ArticleThe Journal of clinical investigation2020
YIPF5 mutations cause neonatal diabetes and microcephaly through endoplasmic reticulum stress.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Clinical and Molecular Heterogeneity Underlying Monogenic Causes of Pediatric Diabetes Associated to Brain Developmental Disorders.Clinical genetics · 2025Pooled it
- The Hao-Fountain syndrome gene USP7 restricts neurotropic orthoflavivirus entry through cell-intrinsic control of endosomal dynamics.bioRxiv : the preprint server for biology · 2026Article
- Differential immune- and apoptosis-related gene signatures in pancreatic alpha and beta cells contribute to their fate in type 1 diabetes.Cell death and differentiation · 2026Article
- Coordinated expression and assembly of BiP, p58Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Proinsulin regulators identified with CRISPR screen and in vivo mouse QTL mapping.Nature communications · 2026Article
- From bats to humans: uncoveringbioRxiv : the preprint server for biology · 2026Article
- Article
- A new form of diabetes caused by INS mutations defined by zygosity, stem cell and population data.EMBO molecular medicine · 2026Article
- Global perspectives on monogenic forms of diabetes.Diabetologia · 2025Review
- Neonatal diabetes mellitus is a significant feature of COXPD-24 caused by recessive NARS2 variants.Diabetic medicine : a journal of the British Diabetic Association · 2025Article
- Diabetes mellitus and the key role of endoplasmic reticulum stress in pancreatic β cells.Nature reviews. Endocrinology · 2025Review
- Disturbances of endoplasmic reticulum proteostasis in neurodevelopmental disorders.Biochemical Society transactions · 2025Review
- Maturity onset diabetes of the young and beyond: the changing face of single-gene diabetes.European journal of endocrinology · 2025Review
- Article
- Unveiling the molecular mechanisms of recurrent miscarriage through endoplasmic reticulum stress related gene expression.Scientific reports · 2025Article
- Pharmacological and non-pharmacological modulation of endoplasmic reticulum stress in pediatric diabetes.Frontiers in endocrinology · 2025Review
- Exploring proinsulin proteostasis: insights into beta cell health and diabetes.Frontiers in molecular biosciences · 2025Review
- Illness stress-induced transient hyperglycemia in a patient with a novel YIPF5 homozygous missense variant: expanding the phenotype.Hormones (Athens, Greece) · 2024Review
- Neonatal diabetes mellitus around the world: Update 2024.Journal of diabetes investigation · 2024Review
- LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype.Clinical and translational medicine · 2024Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
39 authors at 13 institutions in 9 countries.
Funding
Abstract
Neonatal diabetes is caused by single gene mutations reducing pancreatic β cell number or impairing β cell function. Understanding the genetic basis of rare diabetes subtypes highlights fundamental biological processes in β cells. We identified 6 patients from 5 families with homozygous mutations in the YIPF5 gene, which is involved in trafficking between the endoplasmic reticulum (ER) and the Golgi. All patients had neonatal/early-onset diabetes, severe microcephaly, and epilepsy. YIPF5 is expressed during human brain development, in adult brain and pancreatic islets. We used 3 human β cell models (YIPF5 silencing in EndoC-βH1 cells, YIPF5 knockout and mutation knockin in embryonic stem cells, and patient-derived induced pluripotent stem cells) to investigate the mechanism through which YIPF5 loss of function affects β cells. Loss of YIPF5 function in stem cell-derived islet cells resulted in proinsulin retention in the ER, marked ER stress, and β cell failure. Partial YIPF5 silencing in EndoC-βH1 cells and a patient mutation in stem cells increased the β cell sensitivity to ER stress-induced apoptosis. We report recessive YIPF5 mutations as the genetic cause of a congenital syndrome of microcephaly, epilepsy, and neonatal/early-onset diabetes, highlighting a critical role of YIPF5 in β cells and neurons. We believe this is the first report of mutations disrupting the ER-to-Golgi trafficking, resulting in diabetes.
Indexed as
Identifiers
What OpenQuestion holds
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.