PMC:4156421 / 18368-19876 JSONTXT

{"project":"2_test","denotations":[{"id":"25192356-23783374-90446775","span":{"begin":695,"end":697},"obj":"23783374"},{"id":"25192356-23783374-90446776","span":{"begin":1128,"end":1130},"obj":"23783374"}],"text":"Rare coding variants\nTo assess genes not previously associated with IPF but potentially relevant to observed pathology, we filtered variants for rare protein-altering SNVs. With a MAF threshold of 0.01, we identified 1,291 novel or rare coding SNVs. A subset of 57 coding variants at nucleotide positions demonstrating significant interspecies conservation (conScoreGERP \u003e5.75) were delineated (Table S3). GeneCards (http://genecards.org) and literature searches were consulted to determine the function, associated disease, and expression profile of each of these variants. Few of these variants are known to be expressed in lung or specifically in diseased lung tissue from patients with IPF [28]; however, this does not rule out their contribution to disease as the expression profile may be incomplete, the gene's effect on the lung may be indirectly mediated through exogenous inflammatory pathways, or the deleterious effects of the genes may arise from abnormal expression. We compared our list of novel variants to a previously published set of genes that are differentially expressed between IPF patients and controls [28]. Twenty-nine/146 of the novel variants are included in this set. Three are nonsense variants: NCKAP5 and SLC25A25, which were underexpressed in IPF patients, and MNS1/TEX9, which was overexpressed in IPF patients. Other coding variants for genes in this list have previously been associated with different inherited disorders, but none seem pertinent to the patient's illness."}