GEO series

Somatic Mutations in MCOLN3 Are Associated with Aldosterone-Producing Adenomas

GSE299739 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2026/06/13 Platform GPL20301

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: 4 × Empty vector # vs 4 × MCOLN3 WT # vs 4 × MCOLN3 Y391D #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.

Summary (written by the submitters)

Background: Primary aldosteronism is a common but underdiagnosed cause of endocrine hypertension that contributes to global cardiovascular morbidity and mortality. It is characterized by renin-independent hyperaldosteronism that originates from adrenal lesions — the majority of which are found to harbor aldosterone-driver somatic mutations in genes encoding ion-transporting proteins.

Read the full summary ↓

These mutations disrupt intracellular calcium homeostasis, facilitating pathologic increase in aldosterone synthase (CYP11B2) expression and aldosterone production. Elucidating the exact mechanisms causing aldosterone excess in primary aldosteronism would further the development of targeted treatments and alleviate the global hypertension burden.Methods: Next-generation sequencing analysis of formalin-fixed paraffin-embedded aldosterone-producing adenomas identified novel somatic variants in MCOLN3 (encoding the cation-permeable channel, TRPML3). Electrophysiologic, fura-2 calcium measurements, gene expression and steroid quantification studies were performed in adrenal HAC15 cells to characterize the functional effects of the novel MCOLN3 mutations. Results: Three somatic MCOLN3 variants (p.Y391D, p.F415I and p.N411_V412delinsI) were identified in four aldosterone-producing adenomas from male primary aldosteronism patients. Mutated MCOLN3 expressed in HAC15 cells resulted in a gain-of-function phenotype, which induced cell membrane depolarization and calcium influx and, in turn, triggered a significant increase in aldosterone synthase expression and aldosterone production. Conclusions: This is the first report of disease-causing MCOLN3 mutations in humans and first to implicate mutated MCOLN3 as a driver of dysregulated aldosterone production in primary aldosteronism.

This dataset

Open GSE299739 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 GSE299739_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 PRJNA1276337 and SRA study SRP592088. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

4 × Empty vector # vs 4 × MCOLN3 WT # vs 4 × MCOLN3 Y391D #

Supports a between-group comparison across 12 samples.

How we read this: 3 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

GSM9045338 Empty vector #1 Empty vector #
GSM9045339 Empty vector #2 Empty vector #
GSM9045340 Empty vector #3 Empty vector #
GSM9045341 Empty vector #4 Empty vector #
GSM9045342 MCOLN3 WT #1 MCOLN3 WT #
GSM9045343 MCOLN3 WT #2 MCOLN3 WT #
GSM9045344 MCOLN3 WT #3 MCOLN3 WT #
GSM9045345 MCOLN3 WT #4 MCOLN3 WT #
GSM9045346 MCOLN3 Y391D #1 MCOLN3 Y391D #
GSM9045347 MCOLN3 Y391D #2 MCOLN3 Y391D #
GSM9045348 MCOLN3 Y391D #3 MCOLN3 Y391D #
GSM9045349 MCOLN3 Y391D #4 MCOLN3 Y391D #

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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.