Wednesday, December 31, 2025 12/31/2025

Convergent mechanisms for neurodevelopmental disorder genes

Award Number: R01MH126960
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/14/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2026

Group Awards By:

View Award Description

Convergent mechanisms for neurodevelopmental disorder genes - Convergent Mechanisms for Neurodevelopmental Disorder Genes Voltage-gated sodium channels (NaVs) are essential regulators of neuronal excitability, making the dysfunction of NaVs a serious public health concern. Genetic variants in SCN2A and SCN8A, which encode the neuronal sodium channels NaV1.2 and NaV1.6, respectively, have been identified in several human patient cohorts of neurodevelopmental disorders, including autism spectrum disorder (ASD) and epileptic encephalopathy (EE). The proper localization of NaVs is dependent on their interactions with ankyrins, a family of intracellular scaffolding proteins that link essential membrane-bound proteins to the underlying cytoskeleton. Our lab and others have established ankyrin-G, encoded by ANK3, as the master organizer of the axon initial segment (AIS), a key site of neuronal excitability. Ankyrin-G scaffolds proteins to the AIS, including NaV1.2 and NaV1.6. Our lab recently identified a critical interaction between NaV1.2 and ankyrin-B, encoded by ANK2, in mature neocortical pyramidal cell dendrites, where NaV1.2 regulates dendritic excitability. Previous studies have identified the key residues required for the binding of ankyrins and NaVs. The key residues required for the interaction between ankyrin-B and NaV1.2 are found within the ankyrin-repeats of ankyrin-B and the intracellular loop between domains II and III (II-III loop) of NaV1.2. These residues are conserved among ankyrin-B and ankyrin-G, and NaV1.2 and NaV1.6. Despite this conservation, ankyrins and NaVs have distinct neuronal localization, suggesting that regions outside of the required residues play a role in the coordination of NaVs. However, it remains unknown which amino acid sequences determine binding affinity between ankyrins and NaVs to mediate differential ankyrin-dependent coordination of NaVs. Our preliminary data indicate that mutations near the ankyrin/NaV binding interface affect the binding affinity between ankyrin-B and NaV1.2. The effects of these mutations on the binding affinity between NaV1.2 and ankyrin-G, however, have not been characterized. Furthermore, potential interactions between ankyrin-B and NaV1.6 have not been studied. Altered binding affinities could explain differences in the localization and function of these proteins. In addition, limitations in immunocytochemistry techniques have prevented a close study of NaV1.6 localization outside the AIS. These results would provide critical information regarding the ankyrin-dependent coordination of NaVs and ultimately help us determine how dysfunction of ankyrins and NaVs contribute to the etiology underlying neurodevelopmental disorders.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Mental Health Research Grants	001	5	11/20/2025	NON-COMPETING CONTINUATION	$0
2026	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Mental Health Research Grants	000	4	11/20/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $519,495 )
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Mental Health Research Grants	003	5	9/24/2025	NON-COMPETING CONTINUATION	$77,925
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Mental Health Research Grants	000	5	3/29/2025	NON-COMPETING CONTINUATION	$441,570
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Mental Health Research Grants	001	5	4/25/2025	NON-COMPETING CONTINUATION	$0
2025	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Mental Health Research Grants	002	4	4/28/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $519,495

Issue Date FY: 2024 ( Subtotal = $605,524 )
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Mental Health Research Grants	002	4	8/14/2024	NON-COMPETING CONTINUATION	$51,950
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Mental Health Research Grants	001	4	3/1/2024	SUPPLEMENT FOR EXPANSION	$86,029
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Mental Health Research Grants	000	4	2/7/2024	NON-COMPETING CONTINUATION	$467,545
														Subtotal = $605,524

Issue Date FY: 2023 ( Subtotal = $467,546 )
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Mental Health Research Grants	000	3	1/31/2023	NON-COMPETING CONTINUATION	$467,546
														Subtotal = $467,546

Issue Date FY: 2022 ( Subtotal = $515,750 )
2022	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Mental Health Research Grants	001	2	6/21/2022	NON-COMPETING CONTINUATION	$51,574
2022	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Mental Health Research Grants	000	2	2/9/2022	NON-COMPETING CONTINUATION	$464,176
														Subtotal = $515,750

Issue Date FY: 2021 ( Subtotal = $556,895 )
2021	2021	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Mental Health Research Grants	000	1	5/13/2021	NEW	$556,895
														Subtotal = $556,895

Grand Total All Awards = $2,665,210

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Convergent mechanisms for neurodevelopmental disorder genes

Award Number: R01MH126960

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/14/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer