Table 1.
Overview of disease-associated X-linked genes with testis-specific expression in mice and humans
| Gene | Semen/testicular phenotype | Proposed functions | Mouse phenotype | Publications | Level of evidence |
|---|---|---|---|---|---|
| Phenotype: isolated spermatogenic failure | |||||
| AR | Oligozoospermia, azoospermia | Hormone activated transcription factor | Infertile; partial androgen insensitivity syndrome | Hiort et al. (2000), Ferlin et al. (2006) | Definitive |
| TEX11 | Non-obstructive azoospermia, meiotic arrest | Meiotic DNA recombination | Infertile; meiotic arrest | Yang et al. (2015a), Yatsenko et al. (2015) | Strong |
| MAGEB4 | Non-obstructive azoospermia | Germ cell-specific mitosis | No mouse model | Okutman et al. (2017) | Limited |
| HAUS7 | Severe oligozoospermia | Meiotic chromosome alignment | No mouse model | Li et al. (2018) | Limited |
| USP26 | Oligozoospermia, azoospermia | Deubiquitinating peptidase | Fertile | Paduch et al. (2005) | Limited |
| RHOXF1/2 | Oligozoospermia, severe | Homeodomain transcription factor | No mouse model | Borgmann et al. (2016) | No evidence |
| TAF7L | Non-obstructive azoospermia | TFIID transcription factor | Complete spermatogenesis; abnormal sperm number/morphology | Akinloye et al. (2007) | No evidence |
| Phenotype: obstructive azoospermia/CBAVD | |||||
| ADGRG2 | Congenital bilateral absence of the vas deferens (CBAVD) | G-protein-dependent fluid homeostasis | Infertile; obstructive | Patat et al. (2016) | Strong |
| CLDN2 | Obstructive azoospermia | BTB tight junction formation | Fertile | Askari et al. (2019) | Limiteda |
| Phenotype: astheno-/teratozoospermia | |||||
| PIH1D3 | Asthenozoospermia | Flagella dynein assembly | Infertile; mild PCD | Paff et al. (2017), Olcese et al. (2017) | Strong |
| AKAP4 | Asthenozoospermia, teratozoospermia | PKA binding in sperm flagellum | Infertile; multiple morphological abnormalities of the sperm flagella | Baccetti et al. (2005), Visser et al. (2011) | Limited |
| FATE1 | Oligoasthenozoospermia | SF1-dependent mitochondrial regulation | No mouse model | Olesen et al. (2003) | No evidence |
| Phenotype: Kallmann syndrome | |||||
| ANOS1 | Oligozoospermia, azoospermia | GnRH neuronal migration | Infertile; hypogonadotropic hypogonadism | Gonçalves et al. (2017) | Definitive |
aNot in Oud et al. (2019) because published subsequently. Assessment according to same criteria by MV and FT independently