MorPhiC Consortium: towards functional characterization of all human genes

Mazhar Adli (), Laralynne Przybyla, Tony Burdett, Paul W. Burridge, Pilar Cacheiro, Howard Y. Chang, Jesse M. Engreitz, Luke A. Gilbert, William J. Greenleaf, Li Hsu, Danwei Huangfu, Ling-Hong Hung, Anshul Kundaje, Sheng Li, Helen Parkinson, Xiaojie Qiu, Paul Robson, Stephan C. Schürer, Ali Shojaie, William C. Skarnes, Damian Smedley, Lorenz Studer, Wei Sun, Dušica Vidović, Thomas Vierbuchen, Brian S. White, Ka Yee Yeung, Feng Yue and Ting Zhou
Additional contact information
Mazhar Adli: Feinberg School of Medicine
Laralynne Przybyla: University of California
Tony Burdett: European Molecular Biology Laboratory
Paul W. Burridge: Feinberg School of Medicine
Pilar Cacheiro: Queen Mary University of London
Howard Y. Chang: Stanford University
Jesse M. Engreitz: Stanford University
Luke A. Gilbert: University of California
William J. Greenleaf: Stanford University
Li Hsu: Fred Hutchinson Cancer Center
Danwei Huangfu: Sloan Kettering Institute
Ling-Hong Hung: University of Washington Tacoma
Anshul Kundaje: Stanford University
Sheng Li: The Jackson Laboratory for Genomic Medicine
Helen Parkinson: European Molecular Biology Laboratory
Xiaojie Qiu: Stanford University
Paul Robson: The Jackson Laboratory for Genomic Medicine
Stephan C. Schürer: University of Miami
Ali Shojaie: University of Washington
William C. Skarnes: The Jackson Laboratory for Genomic Medicine
Damian Smedley: Queen Mary University of London
Lorenz Studer: Sloan Kettering Institute
Wei Sun: Fred Hutchinson Cancer Center
Dušica Vidović: University of Miami
Thomas Vierbuchen: Sloan Kettering Institute
Brian S. White: The Jackson Laboratory for Genomic Medicine
Ka Yee Yeung: University of Washington Tacoma
Feng Yue: Feinberg School of Medicine
Ting Zhou: Sloan Kettering Institute

Nature, 2025, vol. 638, issue 8050, 351-359

Abstract: Abstract Recent advances in functional genomics and human cellular models have substantially enhanced our understanding of the structure and regulation of the human genome. However, our grasp of the molecular functions of human genes remains incomplete and biased towards specific gene classes. The Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Consortium aims to address this gap by creating a comprehensive catalogue of the molecular and cellular phenotypes associated with null alleles of all human genes using in vitro multicellular systems. In this Perspective, we present the strategic vision of the MorPhiC Consortium and discuss various strategies for generating null alleles, as well as the challenges involved. We describe the cellular models and scalable phenotypic readouts that will be used in the consortium’s initial phase, focusing on 1,000 protein-coding genes. The resulting molecular and cellular data will be compiled into a catalogue of null-allele phenotypes. The methodologies developed in this phase will establish best practices for extending these approaches to all human protein-coding genes. The resources generated—including engineered cell lines, plasmids, phenotypic data, genomic information and computational tools—will be made available to the broader research community to facilitate deeper insights into human gene functions.

Date: 2025
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DOI: 10.1038/s41586-024-08243-w

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