Table 2

The various domains of the FOXP3 protein, and the predicted functional impact of mutations on FOXP3 regulatory function

Sequence	Affected molecular domains	Expected mechanistic dysfunctions	Expected functional consequence
1–69	Repressor domain	Partial loss of transcriptional repression	Activation-induced inflammatory cytokine production by Treg
70–105	NFAT:AP1 repression	Partial loss of transcriptional repression	Activation-induced inflammatory cytokine production by Treg
	RORα binding	Loss of Th17 control	Overzealous Th17 responses
	Lysine acetylation	Deregulated subcellular localisation	Deficient transcriptional regulation.
106–132	NFAT:AP1 repression	Loss of transcriptional repression	Activation-induced inflammatory cytokine production by Treg
106–132	Association with HDAC	Impaired access to chromatin	Deficient transcriptional regulation
133–190	Association with HDAC	Impaired access to chromatin	Deficient transcriptional regulation
200–223	Zinc finger domain	NA	NA
240–261	Leucine zipper domain	Loss of FOXP3 oligomerisation	Deficient transcriptional regulation
240–261	Leucine zipper domain	Partial loss of DNA binding and HDAC association	Deficient transcriptional regulation
261–337	LZ-FKH loop	Binding to RUNX1	Activation-induced inflammatory cytokine production by Treg
337–421	DNA binding	Impaired binding to DNA	Deficient transcriptional regulation
	NFAT/AP1 repression	Loss of transcriptional repression	Activation-induced inflammatory cytokine production by Treg
	Swap dimer formation	Unstable FOXP3 dimers	Deficient transcriptional regulation