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Aliases for SIX3 Gene

Aliases for SIX3 Gene

  • SIX Homeobox 3 2 3 5
  • Sine Oculis Homeobox Homolog 3 3 4
  • Sine Oculis Homeobox Homolog 3 (Drosophila) 2
  • Holoprosencephaly 2, Alobar Or Semilobar 2
  • Sine Oculis Homeobox-Like Protein 3 3
  • Homeobox Protein SIX3 3
  • HPE2 3

External Ids for SIX3 Gene

Previous HGNC Symbols for SIX3 Gene

  • HPE2

Previous GeneCards Identifiers for SIX3 Gene

  • GC02P045167
  • GC02P045337
  • GC02P045143
  • GC02P045080
  • GC02P045022
  • GC02P044885
  • GC02P045168

Summaries for SIX3 Gene

Entrez Gene Summary for SIX3 Gene

  • 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]

GeneCards Summary for SIX3 Gene

SIX3 (SIX Homeobox 3) is a Protein Coding gene. Diseases associated with SIX3 include Schizencephaly and Holoprosencephaly-2. Among its related pathways are Circadian rythm related genes and Preimplantation Embryo. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and transcription coactivator activity. An important paralog of this gene is SIX6.

UniProtKB/Swiss-Prot for SIX3 Gene

  • 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.

Gene Wiki entry for SIX3 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SIX3 Gene

Genomics for SIX3 Gene

Regulatory Elements for SIX3 Gene

Enhancers for SIX3 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH02G044936 0.9 FANTOM5 ENCODE 19.2 -7.6 -7594 0.4 CBX8 RNF2 SUZ12 CBX2 CTBP2 ZNF398 EZH2 SIX3 ENSG00000276229 ENSG00000277311
GH02G044932 0.5 FANTOM5 9.3 -8.7 -8683 0.1 SUZ12 CBX2 EZH2 SIX3 ENSG00000277311 ENSG00000274520
GH02G044933 0.6 FANTOM5 3.9 -8.0 -8027 0.2 CBX8 RNF2 SUZ12 CBX2 EZH2 SIX3 ENSG00000277311 ENSG00000274520
GH02G044836 0.6 FANTOM5 2.3 -105.5 -105475 0.5 EED JUNB FOS RELA SIX3 GC02P044838 LOC105374573
GH02G044837 0.3 FANTOM5 2.1 -104.2 -104210 0.4 SIX3 GC02P044838 LOC105374573
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around SIX3 on UCSC Golden Path with GeneCards custom track

Genomic Location for SIX3 Gene

Chromosome:
2
Start:
44,941,729 bp from pter
End:
44,966,751 bp from pter
Size:
25,023 bases
Orientation:
Plus strand

Genomic View for SIX3 Gene

Genes around SIX3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SIX3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SIX3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SIX3 Gene

Proteins for SIX3 Gene

  • Protein details for SIX3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95343-SIX3_HUMAN
    Recommended name:
    Homeobox protein SIX3
    Protein Accession:
    O95343
    Secondary Accessions:
    • D6W5A5
    • Q53T42

    Protein attributes for SIX3 Gene

    Size:
    332 amino acids
    Molecular mass:
    35487 Da
    Quaternary structure:
    • Interacts with EYA4; translocates EYA4 from the cytoplasm to the nucleus and promotes activation of their target genes (By similarity). Interacts with MTA1 and HDAC2; represses its own transcription (By similarity). Interacts with MTA1; facilitates the binding of SIX3 to the core DNA motif of SIX3 promoter (By similarity). Interacts with EYA1; promotes EYA1 translocation to the nucleus (By similarity). Interacts with TLE1 and AES (via Q domain); can act in combination with either TLE1 and/or AES leading to transcriptional repression or activation, respectively. Interacts (via homeobox) with NR4A3; differentially regulates the transcriptional activities NR4A3. Interacts with GMNN. Interacts with TLE4.

neXtProt entry for SIX3 Gene

Post-translational modifications for SIX3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SIX3 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for SIX3 Gene

Domains & Families for SIX3 Gene

Gene Families for SIX3 Gene

Suggested Antigen Peptide Sequences for SIX3 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

O95343

UniProtKB/Swiss-Prot:

SIX3_HUMAN :
  • Belongs to the SIX/Sine oculis homeobox family.
Family:
  • Belongs to the SIX/Sine oculis homeobox family.
genes like me logo Genes that share domains with SIX3: view

Function for SIX3 Gene

Molecular function for SIX3 Gene

GENATLAS Biochemistry:
Drosophila sine oculis homolog SIX3,homeo box encoding gene,expressed very early during eye development in midline forebrain and in anterior region of the neural plate especially inner retina and later in ganglion cells and in cells of the inner nuclear layer,involved in regulation of eye development
UniProtKB/Swiss-Prot Function:
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.

Gene Ontology (GO) - Molecular Function for SIX3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000980 RNA polymerase II distal enhancer sequence-specific DNA binding IEA --
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding IEA --
GO:0001205 transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding IEA --
GO:0001222 transcription corepressor binding IPI 12441302
GO:0003677 DNA binding IEA --
genes like me logo Genes that share ontologies with SIX3: view
genes like me logo Genes that share phenotypes with SIX3: view

Human Phenotype Ontology for SIX3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SIX3 Gene

MGI Knock Outs for SIX3:

Animal Model Products

CRISPR Products

miRNA for SIX3 Gene

miRTarBase miRNAs that target SIX3

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for SIX3 Gene

Localization for SIX3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SIX3 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SIX3 gene
Compartment Confidence
nucleus 5
cytosol 2
cytoskeleton 1
mitochondrion 1

Gene Ontology (GO) - Cellular Components for SIX3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
genes like me logo Genes that share ontologies with SIX3: view

Pathways & Interactions for SIX3 Gene

genes like me logo Genes that share pathways with SIX3: view

Pathways by source for SIX3 Gene

Gene Ontology (GO) - Biological Process for SIX3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000060 protein import into nucleus, translocation ISS --
GO:0001654 eye development IDA 18791198
GO:0002070 epithelial cell maturation ISS,IEA --
GO:0002088 lens development in camera-type eye IEA,ISS --
GO:0003404 optic vesicle morphogenesis ISS,IEA --
genes like me logo Genes that share ontologies with SIX3: view

No data available for SIGNOR curated interactions for SIX3 Gene

Transcripts for SIX3 Gene

mRNA/cDNA for SIX3 Gene

(1) REFSEQ mRNAs :
(3) Additional mRNA sequences :
(42) Selected AceView cDNA sequences:
(1) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for SIX3 Gene

SIX homeobox 3:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for SIX3 Gene

No ASD Table

Relevant External Links for SIX3 Gene

GeneLoc Exon Structure for
SIX3
ECgene alternative splicing isoforms for
SIX3

Expression for SIX3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SIX3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SIX3 Gene

This gene is overexpressed in Brain - Nucleus accumbens (basal ganglia) (x12.9), Brain - Putamen (basal ganglia) (x12.1), Brain - Caudate (basal ganglia) (x10.4), Pituitary (x7.6), and Brain - Hypothalamus (x4.5).

Protein differential expression in normal tissues from HIPED for SIX3 Gene

This gene is overexpressed in Heart (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for SIX3 Gene



Protein tissue co-expression partners for SIX3 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of SIX3 Gene:

SIX3

SOURCE GeneReport for Unigene cluster for SIX3 Gene:

Hs.567336

Evidence on tissue expression from TISSUES for SIX3 Gene

  • Eye(4.7)
  • Nervous system(2.7)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SIX3 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • endocrine
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Organs:
Head and neck:
  • brain
  • cerebellum
  • cheek
  • cranial nerve
  • eye
  • face
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • mouth
  • nose
  • pharynx
  • pituitary gland
  • skull
  • tooth
Thorax:
  • lung
  • rib
  • rib cage
Abdomen:
  • adrenal gland
  • intestine
  • large intestine
Pelvis:
  • pelvis
  • rectum
  • urinary bladder
General:
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • spinal cord
  • vertebrae
genes like me logo Genes that share expression patterns with SIX3: view

Primer Products

No data available for mRNA Expression by UniProt/SwissProt for SIX3 Gene

Orthologs for SIX3 Gene

This gene was present in the common ancestor of animals.

Orthologs for SIX3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SIX3 34 35
  • 98 (n)
cow
(Bos Taurus)
Mammalia SIX3 34 35
  • 96.95 (n)
rat
(Rattus norvegicus)
Mammalia Six3 34
  • 94.48 (n)
mouse
(Mus musculus)
Mammalia Six3 34 16 35
  • 94.28 (n)
oppossum
(Monodelphis domestica)
Mammalia SIX3 35
  • 94 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SIX3 34 35
  • 93.96 (n)
chicken
(Gallus gallus)
Aves SIX3 34
  • 85.2 (n)
lizard
(Anolis carolinensis)
Reptilia SIX3 35
  • 88 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia six3 34
  • 84.24 (n)
African clawed frog
(Xenopus laevis)
Amphibia six3-A 34
zebrafish
(Danio rerio)
Actinopterygii six3b 35
  • 83 (a)
OneToMany
six3a 34 35
  • 78.91 (n)
fruit fly
(Drosophila melanogaster)
Insecta Optix 36 35
  • 74 (a)
Six4 36
  • 55 (a)
worm
(Caenorhabditis elegans)
Secernentea ceh-32 36
  • 65 (a)
ceh-33 36
  • 52 (a)
ceh-34 36 35
  • 45 (a)
ceh-35 36
  • 37 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 43 (a)
OneToMany
Species where no ortholog for SIX3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SIX3 Gene

ENSEMBL:
Gene Tree for SIX3 (if available)
TreeFam:
Gene Tree for SIX3 (if available)

Paralogs for SIX3 Gene

Paralogs for SIX3 Gene

(6) SIMAP similar genes for SIX3 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with SIX3: view

Variants for SIX3 Gene

Sequence variations from dbSNP and Humsavar for SIX3 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type
rs121917878 Pathogenic, Holoprosencephaly 2 (HPE2) [MIM:157170] 44,942,780(+) GGTAC(C/G)TACAG upstream-variant-2KB, reference, missense
rs121917879 Pathogenic, Holoprosencephaly 2 (HPE2) [MIM:157170] 44,942,874(+) GAACC(C/G)GCGGC upstream-variant-2KB, reference, missense
rs121917880 Pathogenic, Holoprosencephaly 2 (HPE2) [MIM:157170] 44,942,853(+) ACAAG(C/T)AGGCA upstream-variant-2KB, reference, missense
rs121917881 Pathogenic, Holoprosencephaly 2 (HPE2) [MIM:157170] 44,942,310(+) CGGCG(A/G)CTCCA upstream-variant-2KB, reference, missense
rs137853021 Pathogenic, Holoprosencephaly 2 (HPE2) [MIM:157170] 44,942,443(+) CTCTG(G/T)TCGCT upstream-variant-2KB, reference, missense

Structural Variations from Database of Genomic Variants (DGV) for SIX3 Gene

Variant ID Type Subtype PubMed ID
nsv457207 CNV loss 19166990
nsv526534 CNV loss 19592680
nsv581702 CNV loss 21841781
nsv953779 CNV deletion 24416366

Variation tolerance for SIX3 Gene

Residual Variation Intolerance Score: 53.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.16; 23.42% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for SIX3 Gene

Human Gene Mutation Database (HGMD)
SIX3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SIX3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SIX3 Gene

Disorders for SIX3 Gene

MalaCards: The human disease database

(33) MalaCards diseases for SIX3 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
schizencephaly
  • familial schizencephaly
holoprosencephaly-2
  • holoprosencephaly 2
single median maxillary central incisor
  • solitary median maxillary central incisor
midline interhemispheric variant of holoprosencephaly
  • mih
septopreoptic holoprosencephaly
  • septopreoptic hpe
- elite association - COSMIC cancer census association via MalaCards
Search SIX3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SIX3_HUMAN
  • Holoprosencephaly 2 (HPE2) [MIM:157170]: A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. {ECO:0000269 PubMed:10369266, ECO:0000269 PubMed:15221788, ECO:0000269 PubMed:15523651, ECO:0000269 PubMed:17001667, ECO:0000269 PubMed:18791198, ECO:0000269 PubMed:20531442}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Schizencephaly (SCHZC) [MIM:269160]: Extremely rare human congenital disorder characterized by a full-thickness cleft within the cerebral hemispheres. These clefts are lined with gray matter and most commonly involve the parasylvian regions. Large portions of the cerebral hemispheres may be absent and replaced by cerebro-spinal fluid. {ECO:0000269 PubMed:20157829}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for SIX3

Genetic Association Database (GAD)
SIX3
Human Genome Epidemiology (HuGE) Navigator
SIX3
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
SIX3
genes like me logo Genes that share disorders with SIX3: view

No data available for Genatlas for SIX3 Gene

Publications for SIX3 Gene

  1. Genomic cloning, structure, expression pattern, and chromosomal location of the human SIX3 gene. (PMID: 9889003) Granadino B. … Rodriguez de Cordoba S. (Genomics 1999) 2 3 4 22 64
  2. Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly. (PMID: 10369266) Wallis D.E. … Muenke M. (Nat. Genet. 1999) 2 3 4 22 64
  3. Mutational screening of 10 genes in Chinese patients with microphthalmia and/or coloboma. (PMID: 20057906) Zhang X. … Zhang Q. (Mol. Vis. 2009) 3 22 46 64
  4. Mutations in the human SIX3 gene in holoprosencephaly are loss of function. (PMID: 18791198) DomenAc S. … Feldman B. (Hum. Mol. Genet. 2008) 3 4 22 64
  5. Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: mutation review and genotype-phenotype correlations. (PMID: 15221788) Dubourg C. … David V. (Hum. Mutat. 2004) 3 4 22 64

Products for SIX3 Gene

Sources for SIX3 Gene

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