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. 2021 Mar 8;22(5):2725. doi: 10.3390/ijms22052725

Table 1.

Functions and diseases associated with NFAT family members.

Isoform

  1. Regulation

  2. Intracellular Localization

 Involvement in Organ/Tissue Formation or Cell Function Abnormal NFAT Activity
Human Knockout Mouse
NFATc1

  1. Calcineurin

  2. Cytoplasm (in resting cells) Nucleus (in activated cells)

 Heart valve/septum formation [5,17], angiogenesis [32,33], osteoclast formation [28], T cell proliferation/Th2 differentiation [82,83] Pancreatic cancer [31], colon cancer (increased risk of metastasis) [36], leukemia [35,37], lymphoma [39] Embryonic lethality (circulatory failure) [5]
NFATc2 Cell cycle arrest/cell growth inhibition (normal cells) [26,41], activation-induced cell death [59], regulation of angiogenesis [45] Pancreatic cancer [44], lung adenocarcinoma (> stage II) [43], mild cognitive impairment [50] Increased immune reactivity [21,22], allergic contact hypersensitivity [59], lymphoma [42], lymphocyte hyperplasia (NFATc2/c3 DKO) [53],
NFATc3 - Lung squamous cell carcinoma (well-differentiated cancer) [43], glioma [46] lymphocyte hyperplasia (NFATc2/c3 DKO) [53], embryonic lethality (vascular hypoplasia, NFATc3/c4 DKO) [18]
NFATc4 Nervous system assembly/spatial memory formation
[6,23]		 Skin cancer [47], severe cognitive impairment [50], Alzheimer’s disease [50] Spatial memory dysplasia [23], embryonic lethality (vascular hypoplasia, NFATc3/c4 DKO) [18]
NFAT5

  1. mainly osmotic pressure

  2. cytoplasm and nucleus

 Cell protection under hypertonic stress [8], homeostasis [9] Rheumatoid arthritis [63] Mostly embryonic lethality (decreased cardiac function, renal atrophy) [19,20]

DKO: double knock-out.