======= SIX4 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: SIX4
  * **<color #00a2e8>Official Name</color>**: SIX homeobox 4
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=51804|51804]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q9UIU6|Q9UIU6]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=SIX4&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20SIX4|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/606342|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a member of the homeobox family, subfamily SIX. The drosophila homolog is a nuclear homeoprotein required for eye development. Studies in mouse show that this gene product functions as a transcription factor, and may have a role in the differentiation or maturation of neuronal cells. [provided by RefSeq, May 2010]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Transcriptional regulator which can act as both a transcriptional repressor and activator by binding a DNA sequence on these target genes and is involved in processes like cell differentiation, cell migration and cell survival. Transactivates gene expression by binding a 5'-[CAT]A[CT][CT][CTG]GA[GAT]-3' motif present in the Trex site and a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 site of the muscle-specific genes enhancer. Acts cooperatively with EYA proteins to transactivate their target genes through interaction and nuclear translocation of EYA protein. Acts synergistically with SIX1 to regulate target genes involved in formation of various organs, including muscle, kidney, gonad, ganglia, olfactory epithelium and cranial skeleton. Plays a role in several important steps of muscle development. Controls the genesis of hypaxial myogenic progenitors in the dermomyotome by transactivating PAX3 and the delamination and migration of the hypaxial precursors from the ventral lip to the limb buds through the transactivation of PAX3, MET and LBX1. Controls myoblast determination by transactivating MYF5, MYOD1 and MYF6. Controls somitic differentiation in myocyte through MYOG transactivation. Plays a role in synaptogenesis and sarcomere organization by participating in myofiber specialization during embryogenesis by activating fast muscle program in the primary myotome resulting in an up-regulation of fast muscle genes, including ATP2A1, MYL1 and TNNT3. Simultaneously, is also able to activate inhibitors of slow muscle genes, such as SOX6, HRASLS, and HDAC4, thereby restricting the activation of the slow muscle genes. During muscle regeneration, negatively regulates differentiation of muscle satellite cells through down-regulation of MYOG expression. During kidney development regulates the early stages of metanephros development and ureteric bud formation through regulation of GDNF, SALL1, PAX8 and PAX2 expression. Plays a role in gonad development by regulating both testis determination and size determination. In gonadal sex determination, transactivates ZFPM2 by binding a MEF3 consensus sequence, resulting in SRY up-regulation. In gonadal size determination, transactivates NR5A1 by binding a MEF3 consensus sequence resulting in gonadal precursor cell formation regulation. During olfactory development mediates the specification and patterning of olfactory placode through fibroblast growth factor and BMP4 signaling pathways and also regulates epithelial cell proliferation during placode formation. Promotes survival of sensory neurons during early trigeminal gangliogenesis. In the developing dorsal root ganglia, up- regulates SLC12A2 transcription. Regulates early thymus/parathyroid organogenesis through regulation of GCM2 and FOXN1 expression. Forms gustatory papillae during development of the tongue. Also plays a role during embryonic cranial skeleton morphogenesis. {ECO:0000250|UniProtKB:Q61321}.

<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'>
|skeletal muscle fiber differentiation|
|olfactory placode development|
|olfactory placode formation|
|olfactory placode morphogenesis|
|myotome development|
|regulation of branch elongation involved in ureteric bud branching|
|positive regulation of ureteric bud formation|
|negative regulation of satellite cell differentiation|
|positive regulation of epithelial tube formation|
|regulation of ureteric bud formation|
|trigeminal ganglion development|
|fungiform papilla morphogenesis|
|regulation of synaptic growth at neuromuscular junction|
|fungiform papilla development|
|negative regulation of skeletal muscle cell differentiation|
|cranial ganglion development|
|tongue morphogenesis|
|ectodermal placode morphogenesis|
|ectodermal placode formation|
|regulation of neuromuscular junction development|
|ectodermal placode development|
|negative regulation of skeletal muscle tissue development|
|myoblast migration|
|metanephric mesenchyme development|
|male sex determination|
|nose development|
|ganglion development|
|kidney mesenchyme development|
|positive regulation of branching involved in ureteric bud morphogenesis|
|regulation of epithelial tube formation|
|regulation of skeletal muscle cell differentiation|
|tongue development|
|positive regulation of mesonephros development|
|regulation of branching involved in ureteric bud morphogenesis|
|muscle cell migration|
|sex determination|
|regulation of mesonephros development|
|pharyngeal system development|
|positive regulation of morphogenesis of an epithelium|
|positive regulation of embryonic development|
|positive regulation of kidney development|
|thymus development|
|embryonic cranial skeleton morphogenesis|
|sarcomere organization|
|negative regulation of striated muscle tissue development|
|regulation of skeletal muscle tissue development|
|negative regulation of muscle organ development|
|skeletal muscle cell differentiation|
|cranial nerve development|
|negative regulation of muscle tissue development|
|regulation of kidney development|
|regulation of morphogenesis of a branching structure|
|myotube differentiation|
|myofibril assembly|
|cranial skeletal system development|
|transcription regulatory region sequence-specific DNA binding|
|nerve development|
|positive regulation of animal organ morphogenesis|
|somite development|
|metanephros development|
|embryonic skeletal system morphogenesis|
|inner ear morphogenesis|
|cellular component assembly involved in morphogenesis|
|regulation of synapse assembly|
|actomyosin structure organization|
|ear morphogenesis|
|skeletal muscle tissue development|
|embryonic skeletal system development|
|regulation of embryonic development|
|regulation of striated muscle tissue development|
|skeletal muscle organ development|
|male gonad development|
|regulation of muscle tissue development|
|striated muscle cell development|
|development of primary male sexual characteristics|
|regulation of muscle organ development|
|negative regulation of neuron apoptotic process|
|muscle cell development|
|male sex differentiation|
|protein localization to nucleus|
|regulation of morphogenesis of an epithelium|
|inner ear development|
|respiratory system development|
|striated muscle cell differentiation|
|transcription factor complex|
|negative regulation of neuron death|
|regulation of neuron apoptotic process|
|gonad development|
|development of primary sexual characteristics|
|regulation of synapse organization|
|ear development|
|mesenchyme development|
|regulation of synapse structure or activity|
|skeletal system morphogenesis|
|muscle cell differentiation|
|sensory organ morphogenesis|
|regulation of animal organ morphogenesis|
|sex differentiation|
|kidney development|
|renal system development|
|striated muscle tissue development|
|embryonic organ morphogenesis|
|muscle organ development|
|muscle tissue development|
|regulation of neuron death|
|urogenital system development|
|regulation of developmental growth|
|regulation of epithelial cell proliferation|
|gland development|
|reproductive structure development|
|reproductive system development|
|embryonic organ development|
|DNA-binding transcription activator activity, RNA polymerase II-specific|
|supramolecular fiber organization|
|muscle structure development|
|skeletal system development|
|actin cytoskeleton organization|
|RNA polymerase II proximal promoter sequence-specific DNA binding|
|sensory organ development|
|embryonic morphogenesis|
|actin filament-based process|
|hematopoietic or lymphoid organ development|
|chordate embryonic development|
|immune system development|
|embryo development ending in birth or egg hatching|
|developmental process involved in reproduction|
|regulation of growth|
|negative regulation of cell differentiation|
|protein localization to organelle|
|organelle assembly|
|cellular component morphogenesis|
|negative regulation of apoptotic process|
|anatomical structure formation involved in morphogenesis|
|negative regulation of programmed cell death|
|regulation of nervous system development|
|negative regulation of developmental process|
|animal organ morphogenesis|
|regulation of cellular component biogenesis|
|cell migration|
|embryo development|
|negative regulation of cell death|
|regulation of protein localization|
|regulation of anatomical structure morphogenesis|
|localization of cell|
|cell motility|
|cytoskeleton organization|
|epithelium development|
|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|
|locomotion|
|negative regulation of RNA metabolic process|
|positive regulation of developmental process|
|negative regulation of cellular macromolecule biosynthetic process|
|reproductive process|
|reproduction|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|negative regulation of cellular biosynthetic process|
|generation of neurons|
|positive regulation of transcription, DNA-templated|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|movement of cell or subcellular component|
|DNA-binding transcription factor activity, RNA polymerase II-specific|
|regulation of programmed cell death|
|cellular protein localization|
|cellular macromolecule localization|
|regulation of cell population proliferation|
|neurogenesis|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|cell development|
|regulation of cell death|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|tissue development|
|regulation of cell differentiation|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic 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:exp291|LLY-284 2.6μM R06 exp291]]|-1.88|
|[[:results:exp475|CyclicAMP 200μM R08 exp475]]|1.9|
</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>**: 6803
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 1.31 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='SIX4 Expression in NALM6 Cells: 1.31'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>