ArticleHuman genetics2021
A missense mutation in IFT74, encoding for an essential component for intraflagellar transport of Tubulin, causes asthenozoospermia and male infertility without clinical signs of Bardet-Biedl syndrome.
Article in Human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- The genetic insights of sporadic male infertility: a systematic review of WES and WGS studies (2014-2024).Human genomics · 2026Pooled it
- Human asthenozoospermia: Update on genetic causes, patient management, and clinical strategies.Andrology · 2025Review
- Defective IFT57 underlies a novel cause of Bardet-Biedl syndrome.Human molecular genetics · 2025Article
- Intraflagellar Transport (IFT) and Sperm Formation.Advances in experimental medicine and biology · 2025Review
- Review
- Structure and Composition of Spermatozoa Fibrous Sheath in Diverse Groups of Metazoa.International journal of molecular sciences · 2024Review
- Review
- Article
- Effects ofHuman reproduction open · 2024Article
- CCDC146 is required for sperm flagellum biogenesis and male fertility in mice.Cellular and molecular life sciences : CMLS · 2023Article
- Defective airway intraflagellar transport underlies a combined motile and primary ciliopathy syndrome caused by IFT74 mutations.Human molecular genetics · 2023Article
- IFT74 variants cause skeletal ciliopathy and motile cilia defects in mice and humans.PLoS genetics · 2023Article
- Loss-of-function mutations in CFAP57 cause multiple morphological abnormalities of the flagella in humans and mice.JCI insight · 2023Article
- New Mutations in DNHD1 Cause Multiple Morphological Abnormalities of the Sperm Flagella.International journal of molecular sciences · 2023Article
- Clinical detection, diagnosis and treatment of morphological abnormalities of sperm flagella: A review of literature.Frontiers in genetics · 2022Review
- Identification of bi-allelicFrontiers in endocrinology · 2022Article
- Bi-allelic truncating variants in CFAP206 cause male infertility in human and mouse.Human genetics · 2021Article
- Loss of Ift74 Leads to Slow Photoreceptor Degeneration and Ciliogenesis Defects in Zebrafish.International journal of molecular sciences · 2021Article
- Biallelic Variants inFrontiers in cell and developmental biology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
Abstract
Cilia and flagella are formed around an evolutionary conserved microtubule-based axoneme and are required for fluid and mucus clearance, tissue homeostasis, cell differentiation and movement. The formation and maintenance of cilia and flagella require bidirectional transit of proteins along the axonemal microtubules, a process called intraflagellar transport (IFT). In humans, IFT defects contribute to a large group of systemic diseases, called ciliopathies, which often display overlapping phenotypes. By performing exome sequencing of a cohort of 167 non-syndromic infertile men displaying multiple morphological abnormalities of the sperm flagellum (MMAF) we identified two unrelated patients carrying a homozygous missense variant adjacent to a splice donor consensus site of IFT74 (c.256G > A;p.Gly86Ser). IFT74 encodes for a core component of the IFT machinery that is essential for the anterograde transport of tubulin. We demonstrate that this missense variant affects IFT74 mRNA splicing and induces the production of at least two distinct mutant proteins with abnormal subcellular localization along the sperm flagellum. Importantly, while IFT74 deficiency was previously implicated in two cases of Bardet-Biedl syndrome, a pleiotropic ciliopathy with variable expressivity, our data indicate that this missense mutation only results in primary male infertility due to MMAF, with no other clinical features. Taken together, our data indicate that the nature of the mutation adds a level of complexity to the clinical manifestations of ciliary dysfunction, thus contributing to the expanding phenotypical spectrum of ciliopathies.
Indexed as
Identifiers
What OpenQuestion holds
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.