Evidence map›Paper›PMID 40961184›Full record

ArticleScience advances2025

Mapping the genetic landscape of iron metabolism uncovers the SETD2 methyltransferase as a modulator of iron flux.

Anthony W Martinelli, Chun-Pei Wu, Tristan Vornbäumen, Hudson W Coates, Louise H Jordon, Niek Wit, Jia J Sia, Anneliese O Speak, James A Nathan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Anthony W MartinelliCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.ORCID 0000-0002-7285-7498
Chun-Pei WuCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.
Tristan VornbäumenCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.
Hudson W CoatesCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.ORCID 0000-0002-6506-5249
Louise H JordonCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.ORCID 0000-0002-0066-4750
Niek WitCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.ORCID 0009-0002-4330-5333
Jia J SiaCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.ORCID 0000-0003-4750-3417
Anneliese O SpeakCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.ORCID 0000-0003-4890-4685
James A NathanCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.ORCID 0000-0002-0248-1632

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cellular iron levels must be tightly regulated to ensure sufficient iron for essential enzymatic functions while avoiding the harmful generation of toxic species. Here, to better understand how iron levels are controlled, we carry out genome-wide mutagenesis screens in human cells. Alongside mapping known components of iron sensing, we determine the relative contributions of iron uptake, iron recycling, ferritin breakdown, and mitochondrial flux in controlling the labile iron pool. We also identify SETD2, a histone methyltransferase, as a chromatin modifying enzyme that controls intracellular iron availability through ferritin breakdown. Functionally, we show that SETD2 inhibition or cancer-associated

Indexed as

Histone-Lysine N-MethyltransferaseIronFerritinsFerroptosisHumansMitochondriaMutationFerritinsHistone-Lysine N-MethyltransferaseIronSETD2 protein, human

Identifiers

PMID40961184
PMCPMC12442849

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.