FOXD3
Identifiers
Aliases	FOXD3, AIS1, Genesis, HFH2, VAMAS2, forkhead box D3
External IDs	OMIM: 611539 MGI: 1347473 HomoloGene: 49239 GeneCards: FOXD3
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p31.3 Start 63,322,567 bp[1] End 63,325,128 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4 C6|4 45.71 cM Start 99,544,536 bp[2] End 99,546,859 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sural nerve spinal ganglia trigeminal ganglion gastric mucosa seminal vesicula left coronary artery transverse colon canal of the cervix fundus vagina Top expressed in neural crest spinal cord urethra ureter salivary gland spinal ganglia enteric nervous system olfactory bulb vasculature tongue More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding DNA-binding transcription repressor activity, RNA polymerase II-specific sequence-specific DNA binding RNA polymerase II transcription regulatory region sequence-specific DNA binding DNA-binding transcription factor activity DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleoplasm nucleus Biological process negative regulation of transcription by RNA polymerase II positive regulation of transcription by RNA polymerase II regulation of transcription, DNA-templated multicellular organism development somatic stem cell population maintenance in utero embryonic development transcription, DNA-templated anatomical structure morphogenesis cell differentiation regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 27022 15221 Ensembl ENSG00000187140 ENSMUSG00000067261 UniProt Q9UJU5 Q61060 RefSeq (mRNA) NM_012183 NM_010425 RefSeq (protein) NP_036315 NP_034555 Location (UCSC) Chr 1: 63.32 – 63.33 Mb Chr 4: 99.54 – 99.55 Mb PubMed search [3] [4]
Wikidata
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Forkhead box D3 also known as FOXD3 is a forkhead protein that in humans is encoded by the FOXD3 gene.^[5]

Function

This gene belongs to the forkhead protein family of transcription factors which is characterized by a DNA-binding forkhead domain. FoxD3 functions as a transcriptional repressor and contains the C-terminal engrailed homology-1 motif (eh1), which provides an interactive surface with a transcriptional co-repressor Grg4 (Groucho-related gene-4).^[6]

Stem Cells

Multiple studies have suggested Foxd3 involvement in the transition from naive to primed pluripotent stem cells in embryo development. Previously, Foxd3 was demonstrated to be required in maintaining pluripotency in mouse embryonic stem cells.^[7] A recent finding further showed that Foxd3 is necessary as a repressor in the transition from ESC to epiblast-like cells (EpiLC).^[8] The study proposed that Foxd3 is associated with inactivation of important naive pluripotency genes by its modification of chromatin structures via recruiting histone demethylases and decreasing the number of activating factors. Another proposed mechanism on the other hand argued that Foxd3 begins nucleosome removal and induction to a "primed" pluripotent state by recruiting Brg1, a nucleosome remodeler, and then acts as a repressor of maximal activation of those enhancers by recruiting histone deacetylases, suggesting a complex mediating function in which enhancers are primed for some future controlled time-point rather than immediate expression.^[9] While there is no ambiguity that Foxd3 plays an important role regulating the transition from naive to primed pluripotency state, the two models show a different process. Attempts to reconcile the conclusions of the two studies have further suggested that Foxd3 functions as all of the above.^[10]

Neural Crest Cells

FOXD3 plays an important role in the development and differentiation of neural crest cells.^[11] Specifically, it is thought that FOXD3 plays an important role in controlling the developmental switch between Schwann Cell Progenitors and Melanocytes.^[11]

Clinical significance

Mutations in this gene cause vitiligo.^[12]