======= SIX3 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: SIX3
  * **<color #00a2e8>Official Name</color>**: SIX homeobox 3
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=6496|6496]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O95343|O95343]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=SIX3&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20SIX3|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/603714|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a member of the sine oculis homeobox transcription factor family. The encoded protein plays a role in eye development. Mutations in this gene have been associated with holoprosencephaly type 2. [provided by RefSeq, Oct 2009]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Transcriptional regulator which can act as both a transcriptional repressor and activator by binding a ATTA homeodomain core recognition sequence on these target genes. During forebrain development represses WNT1 expression allowing zona limitans intrathalamica formation and thereby ensuring proper anterio-posterior patterning of the diencephalon and formation of the rostral diencephalon. Acts as a direct upstream activator of SHH expression in the rostral diencephalon ventral midline and that in turn SHH maintains its expression. In addition, Six3 activity is required for the formation of the telencephalon. During postnatal stages of brain development is necessary for ependymal cell maturation by promoting the maturation of radial glia into ependymal cells through regulation of neuroblast proliferation and migration. Acts on the proliferation and differentiation of neural progenitor cells through activating transcription of CCND1 AND CCND2. During early lens formation plays a role in lens induction and specification by activating directly PAX6 in the presumptive lens ectoderm. In turn PAX6 activates SIX3 resulting in activation of PDGFRA and CCND1 promoting cell proliferation. Also is required for the neuroretina development by directly suppressing WNT8B expression in the anterior neural plate territory. Its action during retina development and lens morphogenesis is AES and TLE4-dependent manner. Furthermore, during eye development regulates several genes expression. Before and during early lens development represses the CRYGF promoter by binding a SIX repressor element. Directly activates RHO transcription, or cooperates with CRX or NRL. Six3 functions also in the formation of the proximodistal axis of the optic cup, and promotes the formation of optic vesicles-like structures. During pituitary development, acts in parallel or alternatively with HESX1 to control cell proliferation through Wnt/beta-catenin pathway (By similarity). Plays a role in eye development by suppressing WNT1 expression and in dorsal- ventral patterning by repressing BMP signaling pathway. {ECO:0000250|UniProtKB:Q62233, ECO:0000269|PubMed:18791198}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Homeobox|
|Homeobox KN|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|optic vesicle morphogenesis|
|neuroblast migration|
|proximal/distal axis specification|
|lens fiber cell apoptotic process|
|forebrain anterior/posterior pattern specification|
|neuroblast differentiation|
|lens induction in camera-type eye|
|regulation of neural retina development|
|regulation of retina development in camera-type eye|
|forebrain dorsal/ventral pattern formation|
|telencephalon regionalization|
|transcription corepressor binding|
|epithelial cell maturation|
|lens morphogenesis in camera-type eye|
|circadian behavior|
|rhythmic behavior|
|forebrain regionalization|
|embryonic camera-type eye morphogenesis|
|developmental induction|
|lens fiber cell differentiation|
|apoptotic process involved in development|
|epithelial cell apoptotic process|
|cell proliferation in forebrain|
|proximal/distal pattern formation|
|regulation of neuroblast proliferation|
|embryonic eye morphogenesis|
|embryonic camera-type eye development|
|pituitary gland development|
|regulation of stem cell proliferation|
|neural precursor cell proliferation|
|diencephalon development|
|transcription regulatory region sequence-specific DNA binding|
|lens development in camera-type eye|
|dorsal/ventral pattern formation|
|axis specification|
|regulation of neural precursor cell proliferation|
|protein import into nucleus|
|RNA polymerase II distal enhancer sequence-specific DNA binding|
|histone deacetylase binding|
|camera-type eye morphogenesis|
|import into nucleus|
|endocrine system development|
|anatomical structure maturation|
|protein import|
|circadian rhythm|
|eye morphogenesis|
|cell maturation|
|stem cell differentiation|
|protein localization to nucleus|
|epithelial cell development|
|transcription factor complex|
|negative regulation of Wnt signaling pathway|
|anterior/posterior pattern specification|
|visual perception|
|sensory perception of light stimulus|
|negative regulation of neuron differentiation|
|developmental maturation|
|sensory organ morphogenesis|
|telencephalon development|
|nucleocytoplasmic transport|
|nuclear transport|
|rhythmic process|
|transcription coactivator activity|
|embryonic organ morphogenesis|
|negative regulation of neurogenesis|
|negative regulation of nervous system development|
|camera-type eye development|
|regionalization|
|negative regulation of cell development|
|signaling receptor binding|
|eye development|
|visual system development|
|regulation of Wnt signaling pathway|
|sensory system development|
|forebrain development|
|gland development|
|establishment of protein localization to organelle|
|embryonic organ development|
|pattern specification process|
|DNA-binding transcription activator activity, RNA polymerase II-specific|
|regulation of cell cycle phase transition|
|sensory organ development|
|cell population proliferation|
|tissue morphogenesis|
|embryonic morphogenesis|
|behavior|
|regulation of neuron differentiation|
|DNA-binding transcription factor activity|
|epithelial cell differentiation|
|negative regulation of cell differentiation|
|protein localization to organelle|
|brain development|
|regulation of cell cycle process|
|head development|
|regulation of neurogenesis|
|apoptotic process|
|regulation of nervous system development|
|regulation of cell development|
|negative regulation of developmental process|
|animal organ morphogenesis|
|cell migration|
|sensory perception|
|embryo development|
|central nervous system development|
|intracellular protein transport|
|programmed cell death|
|cell motility|
|localization of cell|
|cell death|
|epithelium development|
|regulation of cell cycle|
|negative regulation of transcription, DNA-templated|
|negative regulation of multicellular organismal process|
|positive regulation of transcription by RNA polymerase II|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|negative regulation of signal transduction|
|locomotion|
|negative regulation of RNA metabolic process|
|negative regulation of cell communication|
|negative regulation of signaling|
|nervous system process|
|negative regulation of cellular macromolecule biosynthetic process|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|protein transport|
|negative regulation of cellular biosynthetic process|
|intracellular transport|
|generation of neurons|
|peptide transport|
|positive regulation of transcription, DNA-templated|
|negative regulation of biosynthetic process|
|movement of cell or subcellular component|
|DNA-binding transcription factor activity, RNA polymerase II-specific|
|amide transport|
|cellular protein localization|
|cellular macromolecule localization|
|establishment of protein localization|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|neurogenesis|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|cell development|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|tissue development|
|regulation of cell differentiation|
|establishment of localization in cell|
|nitrogen compound transport|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|system process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp148|SB202190 10μM R03 exp148]]|-1.78|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 12100
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: -0.55 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='SIX3 Expression in NALM6 Cells: -0.55'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>