ArticleAmerican journal of human genetics2015
Loss-of-Function Mutations in APPL1 in Familial Diabetes Mellitus.
Article in American journal of human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 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
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Treatment Options for Patients with Maturity-Onset Diabetes of the Young (MODY): A Systematic Review of Literature: 2026 Update.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026Pooled it
- Residual β cell function and monogenic variants in long-duration type 1 diabetes patients.The Journal of clinical investigation · 2019Trial
- Exome Sequencing in Patients with Loin Pain Hematuria Syndrome and Persistent Isolated Hematuria.Kidney international reports · 2026Article
- Genetic spectrum and treatment implications of maturity-onset diabetes of the young in the eastern Black Sea region of Türkiye: a combined adult and pediatric cohort of 296 patients with identification of rare and novel variants.Molecular biology reports · 2026Article
- Maturity onset diabetes of the young and beyond: the changing face of single-gene diabetes.European journal of endocrinology · 2025Review
- Zebrafish as a preclinical model for diabetes mellitus and its complications: From monogenic to gestational diabetes and beyond.World journal of diabetes · 2025Review
- Decoding MODY: exploring genetic roots and clinical pathways.Diabetology international · 2025Review
- [Striking manifestation and unexpected therapeutic course of diabetes mellitus in a 22-year-old male patient].Innere Medizin (Heidelberg, Germany) · 2025Article
- Exploring histone deacetylases in type 2 diabetes mellitus: pathophysiological insights and therapeutic avenues.Clinical epigenetics · 2024Review
- Screening of Mutations in Maturity-onset Diabetes of the Young-related Genes andJournal of clinical research in pediatric endocrinology · 2024Article
- A synonymousMolecular genetics and metabolism reports · 2024Article
- Assessment of pathogenicity and functional characterization ofWorld journal of diabetes · 2024Article
- Modelling human diabetesFrontiers in endocrinology · 2024Review
- Whole-exome sequencing in familial type 2 diabetes identifies an atypical missense variant in the RyR2 gene.Frontiers in endocrinology · 2024Article
- Identification of osteoporosis genes using family studies.Frontiers in endocrinology · 2024Review
- Monogenic diabetes.Nature reviews. Disease primers · 2023Review
- Whole-genome sequencing of multiple related individuals with type 2 diabetes reveals an atypical likely pathogenic mutation in the PAX6 gene.European journal of human genetics : EJHG · 2023Article
- Statistical evidence for high-penetrance MODY-causing genes in a large population-based cohort.Endocrinology, diabetes & metabolism · 2022Article
- Insights into the Genetics and Signaling Pathways in Maturity-Onset Diabetes of the Young.International journal of molecular sciences · 2022Review
- Maturity-Onset Diabetes of the Young: Mutations, Physiological Consequences, and Treatment Options.Journal of personalized medicine · 2022Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 5 institutions in 2 countries.
Funding
Abstract
Diabetes mellitus is a highly heterogeneous disorder encompassing several distinct forms with different clinical manifestations including a wide spectrum of age at onset. Despite many advances, the causal genetic defect remains unknown for many subtypes of the disease, including some of those forms with an apparent Mendelian mode of inheritance. Here we report two loss-of-function mutations (c.1655T>A [p.Leu552(∗)] and c.280G>A [p.Asp94Asn]) in the gene for the Adaptor Protein, Phosphotyrosine Interaction, PH domain, and leucine zipper containing 1 (APPL1) that were identified by means of whole-exome sequencing in two large families with a high prevalence of diabetes not due to mutations in known genes involved in maturity onset diabetes of the young (MODY). APPL1 binds to AKT2, a key molecule in the insulin signaling pathway, thereby enhancing insulin-induced AKT2 activation and downstream signaling leading to insulin action and secretion. Both mutations cause APPL1 loss of function. The p.Leu552(∗) alteration totally abolishes APPL1 protein expression in HepG2 transfected cells and the p.Asp94Asn alteration causes significant reduction in the enhancement of the insulin-stimulated AKT2 and GSK3β phosphorylation that is observed after wild-type APPL1 transfection. These findings-linking APPL1 mutations to familial forms of diabetes-reaffirm the critical role of APPL1 in glucose homeostasis.
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.