ArticlePLoS genetics2021
TM2D genes regulate Notch signaling and neuronal function in Drosophila.
Article in PLoS genetics, 2021. 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
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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.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Patterns and drivers of 43,617 mosaic chromosomal alterations in blood.Nature genetics · 2026Article
- Prenatal and postnatal effects of gestational immune activation on synaptic and neurodevelopmental pathways via epigenetic mechanisms.Translational psychiatry · 2026Article
- Bi-allelic variants in TM2D3 cause a severe syndromic neurodevelopmental disorder associated with endoplasmic reticulum and mitochondrial abnormalities.American journal of human genetics · 2025Article
- Identification of Protein Biomarkers for DifferentiatingFoods (Basel, Switzerland) · 2024Article
- Towards a Unitary Hypothesis of Alzheimer's Disease Pathogenesis.Journal of Alzheimer's disease : JAD · 2024Article
- Functional unknomics: Systematic screening of conserved genes of unknown function.PLoS biology · 2023Article
- Review
- Functional Studies of Genetic Variants Associated with Human Diseases in Notch Signaling-Related Genes Using Drosophila.Methods in molecular biology (Clifton, N.J.) · 2022Article
- The Rap1 small GTPase affects cell fate or survival and morphogenetic patterning during Drosophila melanogaster eye development.Differentiation; research in biological diversityArticle
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
TM2 domain containing (TM2D) proteins are conserved in metazoans and encoded by three separate genes in each model organism species that has been sequenced. Rare variants in TM2D3 are associated with Alzheimer's disease (AD) and its fly ortholog almondex is required for embryonic Notch signaling. However, the functions of this gene family remain elusive. We knocked-out all three TM2D genes (almondex, CG11103/amaretto, CG10795/biscotti) in Drosophila and found that they share the same maternal-effect neurogenic defect. Triple null animals are not phenotypically worse than single nulls, suggesting these genes function together. Overexpression of the most conserved region of the TM2D proteins acts as a potent inhibitor of Notch signaling at the γ-secretase cleavage step. Lastly, Almondex is detected in the brain and its loss causes shortened lifespan accompanied by progressive motor and electrophysiological defects. The functional links between all three TM2D genes are likely to be evolutionarily conserved, suggesting that this entire gene family may be involved in AD.
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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 Socratic graph.