Evidence map›Paper›PMID 39962238›Full record

ArticleNature genetics2025

Functional analysis of cancer-associated germline risk variants.

Laura N Kellman, Poornima H Neela, Suhas Srinivasan, Zurab Siprashvili, Ronald L Shanderson, Audrey W Hong, Deepti Rao, Douglas F Porter, David L Reynolds, Robin M Meyers and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
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  4. Review
  5. Article
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  9. Review
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

27 authors.

Laura N KellmanProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-1073-8936
Poornima H NeelaProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Suhas SrinivasanProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8309-9648
Zurab SiprashviliProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Ronald L ShandersonProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-9702-2972
Audrey W HongProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Deepti RaoProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Douglas F PorterProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
David L ReynoldsProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Robin M MeyersProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Margaret G GuoProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-7713-3846
Xue YangProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Yang ZhaoProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Glenn G WozniakProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Laura K H DonohueProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-1346-2840
Rajani ShenoyProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Lisa A KoProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-3732-0580
Duy T NguyenProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Smarajit MondalProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-2883-2728
Omar S GarciaProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Lara E ElcavageProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Ibtihal ElfakiProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-9951-9974
Nathan S AbellDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Shiying TaoProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Christopher M LopezProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Stephen B MontgomeryDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-5200-3903
Paul A KhavariProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA. khavari@stanford.edu.ORCID http://orcid.org/0000-0003-0098-4989

Funding

Mechanisms of Epidermal Homeostasis and Early NeoplasiaR01AR043799 · NIAMS · STANFORD UNIVERSITY · PI PAUL KHAVARI · 1998 to 2026
$9.1M
Regulatory Variants in HUMAN SKIN DISEASESR01AR076965 · NIAMS · STANFORD UNIVERSITY · PI PAUL KHAVARI · 2020 to 2026
$3.6M
Regulators of TumorigenesisR01CA142635 · NCI · STANFORD UNIVERSITY · PI KHAVARI, PAUL · 2011 to 2020
$3.5M
Atlas of Regulatory Variants in Diseases (ARVID)U24HG010856 · NHGRI · STANFORD UNIVERSITY · PI KHAVARI, PAUL · 2020 to 2024
$3.3M
NCI NIH HHS R01 CA142635NHGRI NIH HHS U24 HG010856NIAMS NIH HHS R01 AR043799NIAMS NIH HHS R01 AR076965
6 · The paper itself

Abstract

Single-nucleotide variants (SNVs) in regulatory DNA are linked to inherited cancer risk. Massively parallel reporter assays of 4,041 SNVs linked to 13 neoplasms comprising >90% of human malignancies were performed in pertinent primary human cell types and then integrated with matching chromatin accessibility, DNA looping and expression quantitative trait loci data to nominate 380 potentially regulatory SNVs and their putative target genes. The latter highlighted specific protein networks in lifetime cancer risk, including mitochondrial translation, DNA damage repair and Rho GTPase activity. A CRISPR knockout screen demonstrated that a subset of germline putative risk genes also enables the growth of established cancers. Editing one SNV, rs10411210 , showed that its risk allele increases rhophilin RHPN2 expression and stimulus-responsive RhoA activation, indicating that individual SNVs may upregulate cancer-linked pathways. These functional data are a resource for variant prioritization efforts and further interrogation of the mechanisms underlying inherited risk for cancer.

Indexed as

Genetic Predisposition to DiseaseGerm-Line MutationNeoplasmsPolymorphism, Single NucleotideAdaptor Proteins, Signal TransducingHumansQuantitative Trait LociAdaptor Proteins, Signal Transducing

Identifiers

PMID39962238
PMCPMC13147685

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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.