ArticleFrontiers in immunology2015
Dysfunctional Crohn's Disease-Associated NOD2 Polymorphisms Cannot be Reliably Predicted on the Basis of RIPK2 Binding or Membrane Association.
Article in Frontiers in immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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
9 citing papers in PubMed, 16 citations in OpenAlex.
- Common inherited loss-of-function mutations in the innate sensor NOD2 contribute to exceptional immune response to cancer immunotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Innate Immune Regulation: ABHD17 Is Calling NOD2 Back From Duty.Cellular and molecular gastroenterology and hepatology · 2025Article
- Metabolic regulation of the immune system in health and diseases: mechanisms and interventions.Signal transduction and targeted therapy · 2024Review
- Role and molecular mechanism of NOD2 in chronic non-communicable diseases.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Identifying functional dysregulation of NOD2 variant Q902K in patients with Yao syndrome.Arthritis research & therapy · 2024Article
- NOD2 in Crohn's Disease-Unfinished Business.Journal of Crohn's & colitis · 2023Article
- Valosin-containing protein-regulated endoplasmic reticulum stress causes NOD2-dependent inflammatory responses.Scientific reports · 2022Article
- New Insights and Advances in Pathogenesis and Treatment of Very Early Onset Inflammatory Bowel Disease.Frontiers in pediatrics · 2022Review
- Structural basis of RIP2 activation and signaling.Nature communications · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Polymorphisms in NOD2 represent the single greatest genetic risk factor for the development of Crohn's disease. Three different non-synonomous NOD2 polymorphisms - R702W, G908R, and L1007fsincC - account for roughly 80% of all NOD2-associated cases of Crohn's disease and are reported to result in a loss of receptor function in response to muramyl dipeptide (MDP) stimulation. Loss of NOD2 signaling can result from a failure to detect ligand; alterations in cellular localization; and changes in protein interactions, such as an inability to interact with the downstream adaptor protein RIPK2. Using an overexpression system, we analyzed ~50 NOD2 polymorphisms reportedly connected to Crohn's disease to determine if they also displayed loss of function and if this could be related to alterations in protein localization and/or association with RIPK2. Just under half the polymorphisms displayed a significant reduction in signaling capacity following ligand stimulation, with nine of them showing near complete ablation. Only two polymorphisms, R38M and R138Q, lost the ability to interact with RIPK2. However, both these polymorphisms still associated with cellular membranes. In contrast, L248R, W355stop, L550V, N825K, L1007fsinC, L1007P, and R1019stop still bound RIPK2, but showed impaired membrane association and were unable to signal in response to MDP. This highlights the complex contributions of NOD2 polymorphisms to Crohn's disease and reiterates the importance of both RIPK2 binding and membrane association in NOD2 signaling. Simply ascertaining whether or not NOD2 polymorphisms bind RIPK2 or associate with cellular membranes is not sufficient for determining their signaling competency.
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.