---
title: "CAMSAP3 loss-of-function evidence implicates gene in generalized genetic epilepsy"
id: "biorxiv-1-camsap3-loss-of-function-models-suggest-causative-role-in-generalized-genetic"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-1-camsap3-loss-of-function-models-suggest-causative-role-in-generalized-genetic"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.01.744686v1?rss=1"
published_at: "2026-09-04T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# CAMSAP3 loss-of-function evidence implicates gene in generalized genetic epilepsy
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-1-camsap3-loss-of-function-models-suggest-causative-role-in-generalized-genetic
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.01.744686v1?rss=1)
- **Published At:** 2026-09-04T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Next-generation sequencing revealed predicted pathogenic CAMSAP3 variants in two patients with **generalized epilepsy**, prompting functional follow-up. - CAMSAP3 encodes a regulator of non-centrosomal microtubule dynamics important for axonal differentiation and migration. - Overexpression of patient-derived CAMSAP3 variants in cultured HEK cells caused **protein degradation** and altered **microtubule acetylation**, indicating disrupted protein stability and cytoskeletal regulation. - A Camsap3 knockout zebrafish model showed elevated axonal **microtubule acetylation**, paralleling the cell-culture phenotype and supporting a loss-of-function mechanism. - Knockout zebrafish displayed behavioral and electrophysiologic hallmarks of epilepsy: seizure-like swimming behaviors and **epileptiform** activity recorded by local field potential. - Development of inhibitory interneurons was abnormal in Camsap3 knockout zebrafish, suggesting a developmental mechanism that could contribute to network hyperexcitability. - The convergence of human genetic data, cellular assays, and an animal knockout model supports a causative role for **CAMSAP3** in at least some forms of generalized genetic epilepsy. - The authors declare no competing interests and acknowledge funding from the National Institute of Neurological Disorders and Stroke and other listed sources. - These results provide functional validation for CAMSAP3 as an epilepsy-associated gene but further clinical and mechanistic studies were not reported in the source and remain necessary to inform patient management.
## Clinical Analysis & Structured Key Points
CAMSAP3 loss of function models suggest causative role in generalized genetic epilepsy | bioRxiv Skip to main content New Results CAMSAP3 loss of function models suggest causative role in generalized genetic epilepsy View ORCID Profile Christopher Mark LaCoursiere , View ORCID Profile Zachary Stayn , View ORCID Profile Hannah Hepner , View ORCID Profile Sneham Tiwari , View ORCID Profile Joseph Pascucci , Chariton Moschopoulos , View ORCID Profile Lacey Smith , Hyun Yong Koh , View ORCID Profile Parul Chaudhary , View ORCID Profile Annapurna Poduri doi: https://doi.org/10.64898/2026.09.01.744686 Christopher Mark LaCoursiere 1 Boston Childrens Hospital; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Christopher Mark LaCoursiere Zachary Stayn 2 Harvard University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Zachary Stayn Hannah Hepner 2 Harvard University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Hannah Hepner Sneham Tiwari 3 Boston Children's Hospital; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sneham Tiwari Joseph Pascucci 3 Boston Children's Hospital; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Joseph Pascucci Chariton Moschopoulos 3 Boston Children's Hospital; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Lacey Smith 3 Boston Children's Hospital; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Lacey Smith Hyun Yong Koh 4 Baylor College of Medicine Find this author on Google Scholar Find this author on PubMed Search for this author on this site Parul Chaudhary 3 Boston Children's Hospital; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Parul Chaudhary Annapurna Poduri 3 Boston Children's Hospital; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Annapurna Poduri For correspondence: annapurna.poduri{at}childrens.harvard.edu Abstract Info/History Metrics Supplementary material Preview PDF Abstract Advancements in next generation sequencing have led to the discovery of hundreds of human epilepsy gene associations. Newly associated genes require functional validation to establish causation and to inform patient treatment in the clinic. A recent exome trio analysis identified predicted pathogenic variants in two patients with generalized epilepsy in the gene CAMSAP3. CAMSAP3 regulates non-centrosomal microtubule dynamics, and the acetylation necessary for normal axonal differentiation and migration. We show that overexpression of patient variants leads to protein degradation and dysregulation of microtubule acetylation in cultured HEK cells. Camsap3 knockout zebrafish also exhibit increased axonal microtubule acetylation as well as epileptic features such as seizure-like swimming behaviors, aberrant inhibitory interneuron development and epileptiform via local field potential. Together these data suggest that CAMSAP3 plays an important role in generalized genetic epilepsy. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared National Institute of Neurological Disorders and Stroke, https://ror.org/01s5ya894 Rosamund Stone Zander Hansjoerg Wyss Translational Neuroscience Center Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Back to top Previous Next Posted September 04, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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Share CAMSAP3 loss of function models suggest causative role in generalized genetic epilepsy Christopher Mark LaCoursiere , Zachary Stayn , Hannah Hepner , Sneham Tiwari , Joseph Pascucci , Chariton Moschopoulos , Lacey Smith , Hyun Yong Koh , Parul Chaudhary , Annapurna Poduri bioRxiv 2026.09.01.744686; doi: https://doi.org/10.64898/2026.09.01.744686 Share This Article: Copy Citation Tools CAMSAP3 loss of function models suggest causative role in generalized genetic epilepsy Christopher Mark LaCoursiere , Zachary Stayn , Hannah Hepner , Sneham Tiwari , Joseph Pascucci , Chariton Moschopoulos , Lacey Smith , Hyun Yong Koh , Parul Chaudhary , Annapurna Poduri bioRxiv 2026.09.01.744686; doi: https://doi.org/10.64898/2026.09.01.744686 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (7960) Biochemistry (18613) Bioengineering (14759) Bioinformatics (44099) Biophysics (22438) Cancer Biology (19579) Cell Biology (26725) Clinical Trials (138) Developmental Biology (13894) Ecology (20869) Epidemiology (2067) Evolutionary Biology (25287) Genetics (16091) Genomics (23374) Immunology (18582) Microbiology (42208) Molecular Biology (17936) Neuroscience (92791) Paleontology (693) Pathology (2967) Pharmacology and Toxicology (5059) Physiology (8049) Plant Biology (15897) Scientific Communication and Education (2091) Synthetic Biology (4536) Systems Biology (10180) Zoology (2375)
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