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BIRC3 (encoding cIAP2) variants are associated with Crohn’s Disease.

GSE299375 Danio rerio (zebrafish) RNA-seq (gene expression) 33 samples Submitted 2026/07/15 Platform GPL34290Platform GPL24995
At a glance

RNA-seq (gene expression) · zebrafish · 33 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
Danio rerio (zebrafish)
Samples
33 samples: 11 conditions, mostly in triplicateGroups 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
BIRC3 (Encoding cIAP2) Variants Result in Dysregulated RIPK1 Signaling Leading to Increased Epithelial Cell Death and Are Associated With Monogenic Crohn's DiseaseGastroenterology · 2026
Summary (written by the submitters)
The baculoviral IAP repeat-containing 3 (BIRC3) gene encodes the Cellular Inhibitor of Apoptosis Protein 2 (cIAP2) a regulator of innate immune pathways including TNFα receptor signaling. We identified 5 heterozygous and 3 homozygous rare damaging BIRC3 variants in 13 patients from 9 independent families who presented with Crohn’s Disease (CD) between 2 months and 31 years of age.
Read the full summary ↓
A knock-in mouse model of the BIRC3 variant (cIAP2H312Y/+) identified in two independent CD families had increased susceptibility to DSS-induced colitis and ciap−/+ zebrafish developed spontaneous colitis. Transcriptome analysis showed that reduced BIRC3 expression led to the induction of several TNFa responsive genes including NFKB2. Functional studies showed that all cIAP2 variants had impaired inhibition of NFκB2 activity and increased cell death when induced by TNFa. Finally, cIAP2H312Y/+ mice treated with apoptosis or RIPK1 inhibitors had improved clinical outcomes. Our study demonstrates that BIRC3 variants results in dysregulation of NFκB2 signaling leading to in CD.
Published in
BIRC3 (Encoding cIAP2) Variants Result in Dysregulated RIPK1 Signaling Leading to Increased Epithelial Cell Death and Are Associated With Monogenic Crohn's Disease
Li Q, Nambu R, Yaqiang H et al. · Gastroenterology 2026 · PMID 42335979 · doi:10.1053/j.gastro.2026.05.022
This dataset
Open GSE299375 in finder → Find more 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 GSE299375_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 PRJNA1274021 and SRA study SRP590869. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42335979) ↗
Study design
11 conditions, mostly in triplicate
Mus_musculus-312HZ-Ctrl ×3 Mus_musculus-312HZ-TNF ×3 Mus_musculus-BKO-Ctrl ×3 Mus_musculus-BKO-TNF ×3 Mus_musculus-WT-Ctrl ×3 Mus_musculus-WT-TNF ×3 zebrafish-wt-tc-3d ×3 zebrafish-birc3-het-tc-3d ×3 +3 more

Supports a between-group comparison across 33 samples.

How we read this: 11 replicated groups read from 33 sample titles; they account for 33 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
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