. 2025 Feb;638(8050):351-359.

doi: 10.1038/s41586-024-08243-w. Epub 2025 Feb 12.

MorPhiC Consortium: towards functional characterization of all human genes

Mazhar Adli^#¹, Laralynne Przybyla^#², Tony Burdett³, Paul W Burridge⁴, Pilar Cacheiro⁵, Howard Y Chang⁶, Jesse M Engreitz^{7

8}, Luke A Gilbert⁹, William J Greenleaf⁷, Li Hsu¹⁰, Danwei Huangfu¹¹, Ling-Hong Hung¹², Anshul Kundaje¹³, Sheng Li¹⁴, Helen Parkinson¹⁵, Xiaojie Qiu^{8

13}, Paul Robson¹⁴, Stephan C Schürer¹⁶, Ali Shojaie¹⁷, William C Skarnes¹⁴, Damian Smedley⁵, Lorenz Studer¹¹, Wei Sun¹⁰, Dušica Vidović¹⁶, Thomas Vierbuchen¹¹, Brian S White¹⁴, Ka Yee Yeung¹², Feng Yue¹⁸, Ting Zhou¹¹; MorPhiC Consortium

Collaborators, Affiliations

Collaborators

MorPhiC Consortium:
Neda Abbaszadeh, Juliana Alcoforado Diniz, Anahita Amiri, Rohan N V S R K Avireddy, Tao Bai, Dylan S Baker, Jacob J Baroch, Chia Chan, Sijie Chen, Xintong Chen, Hyein S Cho, Anshul Choudhary, Caty E Chung, Thomas J Dahlstrom, Anthony Doty, Basak Eraslan, Adam L Felsenfeld, Patrick J Fleming, Colin F Fletcher, Jesse Flores, William F Flynn, Yihao Fu, Bryce Nobutoshi Fukuda, Jessica L Garofalo, Rachel A Glenn, Juhee Goyal, Alexandra M Griffiths, Tingfeng Guo, Revant Gupta, Dipayan Gupta, Nan Hu, Yung-Hsin Huang, Aaron J Huebner, Carolyn Hutter, Angelina Kendra, Gina Kirsammer, Orges A Koci, Katerina Kraft, Zhaoheng Li, Shuzhao Li, Si Liu, Zukai Liu, Dingyu Liu, Nianping Liu, Renhe Luo, Davi Lyra Leite, Yuzhen Mao, Gabriel Marengo, Justin A McDonough, Adrian Melo-Carrillo, Chen Meng, Eyal Metzl-Raz, Joshua M Mitchell, Varun Mittal, Niharika Nasam, Ozlem Neyisci, Gang Ning, Devon Parker, Marcin Pilarczyk, Ajay Pillai, Olivier B Poirion, Praeploy Pongpamorn, Arushi Rana, Jamilex Rivera-Diaz, Nicolette C Ross, Enrique Sapena Ventura, Fidan Seker, Kaustav Sengupta, Anu Shivalikanjli, Wenzhuo Tang, Denis Torre, Ping Wang, Xianming Wang, De Xing, Dapeng Yang, Galabina N Yordanova, Bo Yu, Tony Zeng, Stephen Zhang, Zhehao Zhang, Nan Zhang, Hengqiang Zhao, Shujian Zheng, Aaron Zhong, Justina Žurauskienė

Affiliations

¹ Robert H. Lurie Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. adli@northwestern.edu.
² Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.
³ Omics Section, European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Hinxton, UK.
⁴ Department of Pharmacology, Center for Pharmacogenomics, Northwestern University, Feinberg School of Medicine, Evanston, IL, USA.
⁵ William Harvey Research Institute, Clinical Pharmacology and Precision Medicine, Queen Mary University of London, London, UK.
⁶ Department of Dermatology, Stanford University, Stanford, CA, USA.
⁷ Department of Genetics, Stanford University, Stanford, CA, USA.
⁸ Basic Science and Engineering (BASE) Initiative, Stanford University, Stanford, CA, USA.
⁹ Department of Urology, University of California, San Francisco, CA, USA.
¹⁰ Department of Biostatistics, Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹¹ Developmental Biology Program, Sloan Kettering Institute, New York, NY, USA.
¹² School of Engineering and Technology, University of Washington Tacoma, Tacoma, WA, USA.
¹³ Departments of Genetics and Computer Science, Stanford University, Stanford, CA, USA.
¹⁴ The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
¹⁵ Knowledge Management Section, European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Hinxton, UK.
¹⁶ Molecular and Cellular Pharmacology; Sylvester Comprehensive Cancer Center, University of Miami, Coral Gables, FL, USA.
¹⁷ Department of Biostatistics, University of Washington, Seattle, WA, USA.
¹⁸ Department of Biochemistry and Molecular Genetics, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.

^# Contributed equally.

PMID: 39939790
PMCID: PMC12088665
DOI: 10.1038/s41586-024-08243-w

MorPhiC Consortium: towards functional characterization of all human genes

Mazhar Adli et al. Nature. 2025 Feb.

. 2025 Feb;638(8050):351-359.

doi: 10.1038/s41586-024-08243-w. Epub 2025 Feb 12.

Authors

Collaborators

MorPhiC Consortium:
Neda Abbaszadeh, Juliana Alcoforado Diniz, Anahita Amiri, Rohan N V S R K Avireddy, Tao Bai, Dylan S Baker, Jacob J Baroch, Chia Chan, Sijie Chen, Xintong Chen, Hyein S Cho, Anshul Choudhary, Caty E Chung, Thomas J Dahlstrom, Anthony Doty, Basak Eraslan, Adam L Felsenfeld, Patrick J Fleming, Colin F Fletcher, Jesse Flores, William F Flynn, Yihao Fu, Bryce Nobutoshi Fukuda, Jessica L Garofalo, Rachel A Glenn, Juhee Goyal, Alexandra M Griffiths, Tingfeng Guo, Revant Gupta, Dipayan Gupta, Nan Hu, Yung-Hsin Huang, Aaron J Huebner, Carolyn Hutter, Angelina Kendra, Gina Kirsammer, Orges A Koci, Katerina Kraft, Zhaoheng Li, Shuzhao Li, Si Liu, Zukai Liu, Dingyu Liu, Nianping Liu, Renhe Luo, Davi Lyra Leite, Yuzhen Mao, Gabriel Marengo, Justin A McDonough, Adrian Melo-Carrillo, Chen Meng, Eyal Metzl-Raz, Joshua M Mitchell, Varun Mittal, Niharika Nasam, Ozlem Neyisci, Gang Ning, Devon Parker, Marcin Pilarczyk, Ajay Pillai, Olivier B Poirion, Praeploy Pongpamorn, Arushi Rana, Jamilex Rivera-Diaz, Nicolette C Ross, Enrique Sapena Ventura, Fidan Seker, Kaustav Sengupta, Anu Shivalikanjli, Wenzhuo Tang, Denis Torre, Ping Wang, Xianming Wang, De Xing, Dapeng Yang, Galabina N Yordanova, Bo Yu, Tony Zeng, Stephen Zhang, Zhehao Zhang, Nan Zhang, Hengqiang Zhao, Shujian Zheng, Aaron Zhong, Justina Žurauskienė

Affiliations

¹ Robert H. Lurie Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. adli@northwestern.edu.
² Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.
³ Omics Section, European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Hinxton, UK.
⁴ Department of Pharmacology, Center for Pharmacogenomics, Northwestern University, Feinberg School of Medicine, Evanston, IL, USA.
⁵ William Harvey Research Institute, Clinical Pharmacology and Precision Medicine, Queen Mary University of London, London, UK.
⁶ Department of Dermatology, Stanford University, Stanford, CA, USA.
⁷ Department of Genetics, Stanford University, Stanford, CA, USA.
⁸ Basic Science and Engineering (BASE) Initiative, Stanford University, Stanford, CA, USA.
⁹ Department of Urology, University of California, San Francisco, CA, USA.
¹⁰ Department of Biostatistics, Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹¹ Developmental Biology Program, Sloan Kettering Institute, New York, NY, USA.
¹² School of Engineering and Technology, University of Washington Tacoma, Tacoma, WA, USA.
¹³ Departments of Genetics and Computer Science, Stanford University, Stanford, CA, USA.
¹⁴ The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
¹⁵ Knowledge Management Section, European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Hinxton, UK.
¹⁶ Molecular and Cellular Pharmacology; Sylvester Comprehensive Cancer Center, University of Miami, Coral Gables, FL, USA.
¹⁷ Department of Biostatistics, University of Washington, Seattle, WA, USA.
¹⁸ Department of Biochemistry and Molecular Genetics, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.

^# Contributed equally.

PMID: 39939790
PMCID: PMC12088665
DOI: 10.1038/s41586-024-08243-w

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.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

**Figure 1:**
The dot plot shows the total number of publications per human gene based on a PubMed search where a gene symbol appears in the abstract or main text of all published articles. Dr. Matthew Hirschey (Duke University) kindly provided the code for the figure.

**Figure 2:**
The schematics show general experimental strategies for null allele generation and main cellular and molecular assays to characterize phenotypes of null alleles. The figure was originally created by Daryl Leja and modified by Mazhar Adli. Circled numbers indicate DPCs.

**Figure 3:**
The schematics compare the main experimental strategies the MorPhiC team will use for null allele generation. * There may be cases where all isoforms may be degron tagged, or degron may critically alter the gene function

See this image and copyright information in PMC

References

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MorPhiC Consortium: towards functional characterization of all human genes

Collaborators

Affiliations

MorPhiC Consortium: towards functional characterization of all human genes

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous