ArticleHuman molecular genetics2016
The human RHOX gene cluster: target genes and functional analysis of gene variants in infertile men.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- A systematic review and standardized clinical validity assessment of male infertility genes.Human reproduction (Oxford, England) · 2019Pooled it
- Pervasive Positive Selection on X-linked Ampliconic Genes in Primates.Genome biology and evolution · 2026Article
- RHOX Homeobox Transcription Factor Regulation ofCells · 2025Article
- Sperm epigenetics and male infertility: unraveling the molecular puzzle.Human genomics · 2024Review
- Mammal Reproductive Homeobox (Rhox) Genes: An Update of Their Involvement in Reproduction and Development.Genes · 2023Review
- Unravelling transmission ratio distortion across the bovine genome: identification of candidate regions for reproduction defects.BMC genomics · 2023Article
- Acquisition of Immune Privilege in GBM Tumors: Role of Prostaglandins and Bile Salts.International journal of molecular sciences · 2023Article
- Genome-Wide Association Screening Determines Peripheral Players in Male Fertility Maintenance.International journal of molecular sciences · 2022Article
- Identification of Genetic Effects ofGenes · 2022Article
- Computational detection of a genome instability-derived lncRNA signature for predicting the clinical outcome of lung adenocarcinoma.Cancer medicine · 2022Article
- TheProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Impact of aging on gene expression response to x-ray irradiation using mouse blood.Scientific reports · 2021Article
- Single-cell analysis of the developing human testis reveals somatic niche cell specification and fetal germline stem cell establishment.Cell stem cell · 2021Article
- The X chromosome and male infertility.Human genetics · 2021Review
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- Article
- High-resolution analysis of germ cells from men with sex chromosomal aneuploidies reveals normal transcriptome but impaired imprinting.Clinical epigenetics · 2019Article
- Ran-binding protein M is associated with human spermatogenesis and oogenesis.Molecular medicine reports · 2018Article
- Genetic effects of PDGFRB and MARCH1 identified in GWAS revealing strong associations with semen production traits in Chinese Holstein bulls.BMC genetics · 2017Article
- A no-stop mutation in MAGEB4 is a possible cause of rare X-linked azoospermia and oligozoospermia in a consanguineous Turkish family.Journal of assisted reproduction and genetics · 2017Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The X-linked reproductive homeobox (RHOX) gene cluster encodes transcription factors preferentially expressed in reproductive tissues. This gene cluster has important roles in male fertility based on phenotypic defects of Rhox-mutant mice and the finding that aberrant RHOX promoter methylation is strongly associated with abnormal human sperm parameters. However, little is known about the molecular mechanism of RHOX function in humans. Using gene expression profiling, we identified genes regulated by members of the human RHOX gene cluster. Some genes were uniquely regulated by RHOXF1 or RHOXF2/2B, while others were regulated by both of these transcription factors. Several of these regulated genes encode proteins involved in processes relevant to spermatogenesis; e.g. stress protection and cell survival. One of the target genes of RHOXF2/2B is RHOXF1, suggesting cross-regulation to enhance transcriptional responses. The potential role of RHOX in human infertility was addressed by sequencing all RHOX exons in a group of 250 patients with severe oligozoospermia. This revealed two mutations in RHOXF1 (c.515G > A and c.522C > T) and four in RHOXF2/2B (-73C > G, c.202G > A, c.411C > T and c.679G > A), of which only one (c.202G > A) was found in a control group of men with normal sperm concentration. Functional analysis demonstrated that c.202G > A and c.679G > A significantly impaired the ability of RHOXF2/2B to regulate downstream genes. Molecular modelling suggested that these mutations alter RHOXF2/F2B protein conformation. By combining clinical data with in vitro functional analysis, we demonstrate how the X-linked RHOX gene cluster may function in normal human spermatogenesis and we provide evidence that it is impaired in human male fertility.
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