GEO series

Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans

GSE267600 Homo sapiens (human) RNA-seq (gene expression) 30 samples Submitted 2024/11/24 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 30 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: 30 samples: 22 distinct titles, 2 of them repeatedGroups 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: Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humansThe Journal of experimental medicine · 2025

Summary (written by the submitters)

IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. The absence of IKKα causes fetal encasement syndrome in humans, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and causes combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features.

Read the full summary ↓

We showed that both variants were loss-of-function. Non-canonical NF-κB activation was profoundly diminished in stromal and immune cells while the canonical pathway was unexpectedly partially impaired. Reintroducing wt CHUK restored non-canonical NF-κB activation. The patient had neutralizing autoantibodies against type I IFN, akin to non-canonical NF-κB pathway deficiencies. Thus, this is the first case of biallelic CHUK mutations disrupting IKKα kinase function, broadening non-canonical NF-κB defect understanding, and suggesting IKKα's role in canonical NF-κB target gene expression in humans.

Published in

Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans

Riller Q, Sorin B, Courteille C et al. · The Journal of experimental medicine 2025 · PMID 39812688 · doi:10.1084/jem.20240843

This dataset

Open GSE267600 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 GSE267600_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 PRJNA1111916 and SRA study SRP507974. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39812688) ↗

Study design

22 distinct titles, 2 of them repeated

C HMW 10 ug/mL 6h, ×5 C HMW 10 ug/mL, ×5

Supports a case/control comparison: 8 samples read as cases, 8 as controls.

How we read this: Read from 30 sample titles: 22 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

GSM8270013 1A_R1, NEMO_null, no stimulation, rep1
GSM8270014 1Abis_R1, NEMO_null, no stimulation, rep2
GSM8270015 1B_R1, NEMO_null, TNFa 10 ng/mL 6h, rep1
GSM8270016 1Bbis_R1, NEMO_null, TNFa 10 ng/mL 6h, rep2
GSM8270017 1C_R1, NEMO_null, poly I:C HMW 10 ug/mL 6h, rep1
GSM8270018 1Cbis_R1, NEMO_null, poly I:C HMW 10 ug/mL, rep2
GSM8270019 3A_R1, CTL1, no stimulation, rep1
GSM8270020 3Abis_R1, CTL1, no stimulation, rep2
GSM8270021 3B_R1, CTL1, TNFa 10 ng/mL 6h, rep1
GSM8270022 3Bbis_R1, CTL1, TNFa 10 ng/mL 6h, rep2
GSM8270023 3C_R1, CTL1, poly I:C HMW 10 ug/mL 6h, rep1
GSM8270024 3Cbis_R1, CTL1, poly I:C HMW 10 ug/mL, rep2
GSM8270025 8A_R1, CHUK patient, no stimulation, rep1
GSM8270026 8Abis_R1, CHUK patient, no stimulation, rep2
GSM8270027 8B_R1, CHUK patient, TNFa 10 ng/mL 6h, rep1
GSM8270028 8Bbis_R1, CHUK patient, TNFa 10 ng/mL 6h, rep2
GSM8270029 8C_R1, CHUK patient, poly I:C HMW 10 ug/mL 6h, rep1
GSM8270030 8Cbis_R1, CHUK patient, poly I:C HMW 10 ug/mL, rep2
GSM8270031 9A_R1, NFKB2 patient, no stimulation, rep1
GSM8270032 9Abis_R1, NFKB2 patient, no stimulation, rep2
GSM8270033 9B_R1, NFKB2 patient, TNFa 10 ng/mL 6h, rep1
GSM8270034 9Bbis_R1, NFKB2 patient, TNFa 10 ng/mL 6h, rep2
GSM8270035 9C_R1, NFKB2 patient, poly I:C HMW 10 ug/mL 6h, rep1
GSM8270036 9Cbis_R1, NFKB2 patient, poly I:C HMW 10 ug/mL, rep2
GSM8270037 12A_R1, CTL2, no stimulation, rep1
GSM8270038 12Abis_R1, CTL2, no stimulation, rep2
GSM8270039 12B_R1, CTL2, TNFa 10 ng/mL 6h, rep1
GSM8270040 12Bbis_R1, CTL2, TNFa 10 ng/mL 6h, rep2
GSM8270041 12C_R1, CTL2, poly I:C HMW 10 ug/mL 6h, rep1
GSM8270042 12Cbis_R1, CTL2, poly I:C HMW 10 ug/mL, rep2

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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.