Evidence map›Paper›PMID 39975210›Full record

ArticlebioRxiv : the preprint server for biology2025

Multiplex, multimodal mapping of variant effects in secreted proteins.

Nicholas A Popp, Rachel L Powell, Melinda K Wheelock, Kristen J Holmes, Brendan D Zapp, Kathryn M Sheldon, Shelley N Fletcher, Xiaoping Wu, Shawn Fayer, Alan F Rubin and 5 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Nicholas A PoppDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.ORCID 0000-0001-9374-3070
Rachel L PowellDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Melinda K WheelockDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Kristen J HolmesDivision of Hematology and Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
Brendan D ZappDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Kathryn M SheldonDivision of Hematology and Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
Shelley N FletcherBloodworks Northwest, Seattle, WA, USA.
Xiaoping WuCell Marker Laboratory, Seattle Children's Hospital, Seattle, WA.
Shawn FayerDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Alan F RubinBioinformatics Division, WEHI, Parkville, VIC, AU.ORCID 0000-0003-1474-605X
Kerry W LannertDivision of Hematology and Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
Alexis T ChangDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
John P SheehanDivision of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Jill M JohnsenDivision of Hematology and Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
Douglas M FowlerDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.

Funding

Technology to understand genetic variant effects in contextRM1HG010461 · NHGRI · UNIVERSITY OF WASHINGTON · PI Douglas M Fowler, Bruce Colston Trapnell · 2019 to 2026
$18.9M
The Center for Actionable Variant Analysis; measuring variant function at scaleUM1HG011969 · NHGRI · UNIVERSITY OF WASHINGTON · PI Douglas M Fowler, Lea Starita · 2021 to 2026
$9.9M
Large-Scale Methods for Assessing the Consequences of Mutations in ProteinsR01GM109110 · NIGMS · UNIVERSITY OF WASHINGTON · PI FOWLER, DOUGLAS M · 2014 to 2021
$2.4M
Comprehensive Characterization of Missense Mutants in Factor IXR01HL152066 · NHLBI · UNIVERSITY OF WASHINGTON · PI FOWLER, DOUGLAS M, JOHNSEN, JILL MARIE · 2020 to 2023
$1.8M
In Vivo Regulation of Factor IXa by Protein S in Hemophilia and Systemic HypercoagulabilityR01HL149855 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI SHEEHAN, JOHN PATRICK · 2020 to 2023
$1.5M
Comprehensive Characterization of Missense Variants in Factor IXF30HL151075 · NHLBI · UNIVERSITY OF WASHINGTON · PI POPP, NICHOLAS ANTHONY · 2020 to 2023
$178k
NHGRI NIH HHS RM1 HG010461NHGRI NIH HHS UM1 HG011969NHLBI NIH HHS F30 HL151075NHLBI NIH HHS R01 HL149855NHLBI NIH HHS R01 HL152066NIGMS NIH HHS R01 GM109110
6 · The paper itself

Abstract

Despite widespread advances in DNA sequencing, the functional consequences of most genetic variants remain poorly understood. Multiplexed Assays of Variant Effect (MAVEs) can measure the function of variants at scale, and are beginning to address this problem. However, MAVEs cannot readily be applied to the ~10% of human genes encoding secreted proteins. We developed a flexible, scalable human cell surface display method, Multiplexed Surface Tethering of Extracellular Proteins (MultiSTEP), to measure secreted protein variant effects. We used MultiSTEP to study the consequences of missense variation in coagulation factor IX (FIX), a serine protease where genetic variation can cause hemophilia B. We combined MultiSTEP with a panel of antibodies to detect FIX secretion and post-translational modification, measuring a total of 44,816 effects for 436 synonymous variants and 8,528 of the 8,759 possible missense variants. 49.6% of possible

Identifiers

PMID39975210
PMCPMC11838247

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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.