GEO series

Encephalopathy-linked UFM1 variants impede neuronal protein translation, development and function

GSE299278 Mus musculus (mouse) RNA-seq (gene expression) 18 samples Submitted 2026/04/22 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 18 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 18 samples: 9 × RFP sample vs 9 × CRE sampleGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Encephalopathy-linked UFM1 variants impede neuronal protein translation, development, and functionEMBO molecular medicine · 2026

Summary (written by the submitters)

Genetic variants that hinder post-translational protein modifications by UFM1, UFMylation, cause encephalopathies. UFMylation regulates endoplasmic reticulum (ER) homeostasis, but how UFMylation-deficiencies cause selective neurological defects is unknown. Using Ufm1 knock-out mice, we investigated two types of UFMylation pathologies, UFM1 loss and expression of a pathogenic UFM1-R81C variant.

Read the full summary ↓

We found that UFM1-deficiency confounds neuron development and synapse function. Mechanistically, UFM1 loss is associated with induction of ER stress, activation of the PERK-UPR pathway, and reduced protein translation. These defects are rescued by wild-type UFM1, but only partially by UFM1-R81C. UFM1-deficient and UFM1-R81Cexpressing neurons display distinct responses to ER stress, indicating that UFM1-R81C is not merely a loss-of-function variant. Exploring therapeutic options, we show that the PERK-UPR inhibitor Trazodone restores protein translation solely in UFM1-R81C-expressing neurons, and increases synapse number. Our study unveils a pivotal role for UFMylation in neuronal development, provides a molecular understanding of the signaling mechanisms altered in UFM1- associated encephalopathies, and offers important insights into potential treatments for these Genetic variants that hinder post-translational protein modifications by UFM1, UFMylation, cause encephalopathies. UFMylation regulates endoplasmic reticulum (ER) homeostasis, but how UFMylation-deficiencies cause selective neurological defects is unknown. Using Ufm1 knock-out mice, we investigated two types of UFMylation pathologies, UFM1 loss and expression of a pathogenic UFM1-R81C variant. We found that UFM1-deficiency confounds neuron development and synapse function. Mechanistically, UFM1 loss is associated with induction of ER stress, activation of the PERK-UPR pathway, and reduced protein translation. These defects are rescued by wild-type UFM1, but only partially by UFM1-R81C. UFM1-deficient and UFM1-R81C-expressing neurons display distinct responses to ER stress, indicating that UFM1-R81C is not merely a loss-of-function variant. Exploring therapeutic options, we show that the PERK-UPR inhibitor Trazodone restores protein translation solely in UFM1-R81C-expressing neurons, initiating an increase in synapse number. Our study unveils a pivotal role for UFMylation in neuronal development and provides a molecular understanding of the signaling mechanisms altered in UFM1-associated encephalopathies, offering valuable insights into potential treatments for these disorders.

Published in

Encephalopathy-linked UFM1 variants impede neuronal protein translation, development, and function

Perdigão C, Torres J, Magnussen HM et al. · EMBO molecular medicine 2026 · PMID 41731076 · doi:10.1038/s44321-026-00389-6

This dataset

Open GSE299278 in finder → Find more mouse RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE299278_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1273747 and SRA study SRP591910. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41731076) ↗

Study design

9 × RFP sample vs 9 × CRE sample

Supports a between-group comparison across 18 samples.

How we read this: 2 replicated groups read from 18 sample titles; they account for 18 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM9036543 RFP sample 1 RFP sample
GSM9036544 RFP sample 2 RFP sample
GSM9036545 RFP sample 3 RFP sample
GSM9036546 CRE sample 1 CRE sample
GSM9036547 CRE sample 2 CRE sample
GSM9036548 CRE sample 3 CRE sample
GSM9036549 RFP sample 4 RFP sample
GSM9036550 CRE sample 4 CRE sample
GSM9036551 CRE sample 5 CRE sample
GSM9036552 RFP sample 5 RFP sample
GSM9036553 RFP sample 6 RFP sample
GSM9036554 CRE sample 6 CRE sample
GSM9036555 RFP sample 7 RFP sample
GSM9036556 CRE sample 7 CRE sample
GSM9036557 CRE sample 8 CRE sample
GSM9036558 RFP sample 8 RFP sample
GSM9036559 RFP sample 9 RFP sample
GSM9036560 CRE sample 9 CRE sample

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