Several GWAS studies have implicated the human gene NFATC1 in kidney dysfunction. NFATC1 encodes a member of the NFAT gene family of transcription co-factors; there are five members of this family in human. There is a single orthologous gene in Drosophila, Dmel\NFAT, for which multiple genetic reagents have been generated, including RNAi targeting constructs, alleles caused by insertional mutagenesis, and an amorphic mutation caused by imprecise excision of a TE insertion.
The human gene Hsap\NFATC1 has been introduced into flies as a component of a chimeric LexA-VP16-NFAT transcription factor tag; it has not been used in the context of this disease model.
Animals homozygous for an amorphic mutation of Dmel\NFAT are viable and fertile with no obvious morphological defects. First instar larvae, but not later larval stages, exhibit significantly increased sensitivity to salt stress (NaCl or KCl in the food).
[updated Feb. 2018 by FlyBase; FBrf0222196]
Reduced estimated glomerular filtration rate (eGFR), a key indicator of renal function; based on a trans-ethnic meta-analysis of nine GWASs comprising 71,638 individuals of diverse ancestries (FBrf0233321).
NFATC1 is associated with kidney dysfunction in multiple GWAS studies (see GWAS Catalog, below in 'External links').
NFAT (Nuclear Factor of Activated T-Cells) proteins are transcription co-factors that play a role in many biological processes. Five NFAT isoforms have been identified to date, NFATC1-C4 and NFAT5. [Gene Cards, NFATC1; 2018.02.23]
Initially discovered in T cells, the NFAT gene family, consisting of five members, regulates immune system, inflammatory response, angiogenesis, cardiac valve formation, myocardial development, axonal guidance, skeletal muscle development, bone homeostasis, development and metastasis of cancer, and many other biological processes (Pan, et al., 2013; pubmed:22950383).
Many to one: 5 human to 1 Drosophila
Moderate-scoring ortholog of NFAT5, NFATC1, NFATC2; 2 additional human genes align over part of the length of the proteins (1 Drosophila to 5 human). Dmel\NFAT shares 23-25% identity and 35-40% similarity with NFAT5, NFATC1 and NFATC2.
