ArticleBrain research2020
Genome-wide synthetic lethal CRISPR screen identifies FIS1 as a genetic interactor of ALS-linked C9ORF72.
Article in Brain research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 25 citations in OpenAlex.
- Targeting mitochondrial quality control: Ginsenoside Rg1 as a therapeutic candidate for neuromuscular diseases.Journal of ginseng research · 2026Review
- CRISPR-based functional genomic screening in neurodegeneration: mechanistic insights into AD, PD, and ALS.Frontiers in aging neuroscience · 2026Review
- From Cell Architecture to Mitochondrial Signaling: Role of Intermediate Filaments in Health, Aging, and Disease.International journal of molecular sciences · 2025Review
- Poly-GP accumulation due to C9orf72 loss of function induces motor neuron apoptosis through autophagy and mitophagy defects.Autophagy · 2024Article
- A dual sgRNA library design to probe genetic modifiers using genome-wide CRISPRi screens.BMC genomics · 2023Article
- Understanding neural development and diseases using CRISPR screens in human pluripotent stem cell-derived cultures.Frontiers in cell and developmental biology · 2023Review
- Article
- Lysosomal dysfunction in neurodegeneration: emerging concepts and methods.Trends in neurosciences · 2022Review
- Towards application of CRISPR-Cas12a in the design of modern viral DNA detection tools (Review).Journal of nanobiotechnology · 2022Review
- Emerging strategies for the genetic dissection of gene functions, cell types, and neural circuits in the mammalian brain.Molecular psychiatry · 2022Review
- New perspectives on cytoskeletal dysregulation and mitochondrial mislocalization in amyotrophic lateral sclerosis.Translational neurodegeneration · 2021Review
- Fis1 ablation in the male germline disrupts mitochondrial morphology and mitophagy, and arrests spermatid maturation.Development (Cambridge, England) · 2021Article
- Article
- C9ORF72: What It Is, What It Does, and Why It Matters.Frontiers in cellular neuroscience · 2021Review
- Mitochondrial Fission Protein 1: Emerging Roles in Organellar Form and Function in Health and Disease.Frontiers in endocrinology · 2021Review
- CRISPR-based functional genomics for neurological disease.Nature reviews. Neurology · 2020Review
- The Development of C9orf72-Related Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Disorders.Frontiers in genetics · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis (ALS). Both toxic gain of function and loss of function pathogenic mechanisms have been proposed. Accruing evidence from mouse knockout studies point to a role for C9ORF72 as a regulator of immune function. To provide further insight into its cellular function, we performed a genome-wide synthetic lethal CRISPR screen in human myeloid cells lacking C9ORF72. We discovered a strong synthetic lethal genetic interaction between C9ORF72 and FIS1, which encodes a mitochondrial membrane protein involved in mitochondrial fission and mitophagy. Mass spectrometry experiments revealed that in C9ORF72 knockout cells, FIS1 strongly bound to a class of immune regulators that activate the receptor for advanced glycation end (RAGE) products and trigger inflammatory cascades. These findings present a novel genetic interactor for C9ORF72 and suggest a compensatory role for FIS1 in suppressing inflammatory signaling in the absence of C9ORF72.
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.