# Gene Interaction in Development and Disease

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $78,760

## Abstract

Abstract
We identified the uncharacterized human gene C10orf35 (FAM214B) in two genome-wide screens: a
suppressor screen for genes whose overexpression corrects the enlarged lysosomes in FIG4 null cells, and a
knock-out screen for genes whose inactivation in wildtype cells produces enlarged lysosomes. C10orf35 was a
positive hit in both screens, providing strong evidence for a role in lysosome biology. To define the
physiological function of C10orf35, we generated a knock-out allele of the mouse ortholog. In this supplemental
project, we will characterize the function of C10orf35 by generating homozygous null mice and examining
survival, tissue morphology, and lysosome function in cultured mouse embryonic fiboblasts. We will also
characterize a C10orf35 variant of unknown significance that was identified through Genematcher in a patient
with spastic paraplegia. We will evaluate the ability of the missense variant of unknown significance by
transfection of a C10orf35 null HAP1 cell line. C10orf35 is a member of a two-gene family. We generated a null
allele of the other mouse family member, C4orf32. We will characterize the phenotype of this null mouse as per
above. We will also generate double homozygotes missing both genes, to evaluate the essentiality of this
gene family for mammalian survival. This work will provide novel information about a previously
uncharacterized gene family in the human genome that is known to be related to lysosome function. The
requisite methods and reagents are available in the laboratory. Quinlan Doctrove is a member of an
underrepresented minority. He will work closely with a senior researcher who has fourteen years of experience
in related projects. This project will provide an opportunity for training in current methods for characterization of
the human genome, including characterization of mouse models and functional analysis of pathogenic variants.

## Key facts

- **NIH application ID:** 10610535
- **Project number:** 3R01GM024872-45S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** MIRIAM H MEISLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $78,760
- **Award type:** 3
- **Project period:** 1977-06-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10610535

## Citation

> US National Institutes of Health, RePORTER application 10610535, Gene Interaction in Development and Disease (3R01GM024872-45S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10610535. Licensed CC0.

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