TABLE 1.
Recently identified reproductive tract-specific genes with male infertility phenotypes in mice: potential non-hormonal male contraceptive drug targets.
| Gene Symbol (Mouse/Human) |
Drug Target Type |
Spermatogenic Site of Expression |
MW (kDa) | Reduced testis size in mouse |
|||||
| Mouse | Human | # TM | Secreted | Conditions underlying male infertility in mouse | References | ||||
| Asz1/ASZ1 | Unknown | Spermatogonia | 53 | 53.5 | 0 | No | increased hypomethylation of retrotransposons, germ cell loss due to apoptosis, Sertoli cell only phenotype | Yes | Ma et al., 2009 |
| Mov10l1/MOV10L1 | Enzyme | Spermatogonia | 132.8 | 135.3 | 0 | No | Abnormal spermatocyte morphology, arrest of male meiosis | Yes | Frost et al., 2010 |
| Scml2/SCML2 | Epigenetic | Spermatogonia | 80.1 | 77.3 | 0 | No | Abnormal spermiogenesis | Yes | Hasegawa et al., 2015 |
| Tex101/TEX101 | Unknown | Spermatogonia | 21.1 | 26.7 | 0 | No | Abnormal sperm physiology | No | Li et al., 2013 |
| 4930447C04Rik/C14orf39 | Unknown | Spermatocytes | 66.9 | 68.2 | 0 | No | Azoospermia | Yes | Gomez et al., 2016 |
| Boll/BOLL | Unknown | Spermatocytes | 30.9 | 31.3 | 0 | No | Azoospermia, abnormal male germ cell apoptosis, abnormal spermatogenesis | Yes | VanGompel and Xu, 2010 |
| Btbd18/BTBD18 | Unknown | Spermatocytes | 79.5 | 77.9 | 0 | No | Abnormal spermatid morphology, arrest of spermiogenesis | Yes | Zhou et al., 2017 |
| Ccdc155/CCDC155 | Unknown | Spermatocytes | 72.4 | 62.8 | 0 | No | Abnormal chromosomal synapsis, abnormal double-strand DNA break repair, abnormal meiotic attachment of telomere to nuclear envelope | Yes | Horn et al., 2013 |
| Ccdc63/CCDC63 | Unknown | Spermatocytes | 65.2 | 66.3 | 0 | No | Shortened sperm flagella | No | Young et al., 2015 |
| Cnbd2/CNBD2 | Unknown | Spermatocytes | 77.9 | 67.5 | 0 | No | Abnormal sperm midpiece morphology, abnormal sperm motility | Yes | Krahling et al., 2013 |
| Fbxo43/FBXO43 | Unknown | Spermatocytes | 71.2 | 78.4 | 0 | No | Arrest of male meiosis | Yes | Gopinathan et al., 2017 |
| Hfm1/HFM1 | Enzyme | Spermatocytes | 161.4 | 162.6 | 0 | No | Abnormal chiasmata formation, abnormal chromosomal synapsis, arrest of male meiosis | Yes | Guiraldelli et al., 2013 |
| Hormad2/HORMAD2 | Unknown | Spermatocytes | 34.8 | 35.3 | 0 | No | Abnormal chiasmata formation, arrest of spermatogenesis | Yes | Kogo et al., 2012a |
| Insl6/INSL6 | Unknown | Spermatocytes | 22.2 | 22.5 | 0 | Yes | Azoospermia, abnormal male germ cell morphology | Yes | Burnicka-Turek et al., 2009 |
| Ly6k/LY6K | Unknown | Spermatocytes | 11.7 | 14.2 | 0 | Yes | Abnormal sperm physiology | No | Fujihara et al., 2014 |
| Mcmdc2/MCMDC2 | Unknown | Spermatocytes | 76 | 76.2 | 0 | No | Abnormal double-strand DNA break repair, abnormal synaptonemal complex | Yes | Finsterbusch et al., 2016 |
| Meiob/MEIOB | Unknown | Spermatocytes | 53 | 49.3 | 0 | No | Abnormal double-strand DNA break repair, abnormal meiosis, arrest of spermatogenesis | Yes | Luo et al., 2013; Souquet et al., 2013 |
| Meioc/MEIOC | Unknown | Spermatocytes | 108.9 | 107.6 | 0 | No | Abnormal double-strand DNA break repair, abnormal synaptonemal complex | Yes | Abby et al., 2016 |
| Nup210l/NUP210L | Unknown | Spermatocytes | 205.1 | 206.6 | 1 | Yes | Abnormal acrosome morphology, abnormal sperm midpiece morphology | Unknown | Walters et al., 2009 |
| Pgk2/PGK2 | Kinase | Spermatocytes | 44.9 | 44.7 | 0 | No | Asthenozoospermia | No | Danshina et al., 2010 |
| Pih1h3b/PIH1D3 | Unknown | Spermatocytes | 24.5 | 24.1 | 0 | No | Abnormal sperm axoneme morphology, abnormal sperm flagellum morphology | Yes | Dong et al., 2014 |
| Rad21l/RAD21L1 | Unknown | Spermatocytes | 62.7 | 63.3 | 0 | No | Azzospermia, abnormal male meiosis | Yes | Herran et al., 2011 |
| Sox30/SOX30 | TF | Spermatocytes | 83.9 | 82.9 | 0 | No | Abnormal spermatid morphology, arrest of spermiogenesis | Yes | Feng et al., 2017 |
| Spata22/SPATA22 | Unknown | Spermatocytes | 40.2 | 41.3 | 0 | No | Abnormal chromosomal synapsis, abnormal double-strand DNA break repair, abnormal synaptonemal complex | Yes | La Salle et al., 2012 |
| Spdya/SPDYA | Unknown | Spermatocytes | 36.1 | 36.5 | 0 | No | Abnormal chiasmata formation, abnormal chromosomal synapsis, abnormal synaptonemal complex | Yes | Tu et al., 2017 |
| Syce3/SYCE3 | Unknown | Spermatocytes | 10.5 | 10.6 | 0 | No | Abnormal chromosomal synapsis, abnormal synaptonemal complex | Yes | Schramm et al., 2011 |
| Tdrd5/TDRD5 | Epigenetic | Spermatocytes | 116 | 109.7 | 0 | No | Globozoospermia, abnormal acrosome morphology, abnormal spermatocyte morphology, arrest of male meiosis | Yes | Yabuta et al., 2011 |
| Terb1/TERB1 | TF | Spermatocytes | 86.8 | 83.1 | 0 | No | Abnormal X-Y chromosome synapsis during male meiosis | Yes | Shibuya et al., 2014 |
| Topaz1/TOPAZ1 | Unknown | Spermatocytes | 185.5 | 191 | 0 | No | Abnormal male germ cell morphology, arrest of male meiosis | Yes | Luangpraseuth-Prosper et al., 2015 |
| Calr3/CALR3 | Unknown | Spermatids | 42.2 | 42.9 | 0 | Yes | Abnormal sperm physiology | No | Ikawa et al., 2011 |
| Ccdc42/CCDC42 | Unknown | Spermatids | 38 | 38 | 0 | No | Abnormal sperm axoneme morphology, abnormal sperm head morphology, absent sperm flagellum, detached acrosome | No | Pasek et al., 2016 |
| Ccdc62/CCDC62 | Unknown | Spermatids | 79.3 | 77.7 | 0 | No | Abnormal sperm head morphology, abnormal sperm midpiece morphology, abnormal sperm motility, absent acrosome | No | Li et al., 2017 |
| Lrguk/LRGUK | Enzyme | Spermatids | 93.2 | 124.9 | 1 | No | Oligoasthenoteratospermia, manchette dysfunction, abnormal sperm head shaping | Yes | Liu et al., 2015 |
| Prss37/PRSS37 | Enzyme | Spermatids | 24.7 | 24.3 | 0 | Yes | Abnormal sperm physiology, abnormal spermiogenesis, impaired fertilization | Yes | Shen et al., 2013 |
| Rimbp3/RIMBP3B | Unknown | Spermatids | 177.3 | 181 | 0 | No | Detached acrosome, detached sperm flagellum, ectopic manchette | No | Zhou et al., 2009 |
| Spaca1/SPACA1 | Unknown | Spermatids | 30.6 | 29.3 | 1 | Yes | Abnormal acrosome morphology, abnormal sperm head morphology, coiled sperm flagellum | No | Fujihara et al., 2012 |
| Tcte1/TCTE1 | Unknown | Spermatids | 55.5 | 55.6 | 1 | No | Axoneme dysfunction, abnormal sperm motility | No | Castaneda et al., 2017 |
| Tdrd12/TDRD12 | Epigenetic | Spermatids | 137.6 | 132.6 | 0 | No | Abnormal spermatid morphology, arrest of male meiosis | Yes | Asano et al., 2009; Pandey et al., 2013 |
| Atp1a4/ATP1A4 | Transporter | Spermatozoa | 114.9 | 114.2 | 10 | No | Impaired sperm capacitation, kinked sperm flagellum | No | Jimenez et al., 2011 |
| Catsperd/CATSPERD | Unknown | Spermatozoa | 89.5 | 90.4 | 1 | Yes | Abnormal germ cell morphology, reduced hyperactivated sperm motility | No | Chung et al., 2011 |
| Cfap54/CFAP54 | Unknown | Spermatozoa | 353.8 | 352 | 0 | No | Abnormal sperm axoneme morphology, absent sperm flagellum, short sperm flagellum | No | McKenzie et al., 2015 |
| Kcnu1/KCNU1 | IC | Spermatozoa | 126.9 | 129.5 | 7 | No | Impaired acrosome reaction, impaired fertilization, impaired sperm capacitation | No | Santi et al., 2010; Zeng et al., 2011 |
| Pmis2/PMIS2 | Unknown | Spermatozoa | 11 | 15.8 | 2 | No | Abnormal sperm physiology | Unknown | Yamaguchi et al., 2012 |
| Rsph6a/RSPH6A | Unknown | Spermatozoa | 80.2 | 80.9 | 0 | No | Abnormal manchette morphology, abnormal sperm axoneme morphology, abnormal sperm fibrous sheath morphology | No | Abbasi et al., 2018 |
| Sun5/SUN5 | Unknown | Spermatozoa | 42.7 | 43.1 | 2 | No | Globozoospermia, sperm head detachment | No | Shang et al., 2017 |
TM, transmembrane.