# The Discovery of Human Peptide Encoding Genes

> **NIH NIH R01** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2023 · $483,123

## Abstract

ABSTRACT
 Understanding the information contained within the human genome has been a goal of molecular biology
and medicine since the identification of DNA. The Human Genome Project cataloged all the protein-coding genes
embedded within the genome, but gene-finding algorithms had a blind spot for protein-coding small open reading
frames (smORFs). Technological advances over the last decade have led to the discovery of thousands of
smORFs in the human genome that encode peptides or small proteins (median length 30 amino acids)
collectively referred to as microproteins. The discovery of thousands of previously unknown proteins in the
human genome is an exciting opportunity in molecular biology that promises to improve scientific understanding
and the ability to discover and develop new medicines.
 This proposal seeks to answer important questions that have emerged regarding microproteins, including
whether microproteins from polycistronic genes are functional (Aim 1), whether biologically active secreted
microproteins exist (Aim 2), and, lastly, whether it is possible to use knowledge about the structure and
mechanism of microproteins to develop small-molecule probes that can regulate their actives in cells (Aim 3).
These questions will be tackled using approaches and reagents developed over the last decade. For example,
optimized robust protocols are now available for investigating microprotein-protein interactions together with
necessary reagents including antibodies, cell lines, and genetically engineered mice to study these unique
genes. This proposal will reveal new functions for microproteins in cells and tissues, identify biologically active
secreted microproteins, and identify small molecule probes of microprotein biology.
 These efforts will increase understanding of the roles of smORFs and microproteins in mammalian
genomes and identify secreted microproteins and small molecules that provide a template for converting these
foundational discoveries into medicines.

## Key facts

- **NIH application ID:** 10695089
- **Project number:** 5R01GM102491-11
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Clodagh O'Shea
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $483,123
- **Award type:** 5
- **Project period:** 2012-09-21 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10695089

## Citation

> US National Institutes of Health, RePORTER application 10695089, The Discovery of Human Peptide Encoding Genes (5R01GM102491-11). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10695089. Licensed CC0.

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