# Mechanisms of ciliopathy associated structural birth defects > **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $602,956 ## Abstract PROJECT SUMMARY/ABSTRACT Cilia are complex structures with more than 1,300 proteins involved in their formation and function. During development, disruption of cilia function causes gestational lethality and mild to severe birth defects. Variants in cilia proteins are causally associated with more than 35 ciliopathy syndromes. Ciliopathy patients have a wide range of phenotypes affecting nearly every organ system. Despite the cilium's clinical importance, the functions of the cilium and molecular pathways the cilium regulates are poorly defined. To understand the pathophysiological mechanisms driving ciliopathy birth defects, we are extending and utilizing protocols, expertise, and tools developed within the UAB U54 Center for Precision Animal Modeling (CPAM). We will identify and characterize variants of interest derived from patient and variant repositories from local, regional, and national/international sources. Both variants of unknown significance (VUS) in known ciliopathy genes and predicted deleterious variants of interest identified in novel candidate ciliopathy genes that we prioritize through this application will be selected. Each variant will undergo robust assessment based on known or predicted deleteriousness, pathway and protein interactions, and phenotype and functional associations as compared to known ciliopathies. Prioritized variants will be subjected to a robust wet lab process to test pathogenicity, determine ciliopathy protein cellular localization, and screen rapidly for cilia related phenotypes in zebrafish F0 Crispant mutants. For variants that remain highly prioritized after these steps, we will generate precision engineered mouse models corresponding to the patient variant. These models will undergo phenotype analyses to assess the clinical correlation between the model and the patient. We will analyze the variant's impact on cilia assembly, morphology, formation of specialized cilia sub-compartments, and disruption of cilia protein interaction networks. We will determine the impact of the variant on developmental signaling pathways known to be associated with the cilium as well as identify novel pathways not previously identified as being regulated by the cilium. To accomplish the goals of project, we have assembled a team with a wide range of expertise in medicine, genetics and molecular diagnostics, computational biology, bioinformatics, and data science, biochemistry, cell biology, and animal model generation and phenotyping. Collectively we will confirm the functional impact of variants identified in patients with ciliopathy-like birth defects and patients with variants in genes predicted but not already well known to affect the cilium or its activity. The outcomes from this project will uncover novel cilia protein interactions and subcomplexes involved in cilia formation and maintenance, cilia protein transport, and cilia sensory and signaling activities. This work will also support definitive diagnoses for pati... ## Key facts - **NIH application ID:** 10794534 - **Project number:** 1R01HD111399-01A1 - **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM - **Principal Investigator:** Bradley K. Yoder - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $602,956 - **Award type:** 1 - **Project period:** 2024-09-06 → 2029-07-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10794534 ## Citation > US National Institutes of Health, RePORTER application 10794534, Mechanisms of ciliopathy associated structural birth defects (1R01HD111399-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10794534. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*