GEO series

Divergent signaling profiles in mTOR gain-of-function Smith-Kingsmore syndrome and TSC2 deficiency

GSE330231 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2026/05/11 Platform GPL34281

At a glance

RNA-seq (gene expression) · human · 12 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: 12 samples: 3 × mTOR R1480/1483, glucose depleted, 2h, vs 3 × WT, glucose depleted, 2h, vs 3 × TSC2 KO, glucose depleted 1.5h, rapamycin treated 2.5h, vs 3 × TSC2 KO, glucose depleted 2h,Groups 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: Divergent signaling profiles in mTOR gain-of-function Smith-Kingsmore syndrome (SKS) and TSC2 deficiencybioRxiv : the preprint server for biology · 2026

Summary (written by the submitters)

Smith-Kingsmore syndrome (SKS) is a rare neurodevelopmental disorder caused by gain-of-function mutations in MTOR, yet whether these mutations phenocopy TSC2 loss or establish a distinct signaling state remains unclear. Using quantitative proteomics, phosphoproteomics, and transcriptomics in isogenic cell models of SKS (MTORΔ4aa), TSC2 loss (TSC2–/–), and wild-type controls under glucose depletion and refeeding, we find that MTORΔ4aa and TSC2–/– cells occupy fundamentally distinct regulatory states.

Read the full summary ↓

TSC2–/– cells exhibit broad anabolic remodeling and a transcriptional program dominated by NF-κB- and STAT-driven inflammatory responses. MTORΔ4aa cells instead display enrichment of nuclear and RNA processing programs, E2F/MYC-driven transcription, and a constrained proteomic dynamic range across nutrient states. Phosphoproteomic analysis of MTORΔ4aa reveals rerouting of nutrient-responsive signaling toward MAPK/ERK- and Ca2+/CaMK-dependent pathways with limited canonical mTORC1/S6K1 engagement. These findings establish SKS as a signaling rewiring disorder distinct from classical mTORC1 hyperactivation, with implications for therapeutic targeting.

Published in

Divergent signaling profiles in mTOR gain-of-function Smith-Kingsmore syndrome (SKS) and TSC2 deficiency

Carlson CR, Shen Y, He H et al. · bioRxiv : the preprint server for biology 2026 · PMID 42182492 · doi:10.64898/2026.05.09.724025

This dataset

Open GSE330231 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 GSE330231_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 PRJNA1463188 and SRA study SRP698313. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42182492) ↗

Study design

3 × mTOR R1480/1483, glucose depleted, 2h, vs 3 × WT, glucose depleted, 2h, vs 3 × TSC2 KO, glucose depleted 1.5h, rapamycin treated 2.5h, vs 3 × TSC2 KO, glucose depleted 2h,

Supports a case/control comparison: 3 samples read as cases, 3 as controls.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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

GSM9721979 mTOR R1480/1483, glucose depleted, 2h, rep1 mTOR R1480/1483, glucos…
GSM9721980 mTOR R1480/1483, glucose depleted, 2h, rep2 mTOR R1480/1483, glucos…
GSM9721981 mTOR R1480/1483, glucose depleted, 2h, rep3 mTOR R1480/1483, glucos…
GSM9721982 WT, glucose depleted, 2h, rep1 WT, glucose depleted, 2…
GSM9721983 WT, glucose depleted, 2h, rep2 WT, glucose depleted, 2…
GSM9721984 WT, glucose depleted, 2h, rep3 WT, glucose depleted, 2…
GSM9721985 TSC2 KO, glucose depleted 1.5h, rapamycin treated 2.5h, rep1 TSC2 KO, glucose deplet…
GSM9721986 TSC2 KO, glucose depleted 1.5h, rapamycin treated 2.5h, rep2 TSC2 KO, glucose deplet…
GSM9721987 TSC2 KO, glucose depleted 1.5h, rapamycin treated 2.5h, rep3 TSC2 KO, glucose deplet…
GSM9721988 TSC2 KO, glucose depleted 2h, rep1 TSC2 KO, glucose deplet…
GSM9721989 TSC2 KO, glucose depleted 2h, rep2 TSC2 KO, glucose deplet…
GSM9721990 TSC2 KO, glucose depleted 2h, rep3 TSC2 KO, glucose deplet…

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