# Role of CHAMP1, a neurodevelopmental disorder high risk gene, in human brain development and function

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $556,895

## Abstract

PROJECT SUMMARY
Nonsense or missense mutations of the CHAMP1 gene, which encodes for a zinc-finger protein involved in the
maintenance of kinetochore-microtubule attachment during mitosis and regulation of chromosomal segregation,
causes a neurodevelopmental syndrome characterized by intellectual disability (ID), ASD-like behaviors,
microcephaly, hypotonia, and dysmorphic features. CHAMP1 interacts with POGZ, which encodes for a gene
that causes the White-Sutton syndrome, and it is known that the interaction of these two proteins is lost in the
presence of mutations. To date, 36 disease rare variants in CHAMP1 have been reported across studies
comprising nonsense, missense, and frameshift mutations. Recently, a Champ1+/- mouse model showed
relatively mild learning and memory impairment and depression-like behaviors and delayed neuronal
differentiation. Despite the mouse data, there is yet no study that focused on the human brain leaving the role of
CHAMP1 in human brain development totally unexplored.
As such, our central hypothesis is that CHAMP1 loss of function alter neurogenesis and neuronal migration in
human brain resulting in dysfunction of cortical local circuits.
We propose a series of complementary approaches, including high-resolution imaging, single-cell multiomics,
and electrophysiology tools to explore CHAMP1 loss of function in the following specific aims:
Specific Aim 1. Determine the influence of CHAMP1 loss of function in the development of forebrain cortical
organoids.
Specific Aim 2. Profile single cell level transcriptomic and epigenomic landscapes of CHAMP1 loss of function
organoids at different developmental stages.
Specific Aim 3. Determine the effect of CHAMP1 loss of function in neuronal activity and local network.

## Key facts

- **NIH application ID:** 10936363
- **Project number:** 1R01HD113594-01A1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Stefano Berto
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $556,895
- **Award type:** 1
- **Project period:** 2024-09-19 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10936363

## Citation

> US National Institutes of Health, RePORTER application 10936363, Role of CHAMP1, a neurodevelopmental disorder high risk gene, in human brain development and function (1R01HD113594-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10936363. Licensed CC0.

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