MorPhiC Consortium: towards functional characterization of all human genes.
Document Type
Article
Publication Date
2-1-2025
Original Citation
Adli M,
Przybyla L,
Burdett T,
Burridge P,
Cacheiro P,
Chang H,
Engreitz J,
Gilbert L,
Greenleaf W,
Hsu L,
Huangfu D,
Hung L,
Kundaje A,
Li S,
Parkinson H,
Qiu X,
Robson P,
Schürer S,
Shojaie A,
Skarnes W,
Smedley D,
Studer L,
Sun W,
Vidović D,
Vierbuchen T,
White B,
Yeung K,
Yue F,
Zhou T,
.
MorPhiC Consortium: towards functional characterization of all human genes. Nature. 2025;638(8050):351-9.
Keywords
JGM, Humans, Phenotype, Alleles, Genome, Human, Genomics
JAX Source
Nature. 2025;638(8050):351-9.
ISSN
1476-4687
PMID
39939790
DOI
https://doi.org/10.1038/s41586-024-08243-w
Grant
The MorPhiC Consortium is funded by the NHGRI MorPhiC Initiative (UM1HG012649, UM1HG012654, UM1HG012651, UM1 HG012660, U24HG012674, U01HG013176, U01HG013177 and U01HG013175).
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.