Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Pilot Studies on SCYL2, an AMC-Associated Protein, in Endocytosis and Neuronal Development

Award Number: R03TR006462
ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2027

Group Awards By:

View Award Description

Pilot Studies on SCYL2, an AMC-Associated Protein, in Endocytosis and Neuronal Development - Project Summary/Abstract Many rare diseases result from single-gene mutations. Studying these disease-associated genes is crucial, as investigating their genotype-phenotype relationships can reveal the physiological roles of key cellular pathways relevant to both rare and common diseases. Because mutations in different genes within the same cellular pathways can produce similar pathological mechanisms, systematically investigating disease-associated genes within shared pathways and developing broadly applicable approaches to study them can greatly advance understanding of key cellular pathways and disease mechanisms. Responding to the funding opportunity for Pilot Projects Investigating Understudied Proteins Associated with Rare Diseases, this project aims to test the hypothesis that the understudied protein SCYL2 participates in clathrin-mediated endocytosis (CME) and that its loss of function disrupts endocytosis and neuronal differentiation, contributing to Arthrogryposis Multiplex Congenita type 4 (AMC4) pathology. This project serves as a starting point for a long-term objective: establishing a systematic framework for investigating the dynamics and functions of disease-associated endocytic proteins during development. AMC4 is a rare developmental disorder caused by loss-of-function variants in SCYL2, a putative kinase implicated in clathrin-mediated vesicle trafficking. AMC4 is characterized by multiple joint contractures and other neurogenic phenotypes, including brain malformations, agenesis of the corpus callosum, hypotonia, and epilepsy. Although SCYL2 interacts with coat proteins such as clathrin and AP2 adaptors, its role in CME remains unclear, partly due to limitations in approaches used to study endocytosis in prior decades. Understanding SCYL2’s function in endocytosis and neuronal development is essential for elucidating the cellular and molecular mechanisms underlying both CME and AMC4. Using human induced pluripotent stem cells (hiPSCs), genome editing, advanced live-cell imaging, and computational analysis, this study will apply newly developed quantitative pipelines that enable high-throughput analysis of endocytic protein dynamics as well as sensitive detection of CME defects through the following aims: Aim 1: Determine whether endogenous SCYL2 is recruited to endocytic sites. Aim 2: Test whether AMC4-associated SCYL2 variants affect endocytosis. Aim 3: Assess whether AMC4-associated SCYL2 variants impact neuronal endocytosis and differentiation. This project will generate genome-edited hiPSC lines as essential research tools and produce preliminary data elucidating the molecular mechanisms of SCYL2 in CME and neuronal development. The findings will advance understanding of CME regulation and AMC4 pathogenesis and establish broadly applicable methods for studying other disease-associated endocytic proteins in future research.


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 = $153,500 )
2026	2026	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	National Center for Advancing Translational Sciences	000	1	7/7/2026	NEW	$153,500
														Subtotal = $153,500

Grand Total All Awards = $153,500

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Pilot Studies on SCYL2, an AMC-Associated Protein, in Endocytosis and Neuronal Development

Award Number: R03TR006462

ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer