# Elucidating the synaptic interactome of the high risk autism gene ANK2

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $448,484

## Abstract

PROJECT SUMMARY
Network gene analysis suggests that high confidence autism spectrum disorder (hcASD) genes operate through
convergent mechanisms that predominantly support synaptic function, which, in turn, can determine anatomical
and functional brain connectivity. Several variants in ANK2 have been identified in ASD patients and this gene
has been consistently considered a top hcASD risk. ANK2 encodes ankyrin-B (AnkB), which roles in axonal
biology may be an underlying factor in ASD pathophysiology. However, our recent findings indicate that ankyrin-
B also plays important roles at the cortical excitatory postsynapse. Moreover, both predominant AnkB isoforms
in neurons (220 kDa and 440 kDa AnkB) are abundantly expressed in dendrites, where they likely perform
isoform-specific roles and interact with unique partners, including proteins encoded by other hsASD genes. Thus,
it is important to define the isoform-specific roles and partners of AnkB at the postsynapse. To accomplish these
goal we will 1) use in vivo proximity-dependent biotin identification (iBioID) combined with in tandem mass
spectrometry (MS) to capture and identify AnkB interacting partners in the postsynapse by leveraging our novel
biotin ligase BirA-tagged conditional AnkB (AnkB-BioID) knock-in mouse and isoform-specific AnkB knockout
mice; 2) combine live and super-resolution microscopies and cellular assays to validate compelling AnkB
interactors; and 3) define the significance of novel AnkB PSD complexes for synaptic development and function.

## Key facts

- **NIH application ID:** 10745355
- **Project number:** 5R01MH127848-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Damaris N Lorenzo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $448,484
- **Award type:** 5
- **Project period:** 2022-12-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10745355

## Citation

> US National Institutes of Health, RePORTER application 10745355, Elucidating the synaptic interactome of the high risk autism gene ANK2 (5R01MH127848-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10745355. Licensed CC0.

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