ArticleThe Journal of experimental medicine2021
GIMAP5 maintains liver endothelial cell homeostasis and prevents portal hypertension.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Systematic Review of Interleukin-35 in Endothelial Dysfunction: A New Target for Therapeutic Intervention.Mediators of inflammation · 2025Pooled it
- Overview of Non-Cirrhotic Portal Hypertension in Pediatric Patients.Journal of clinical medicine · 2026Review
- Genetic testing in liver diseases: Clinical applications.JHEP reports : innovation in hepatology · 2026Review
- GATA binding protein 4: Emerging role in liver development and diseases.Molecular biology reports · 2026Review
- Dynamic remodeling of portal vessels by Clec4g+ endothelial cells in liver growth and homeostasis.JCI insight · 2026Article
- Unexpected genetically determined immune dysregulation with liver involvement: GIMAP5 therapeutic dilemmas between targeted therapy and HSCT.Frontiers in immunology · 2026Article
- Single-cell multi-omics data reveal heterogeneity in liver tissue microenvironment induced by hypertension.Molecular therapy. Nucleic acids · 2025Article
- Angiocrine signaling in sinusoidal homeostasis and liver diseases.Journal of hepatology · 2024Review
- Liver sinusoidal endothelial cells contribute to portal hypertension through collagen type IV-driven sinusoidal remodeling.JCI insight · 2024Article
- Genetics of liver disease in adults.Hepatology communications · 2024Review
- GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway.Nature immunology · 2024Article
- When ceramides meet immune senescence, a GIMAP5 connection.Nature immunology · 2024Article
- Essential role of MFSD1-GLMP-GIMAP5 in lymphocyte survival and liver homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The diagnostic yield of exome sequencing in liver diseases from a curated gene panel.Scientific reports · 2023Article
- Hepatology Genome Rounds: An interdisciplinary approach to integrate genomic data into clinical practice.Journal of hepatology · 2023Review
- Angiocrine Signaling in Sinusoidal Health and Disease.Seminars in liver disease · 2023Review
- Clinical exome sequencing of 1000 families with complex immune phenotypes: Toward comprehensive genomic evaluations.The Journal of allergy and clinical immunology · 2022Review
- GIMAP6 regulates autophagy, immune competence, and inflammation in mice and humans.The Journal of experimental medicine · 2022Article
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Authors and funding
22 authors at 8 institutions in 3 countries.
Funding
Abstract
Portal hypertension is a major contributor to decompensation and death from liver disease, a global health problem. Here, we demonstrate homozygous damaging mutations in GIMAP5, a small organellar GTPase, in four families with unexplained portal hypertension. We show that GIMAP5 is expressed in hepatic endothelial cells and that its loss in both humans and mice results in capillarization of liver sinusoidal endothelial cells (LSECs); this effect is also seen when GIMAP5 is selectively deleted in endothelial cells. Single-cell RNA-sequencing analysis in a GIMAP5-deficient mouse model reveals replacement of LSECs with capillarized endothelial cells, a reduction of macrovascular hepatic endothelial cells, and places GIMAP5 upstream of GATA4, a transcription factor required for LSEC specification. Thus, GIMAP5 is a critical regulator of liver endothelial cell homeostasis and, when absent, produces portal hypertension. These findings provide new insight into the pathogenesis of portal hypertension, a major contributor to morbidity and mortality from liver disease.
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Registered trials
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.