GEO series

Multiple sclerosis severity variant in the DYSF–ZNF638 locus associates with increased neuronal loss and inflammation

GSE273954 Homo sapiens (human) RNA-seq (gene expression) 26 samples Submitted 2025/03/28 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 26 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: Homo sapiens (human)
Samples: 26 samples: 26 samples, each with a distinct title — no replicated groupsGroups 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: Multiple sclerosis severity variant in DYSF-ZNF638 locus associates with neuronal loss and inflammationiScience · 2025

Summary (written by the submitters)

A recent genome-wide association study identified homozygous carriership of the A allele at variant rs10191329 to associate with faster disability accrual in multiple sclerosis (MS). We investigated the impact of rs10191329AA carriership on MS pathology in the Netherlands Brain Bank MS cohort (n=290) and explored its impact on neuro-axonal damage, lymphocyte accumulation, and protein expression of the flanking genes dysferlin (DYSF) and zinc finger protein 638 (ZNF638) by comparing homozygous carriers (n=6) to non-carriers (rs10191329CC; n=12).

Read the full summary ↓

Homozygous carriership associated with more amyloid precursor protein (APP)+ bulbs/axons, reflecting increased acute axonal stress, in normal-appearing white matter (NAWM) and white matter lesions, as well as with reduced neuronal density in cortical normal-appearing grey matter (NAGM). Further, homozygous carriers showed a higher proportion of active and mixed active/inactive lesions with foamy microglia, which associate with higher cerebrospinal fluid neurofilament light chain levels. DYSF and ZNF638 were expressed by neurons and oligodendrocytes. In homozygous carriers, NAWM was characterized by a higher proportion of ZNF638+ oligodendrocytes, and NAGM showed more DYSF+ cells. Unexpectedly, nuclear RNA sequencing did not show changes in DYSF or ZNF638 expression in oligodendrocytes and neurons but rather an upregulation of mitochondrial genes in homozygous carriers, specifically those associated with Leber’s hereditary optic neuropathy (LHON), a mitochondrial disease that can have a mechanistic interaction with MS. These data suggest that the association between MS severity and rs10191329 may be driven by increased susceptibility to neurodegeneration, demyelination, and chronic inflammatory lesions. Further understanding of the role of DYSF and ZNF638 as well as LHON-associated mitochondrial pathways in MS pathology may reveal new therapeutic targets to attenuate MS progression.

Published in

Multiple sclerosis severity variant in DYSF-ZNF638 locus associates with neuronal loss and inflammation

Engelenburg HJ, van den Bosch AMR, Chen JQA et al. · iScience 2025 · PMID 40352730 · doi:10.1016/j.isci.2025.112430

This dataset

Open GSE273954 in finder → Find more human 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 GSE273954_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 PRJNA1144146 and SRA study SRP524139. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40352730) ↗

Study design

26 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 26 sample titles: 26 distinct titles with little repetition. 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

GSM8440314 NeuN, D1, AA
GSM8440315 NeuN, D2, CC
GSM8440316 NeuN, D3, CC
GSM8440317 NeuN, D4, CC
GSM8440318 NeuN, D5, CC
GSM8440319 NeuN, D6, AA
GSM8440320 NeuN, D7, CC
GSM8440321 NeuN, D8, AA
GSM8440322 NeuN, D9, CC
GSM8440323 NeuN, D10, AA
GSM8440324 NeuN, D11, CC
GSM8440325 NeuN, D12, CC
GSM8440326 NeuN, D13, AA
GSM8440327 Olig2, D1, AA
GSM8440328 Olig2, D2, CC
GSM8440329 Olig2, D3, CC
GSM8440330 Olig2, D4, CC
GSM8440331 Olig2, D5, CC
GSM8440332 Olig2, D6, AA
GSM8440333 Olig2, D7, CC
GSM8440334 Olig2, D8, AA
GSM8440335 Olig2, D9, CC
GSM8440336 Olig2, D10, AA
GSM8440337 Olig2, D11, CC
GSM8440338 Olig2, D12, CC
GSM8440339 Olig2, D13, AA

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.