ArticleHuman molecular genetics2016
Cystic fibrosis gene modifier SLC26A9 modulates airway response to CFTR-directed therapeutics.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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.
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.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 90 citations in OpenAlex.
- Impact of Gene Modifiers on Cystic Fibrosis Phenotypic Profiles: A Systematic Review.Human mutation · 2024Pooled it
- New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries.Nature genetics · 2019Pooled it
- Nucleotide Variant in theJournal of clinical medicine · 2026Article
- Distinct regulatory elements of SLC6A14 expression contribute to modification of cystic fibrosis phenotypes.Human genetics · 2026Article
- Lack of SLC26A9-mediated chloride secretion causes mucus plugging and severe respiratory distress in neonatal mice.JCI insight · 2025Article
- Single-cell RNA-sequencing co-expression analysis with CFTR and CF modifier genes in lung tissue.Scientific reports · 2025Article
- The role of the STAS domain in SLC26A9 for chloride ion transporter function.Biophysical journal · 2024Article
- Convergent gene losses and pseudogenizations in multiple lineages of stomachless fishes.Communications biology · 2024Article
- SLC26 Anion Transporters.Handbook of experimental pharmacology · 2024Review
- SLC26A9 in airways and intestine: secretion or absorption?Channels (Austin, Tex.) · 2023Review
- Pathogenic Relationships in Cystic Fibrosis and Renal Diseases: CFTR, SLC26A9 and Anoctamins.International journal of molecular sciences · 2023Review
- Modifier Factors of Cystic Fibrosis Phenotypes: A Focus on Modifier Genes.International journal of molecular sciences · 2022Review
- Genetic evidence supports the development of SLC26A9 targeting therapies for the treatment of lung disease.NPJ genomic medicine · 2022Article
- Expression of SLC26A9 in Airways and Its Potential Role in Asthma.International journal of molecular sciences · 2022Article
- Factors Predisposing the Response to Lumacaftor/Ivacaftor in People with Cystic Fibrosis.Journal of personalized medicine · 2022Article
- SLC26A9 as a Potential Modifier and Therapeutic Target in Cystic Fibrosis Lung Disease.Biomolecules · 2022Review
- SLC26A9 is selected for endoplasmic reticulum associated degradation (ERAD) via Hsp70-dependent targeting of the soluble STAS domain.The Biochemical journal · 2021Article
- Genetic Modifying Factors of Cystic Fibrosis Phenotype: A Challenge for Modern Medicine.Journal of clinical medicine · 2021Review
- Synergy in Cystic Fibrosis Therapies: Targeting SLC26A9.International journal of molecular sciences · 2021Article
- Separating the contributions of SLC26A9 and CFTR to anion secretion in primary human bronchial epithelia.American journal of physiology. Lung cellular and molecular physiology · 2021Article
Corrections and comments
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Authors and funding
22 authors at 9 institutions in 2 countries.
Funding
Abstract
Cystic fibrosis is realizing the promise of personalized medicine. Recent advances in drug development that target the causal CFTR directly result in lung function improvement, but variability in response is demanding better prediction of outcomes to improve management decisions. The genetic modifier SLC26A9 contributes to disease severity in the CF pancreas and intestine at birth and here we assess its relationship with disease severity and therapeutic response in the airways. SLC26A9 association with lung disease was assessed in individuals from the Canadian and French CF Gene Modifier consortia with CFTR-gating mutations and in those homozygous for the common Phe508del mutation. Variability in response to a CFTR-directed therapy attributed to SLC26A9 genotype was assessed in Canadian patients with gating mutations. A primary airway model system determined if SLC26A9 shows modification of Phe508del CFTR function upon treatment with a CFTR corrector. In those with gating mutations that retain cell surface-localized CFTR we show that SLC26A9 modifies lung function while this is not the case in individuals homozygous for Phe508del where cell surface expression is lacking. Treatment response to ivacaftor, which aims to improve CFTR-channel opening probability in patients with gating mutations, shows substantial variability in response, 28% of which can be explained by rs7512462 in SLC26A9 (P = 0.0006). When homozygous Phe508del primary bronchial cells are treated to restore surface CFTR, SLC26A9 likewise modifies treatment response (P = 0.02). Our findings indicate that SLC26A9 airway modification requires CFTR at the cell surface, and that a common variant in SLC26A9 may predict response to CFTR-directed therapeutics.
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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 OpenQuestion graph.