Evidence map›Paper›PMID 41308066›Full record

ArticleNephron2026

Biallelic TMEM72 Variants in Patients with a Nephronophthisis-Like Phenotype.

Laura R Claus, Rozemarijn Snoek, Siebren Faber, Aurelius J C Roskothen-Shevchuk, Elena Sendino Garví, Edith D J Peters, Sanne M C Savelberg, Karen Duran, Bert van der Zwaag, Tri Q Nguyen and 25 more

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Article in Nephron, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

35 authors.

Laura R ClausDepartment of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Rozemarijn SnoekDepartment of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Siebren FaberDepartment of Human Genetics, Radboud UMC, Nijmegen, The Netherlands.
Aurelius J C Roskothen-ShevchukDepartment of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
Elena Sendino GarvíDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Edith D J PetersDepartment of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Sanne M C SavelbergDepartment of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Karen DuranDepartment of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Bert van der ZwaagDepartment of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Tri Q NguyenDepartment of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Roel BroekhuizenDepartment of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Walter J BrummelhuisDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Maarten RookmaakerDepartment of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
Suzanne W van der VeenDepartment of Genetics, Center for Molecular Medicine, Utrecht University, Utrecht, The Netherlands.
Martin G ElferinkDepartment of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Alexandre KarrasDepartment of Nephrology, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Européen Georges Pompidou, Université de Paris, Paris, France.
Laure RaymondSoins Intensifs Néphrologiques et Rein Aigu, Department of Nephrology, Sorbonne Université and Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.
Cyril MousseauxSoins Intensifs Néphrologiques et Rein Aigu, Department of Nephrology, Sorbonne Université and Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.
Omid Sadeghi-AlavijehCentre for Genetics and Genomics, Department of Renal Medicine, University College London, London, UK.
John A SayerBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Eric OlingerBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Ruxandra NeatuBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Verena KlämbtDivision of Pediatric Nephrology, Boston Children's Hospital, Boston, Massachusetts, USA.
Marijn F StokmanDepartment of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Nine V A M KnoersDepartment of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
Federico TessadoriDepartment of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Daniel P GaleCentre for Genetics and Genomics, Department of Renal Medicine, University College London, London, UK.
Karsten BoldtInstitute of Ophthalmic Research, Center for Ophthalmology, University of Tübingen, Tübingen, Germany.
Marius UeffingInstitute of Ophthalmic Research, Center for Ophthalmology, University of Tübingen, Tübingen, Germany.
Gisela G SlaatsDepartment of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
Ronald RoepmanDepartment of Human Genetics, Radboud UMC, Nijmegen, The Netherlands.
Friedhelm HildebrandtNIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne, UK.
Laurent MesnardSoins Intensifs Néphrologiques et Rein Aigu, Department of Nephrology, Sorbonne Université and Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.
Gijs van HaaftenDepartment of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Albertien M van EerdeDepartment of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands, a.vanEerde@umcutrecht.nl.

Funding

NIH HHS R01-DK_068306Wellcome Trust
6 · The paper itself

Abstract

introductionNephronophthisis (NPHP) is an autosomal recessive kidney disease resulting mainly from primary cilium defects, with unspecific and variable symptoms that can progress to kidney failure needing replacement therapy at a young age. Currently, up to 64% of likely NPHP cases can be diagnosed by assessing known genes. Therefore, there is a need to gain more insight in what genes can cause this disease.

methodsIn a diagnostic setting, we performed broad genetic testing in patients with advanced kidney disease. We carried out in silico and in vitro analyses for TMEM72, including immunohistochemistry and affinity proteomics, and in vivo experiments to further interpret our findings.

resultsWe identified biallelic TMEM72 variants in 9 patients from six families with a phenotype suggestive for NPHP. Five families presented with kidney failure at a (young) adult age. One family had a different phenotype with prenatal onset of kidney failure and neurological symptoms. The phenotypes of the patients correspond to TMEM72 expression mainly in the kidney. In silico analyses indicate that homozygous loss-of-function variants are likely not tolerated in TMEM72. Immunohistochemistry staining of kidney biopsies revealed altered localization and expression of TMEM72 in cases compared to controls. In human-derived tubuloids, we showed that TMEM72 localizes to the cilium. Furthermore, using an affinity proteomics approach, we found an association of TMEM72 and ciliary function, more specifically in selective ciliary cholesterol transport.

conclusionWe present the first genetic evidence, underlined by immunohistochemistry and protein binding assays, linking TMEM72 variants to kidney disease and ciliary function. We conclude that TMEM72 is a candidate gene for NPHP. Future work is needed to further characterize TMEM72 variants and unravel its disease mechanism.

Indexed as

Kidney Diseases, CysticMembrane ProteinsAdolescentAdultChildCiliaFemaleHumansMaleMiddle AgedPedigreePhenotypeYoung AdultMembrane ProteinsCiliopathyKidney failure needing replacement therapyMonogenic kidney diseaseNephronophthisisTMEM72

Identifiers

PMID41308066
PMCPMC12782617

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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.