ArticlePLoS genetics2014
A nonsense mutation in TMEM95 encoding a nondescript transmembrane protein causes idiopathic male subfertility in cattle.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 4 of them syntheses that pooled it.
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Who cites it
49 citing papers in PubMed, 4 syntheses or guidelines pooled it, 112 citations in OpenAlex.
- The Role of Sperm Proteins IZUMO1 and TMEM95 in Mammalian Fertilization: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Genetic mechanisms underlying spermatic and testicular traits within and among cattle breeds: systematic review and prioritization of GWAS results.Journal of animal science · 2018Pooled it
- Meta-analysis of sequence-based association studies across three cattle breeds reveals 25 QTL for fat and protein percentages in milk at nucleotide resolution.BMC genomics · 2017Pooled it
- A multi-trait meta-analysis with imputed sequence variants reveals twelve QTL for mammary gland morphology in Fleckvieh cattle.Genetics, selection, evolution : GSE · 2016Pooled it
- Molecular interplay between sperm and oocyte: a narrative review.Human reproduction update · 2026Review
- Structure and inhibition of the sperm TMEM95-FIMP complex in mammalian fertilization.bioRxiv : the preprint server for biology · 2026Article
- The SPARK complex forms the molecular basis of vertebrate fertilization.bioRxiv : the preprint server for biology · 2026Article
- Membrane Fusions During Mammalian Fertilization.Advances in experimental medicine and biology · 2026Review
- Developmental origins of pregnancy loss in cattle.Animal reproduction · 2026Article
- The role of ladderlectin in spermatogenesis and ovarian sperm storage in the black rockfish (Sebastes schlegelii).Communications biology · 2025Article
- Allosteric inhibition of the IZUMO1-JUNO fertilization complex by the naturally occurring antisperm antibody OBF13.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Decoding the Genes Orchestrating Egg and Sperm Fusion Reactions and Their Roles in Fertility.Biomedicines · 2024Review
- The effects of case/control ratio and sample size on genome-wide association studies: A simulation study.Veterinary medicine and science · 2024Article
- Molecular quantitative trait loci in reproductive tissues impact male fertility in cattle.Nature communications · 2024Article
- Adenylate kinase 9 is essential for sperm function and male fertility in mammals.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A Frame-by-Frame Glance at Membrane Fusion Mechanisms: From Viral Infections to Fertilization.Biomolecules · 2023Review
- Analysis of amplification and association polymorphisms in the bovine beta-defensin 129 (BBD129) gene revealed its function in bull fertility.Scientific reports · 2022Article
- Human sperm TMEM95 binds eggs and facilitates membrane fusion.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Genetic Diversity and Selective Signature in Dabieshan Cattle Revealed by Whole-Genome Resequencing.Biology · 2022Article
- Testis-Specific Isoform of NaInternational journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic variants underlying reduced male reproductive performance have been identified in humans and model organisms, most of them compromising semen quality. Occasionally, male fertility is severely compromised although semen analysis remains without any apparent pathological findings (i.e., idiopathic subfertility). Artificial insemination (AI) in most cattle populations requires close examination of all ejaculates before insemination. Although anomalous ejaculates are rejected, insemination success varies considerably among AI bulls. In an attempt to identify genetic causes of such variation, we undertook a genome-wide association study (GWAS). Imputed genotypes of 652,856 SNPs were available for 7962 AI bulls of the Fleckvieh (FV) population. Male reproductive ability (MRA) was assessed based on 15.3 million artificial inseminations. The GWAS uncovered a strong association signal on bovine chromosome 19 (P = 4.08 × 10(-59)). Subsequent autozygosity mapping revealed a common 1386 kb segment of extended homozygosity in 40 bulls with exceptionally poor reproductive performance. Only 1.7% of 35,671 inseminations with semen samples of those bulls were successful. None of the bulls with normal reproductive performance was homozygous, indicating recessive inheritance. Exploiting whole-genome re-sequencing data of 43 animals revealed a candidate causal nonsense mutation (rs378652941, c.483C>A, p.Cys161X) in the transmembrane protein 95 encoding gene TMEM95 which was subsequently validated in 1990 AI bulls. Immunohistochemical investigations evidenced that TMEM95 is located at the surface of spermatozoa of fertile animals whereas it is absent in spermatozoa of subfertile animals. These findings imply that integrity of TMEM95 is required for an undisturbed fertilisation. Our results demonstrate that deficiency of TMEM95 severely compromises male reproductive performance in cattle and reveal for the first time a phenotypic effect associated with genomic variation in TMEM95.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.