# Investigation of how axon development is disrupted by the autism-causing Timothy syndrome mutation.

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN MILWAUKEE · 2022 · $342,000

## Abstract

Autism is a highly heritable neurodevelopmental disorder that has been linked to
variants in many genes. However, the biological basis of autism remains poorly
understood. To gain insight into the mechanisms that cause autism, we are focusing on
the Timothy syndrome mutation, a variant in the CACNA1C voltage gated calcium
channel (VGCC). The Timothy syndrome mutation causes autism with high penetrance,
providing a powerful avenue for investigation of the molecular mechanisms that underlie
autism. Our preliminary data indicate that the Timothy syndrome mutation disrupts axon
targeting in C. elegans, providing a model for understanding the role of VGCC variants
in autism. In aim 1, we will investigate how VGCCs regulate axon targeting and how the
Timothy syndrome mutation alters this process to affect axonal connectivity and
behavior. In aim 2, we will investigate how the Timothy syndrome mutation alters
autophagy and how alterations in this process affect axon targeting. In aim 3, we will
determine if other missense mutations in VGCCs can alter axon targeting. These
studies will provide insight into the biological basis for autism and will identify
interactions between autism-linked genes that could potentially be used to predict and
diagnose autism. Moreover, the CACNA1C gene has also been associated with
schizophrenia, bipolar disorder, major depression and attention deficit hyperactivity
disorder, suggesting that our results are likely to be more broadly applicable to other
neuropsychiatric disorders.

## Key facts

- **NIH application ID:** 10427356
- **Project number:** 5R01MH119157-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN MILWAUKEE
- **Principal Investigator:** CHRISTOPHER C QUINN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $342,000
- **Award type:** 5
- **Project period:** 2019-09-24 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427356

## Citation

> US National Institutes of Health, RePORTER application 10427356, Investigation of how axon development is disrupted by the autism-causing Timothy syndrome mutation. (5R01MH119157-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10427356. Licensed CC0.

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