Work

Integrative modelling and in vivo analysis identify hypomorphic TMEM17 ciliopathy variants that reduce transition-zone abundance of TMEM-17

Year: 2026

Type: software

Abstract: The study integrates computational pathogenicity prediction, structural modelling, and in vivo functional assays in Caenorhabditis elegans to evaluate the impact of clinically reported TMEM17 missense variants. A consensus multi-predictor framework, supported by evolutionary conservation and AlphaFold-based structural modelling, prioritizes deleterious substitutions and predicts disruption of transition-zone interaction interfaces. Functional validation using CRISPR-engineered endogenous tmem-17 alleles demonstrates that p.Gly101Val and p.Pro123Arg act as hypomorphic variants, reducing TMEM-17 abundance at the ciliary transition zone without affecting basal body localization. Phenotypic consequences are minimal in a wild-type background but become pronounced in a sensitized nphp-4 mutant context, revealing ciliary defects consistent with partial loss of function.

Source: Zenodo (CERN European Organization for Nuclear Research)

DOI: 10.5281/zenodo.20391326

Authors: YENİSERT, FERHAN, AlAbdi, Lama, Cevik, Sebiha, Alkuraya, Fowzan, Kaplan, Oktay Ismail

Institutions: Abdullah Gül University, King Faisal Specialist Hospital & Research Centre, Alfaisal University

Language: English

Topic: Genetic and Kidney Cyst Diseases

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W7165193825

Cites:

Cited by:

Related to: 10