reproduction and Genetics in Hunan Province, Changsha 410000, China.
Lingbo WangObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China; State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Huan WuReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei 230032, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, Hefei 230032, China.
Brendan J HoustonSchool of Biological Sciences, Monash University, Clayton, VIC 3800, Australia; School of BioSciences, The University of Melbourne, Parkville, VIC 3010, Australia.
Francesco K MastrorosaBiosciences Institute, Faculty of Medical Sciences, Newcastle University, NE2 4HH Newcastle upon Tyne, UK.
Wen ZhangFudan University Pudong Medical Center, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Department of Systems Biology for Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Ying ShenDepartment of Obstetrics/Gynecology, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Jiaxiong WangState Key Laboratory of Reproductive Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215002, China; Suzhou Municipal Hospital, Suzhou 215002, China.
Shixiong TianObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
Lanlan MengReproductive and Genetic Hospital of CITIC-Xiangya, Changsha 410000, China.
Jiangshan CongObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
Shenmin YangState Key Laboratory of Reproductive Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215002, China; Suzhou Municipal Hospital, Suzhou 215002, China.
Yiwen JiangObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China.
Shuyan TangObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
Yuyan ZengObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China.
Mingrong LvReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei 230032, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, Hefei 230032, China.
Ge LinInstitute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410000, China; Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha 410000, China; Clinical Research Center for Reproduction and Genetics in Hunan Province, Changsha 410000, China.
Jinsong LiState Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Hexige SaiyinObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China.
Xiaojin HeReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei 230032, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, Hefei 230032, China.
Li JinObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China.
Aminata TouréTeam Genetics Epigenetics and Therapies of Infertility, Institute for Advance Biosciences, Grenoble Alpes University, INSERM U1209, Centre National de la Recherche Scientifique UMR 5309, Grenoble 38000, France.
Pierre F RayTeam Genetics Epigenetics and Therapies of Infertility, Institute for Advance Biosciences, Grenoble Alpes University, INSERM U1209, Centre National de la Recherche Scientifique UMR 5309, Grenoble 38000, France; UM de genetique de l'infertilite et de diagnostic pre-implantatoire, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble 38000, France.
Joris A VeltmanBiosciences Institute, Faculty of Medical Sciences, Newcastle University, NE2 4HH Newcastle upon Tyne, UK.
Qinghua ShiThe First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei 230027, China.
Moira K O'BryanSchool of Biological Sciences, Monash University, Clayton, VIC 3800, Australia; School of BioSciences, The University of Melbourne, Parkville, VIC 3010, Australia.
Yunxia CaoReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei 230032, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, Hefei 230032, China.
Yue-Qiu TanInstitute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410000, China; Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha 410000, China; Clinical Research Center for Reproduction and Genetics in Hunan Province, Changsha 410000, China. Electronic address: tanyueqiu@csu.edu.cn.
Feng ZhangObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China. Electronic address: zhangfeng@fudan.edu.cn.
Fudan University · CNMinistry of Education of the People's Republic of China · CNCentral South University · CNInserm · FRNewcastle University · GBSuzhou Municipal Hospital · CNThe University of Melbourne · AUCenter for Excellence in Molecular Cell Science · CNReproductive & Genetic Hospital CITIC-Xiangya · CNSichuan University · CNUniversity of Science and Technology of China · CN
Funding
Wellcome Trust 209451/Z/17/Z
Abstract
Asthenoteratozoospermia characterized by multiple morphological abnormalities of the flagella (MMAF) has been identified as a sub-type of male infertility. Recent progress has identified several MMAF-associated genes with an autosomal recessive inheritance in human affected individuals, but the etiology in approximately 40% of affected individuals remains unknown. Here, we conducted whole-exome sequencing (WES) and identified hemizygous missense variants in the X-linked CFAP47 in three unrelated Chinese individuals with MMAF. These three CFAP47 variants were absent in human control population genome databases and were predicted to be deleterious by multiple bioinformatic tools. CFAP47 encodes a cilia- and flagella-associated protein that is highly expressed in testis. Immunoblotting and immunofluorescence assays revealed obviously reduced levels of CFAP47 in spermatozoa from all three men harboring deleterious missense variants of CFAP47. Furthermore, WES data from an additional cohort of severe asthenoteratozoospermic men originating from Australia permitted the identification of a hemizygous Xp21.1 deletion removing the entire CFAP47 gene. All men harboring hemizygous CFAP47 variants displayed typical MMAF phenotypes. We also generated a Cfap47-mutated mouse model, the adult males of which were sterile and presented with reduced sperm motility and abnormal flagellar morphology and movement. However, fertility could be rescued by the use of intra-cytoplasmic sperm injections (ICSIs). Altogether, our experimental observations in humans and mice demonstrate that hemizygous mutations in CFAP47 can induce X-linked MMAF and asthenoteratozoospermia, for which good ICSI prognosis is suggested. These findings will provide important guidance for genetic counseling and assisted reproduction treatments.
Indexed as
AnimalsAsthenozoospermiaCohort StudiesExome SequencingFemaleGene DeletionGenes, X-LinkedHemizygoteHumansInfertility, MaleMaleMiceMice, Inbred C57BLMutationMutation, MissensePedigreeCFAP47CFAP65ciliaflagellumICSImale infertilitymiceMMAFsperm
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