# Probing genetics and biology of human sleep homeostasis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $666,175

## Abstract

Project Summary
Familial Natural Short Sleep (FNSS) is a rare Mendelian form of sleep where affected individuals have a lifelong
requirement for sleep that is significantly less than the average person. These people often sleep 4-6 hours per
night yet report feeling well-rested. In 2009, we reported the first human FNSS trait, identification of the causative
gene/mutation. and characterization of a similarly short sleep phenotype in modeled mice (and a corresponding
rest-activity phenotype in Drosophila). We have since identified over 90 FNSS probands and have been
expanding these families with phenotyping and DNA banking of additional affected and unaffected family
members. Subsequent whole exome sequencing (WES) identified 2 candidate genes/mutations (1 in each of 2
families). In both cases, we've generated mouse models of the human mutations. Both of these mice also show
short sleep phenotype as seen in human subjects. Another gene (GRM1) was found to harbor distinct mutations
in 2 different families. A mouse model of one GRM1 allele also shows short sleep by EEG. These 4 genes
(DEC2, ADRB1, NPSR1, and GRM1) still only explain a minority of the ~30 families that underwent initial WES.
In this proposal, we plan to continue collecting FNSS subjects from existing `unexplained' families and to continue
collecting new probands and their families. Our growing database is an incredible resource for identifying
additional FNSS genes/mutations via whole exome sequencing and whole genome sequencing. Studies of this
growing list of FNSS genes will help us and others to better understand pathways and brain circuits that
contribute to sleep regulation and efficiency. Ultimately, understanding of such biological pathways may lead to
novel targets for developing better drugs to improve sleep quality and efficiency.

## Key facts

- **NIH application ID:** 10212126
- **Project number:** 1R01NS117929-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** LOUIS J. PTACEK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $666,175
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212126

## Citation

> US National Institutes of Health, RePORTER application 10212126, Probing genetics and biology of human sleep homeostasis (1R01NS117929-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10212126. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*