The present invention is related to a method for diagnosing cystic fibrosis in a subject comprising a step a), wherein the step a) comprises detecting a biomarker in a sample from the subject, wherein the sample is a sample selected from the group comprising blood, a blood product, urine, saliva, cerebrospinal liquid, stool, tissue and lymph liquid.

The present invention provides novel mutations identified in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that can be used for a more accurate diagnosis of cystic fibrosis (CF) and CF related disorders. Methods for testing a sample obtained from a subject to determine the presence of one or more mutations in the CFTR gene are provided wherein the presence of one or more mutations indicates that the subject has CF or a CF related disorder, or is a carrier of a CFTR mutation.

Provided herein are methods and systems for screening a candidate agent to determine whether the candidate agent modulates an activity of cultured cells. Compositions for screening a candidate agent are also provided herein.

A corrector agent capable of stabilizing a newly synthesized cystic fibrosis transmembrane conductance regulator (CFTR) protein, useful in the treatment of cystic fibrosis.

The present disclosure is based, in part, on the discovery that disclosed compounds such as those having Formula (IVa), (Va), (IV), or (V) can increase cystic fibrosis transmembrane conductance regulator (CFTR) activity as measured in human bronchial epithelial (hBE) cells.

Disclosed herein are methods for detecting protein expression in an individual diagnosed with cystic fibrosis. The methods, in certain aspects, include the steps of obtaining a sample from said individual and detecting expression in said sample of each protein of a protein set. The method may further include the step of determining expression level of one or more proteins of the protein set. The disclosed methods may be used to predict one or more clinical parameters in an individual having cystic fibrosis.

The present disclosure provides, inter alia, a recombinant engineered deubiquitinase (DUB) and methods for treating or ameliorating an inherited ion channelopathy, such as long QT syndrome, Brugada syndrome, or cystic fibrosis, in a subject. Further provided are methods for screening mutations causing such inherited ion channelopathies for a trafficking-deficient mutation that is treatable by the recombinant engineered DUB disclosed herein.

The present disclosure provides, inter alia, a recombinant engineered deubiquitinase (DUB) and methods for treating or ameliorating an inherited ion channelopathy, such as long QT syndrome, Brugada syndrome, or cystic fibrosis, in a subject. Further provided are methods for screening mutations causing such inherited ion channelopathies for a trafficking-deficient mutation that is treatable by the recombinant engineered DUB disclosed herein.

Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (ABC) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

The present invention provides novel mutations of the CFTR gene related to cystic fibrosis or to conditions associated with cystic fibrosis. Also provided are probes for detecting the mutant sequences. Methods of identifying if an individual has a genotype containing one or more mutations in the CFTR gene are further provided.