Free for academic non-profit institutions. Other users need a Commercial license

Aliases for SIX2 Gene

Aliases for SIX2 Gene

  • SIX Homeobox 2 2 3 5
  • Sine Oculis Homeobox (Drosophila) Homolog 2 2
  • Sine Oculis Homeobox Homolog 2 (Drosophila) 2
  • Sine Oculis Homeobox Homolog 2 4

External Ids for SIX2 Gene

Previous GeneCards Identifiers for SIX2 Gene

  • GC02M045231
  • GC02M045401
  • GC02M045206
  • GC02M045143
  • GC02M045232
  • GC02M044969

Summaries for SIX2 Gene

Entrez Gene Summary for SIX2 Gene

  • This gene is a member of the vertebrate gene family which encode proteins homologous to the Drosophila 'sine oculis' homeobox protein. The encoded protein is a transcription factor which, like other members of this gene family, may be involved in limb or eye development. [provided by RefSeq, Dec 2008]

GeneCards Summary for SIX2 Gene

SIX2 (SIX Homeobox 2) is a Protein Coding gene. Diseases associated with SIX2 include Six2-Related Frontonasal Dysplasia and Duodenal Disease. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and transcription factor binding. An important paralog of this gene is SIX1.

UniProtKB/Swiss-Prot for SIX2 Gene

  • Transcription factor that plays an important role in the development of several organs, including kidney, skull and stomach. During kidney development, maintains cap mesenchyme multipotent nephron progenitor cells in an undifferentiated state by opposing the inductive signals emanating from the ureteric bud and cooperates with WNT9B to promote renewing progenitor cells proliferation. Acts through its interaction with TCF7L2 and OSR1 in a canonical Wnt signaling independent manner preventing transcription of differentiation genes in cap mesenchyme such as WNT4. Also acts independently of OSR1 to activate expression of many cap mesenchyme genes, including itself, GDNF and OSR1. During craniofacial development plays a role in growth and elongation of the cranial base through regulation of chondrocyte differentiation. During stomach organogenesis, controls pyloric sphincter formation and mucosal growth through regulation of a gene network including NKX2-5, BMPR1B, BMP4, SOX9 and GREM1. During branchial arch development, acts to mediate HOXA2 control over the insulin-like growth factor pathway. Also may be involved in limb tendon and ligament development (By similarity). Plays a role in cell proliferation and migration.

Gene Wiki entry for SIX2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SIX2 Gene

Genomics for SIX2 Gene

Regulatory Elements for SIX2 Gene

Enhancers for SIX2 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
GH02F045240 1.1 Ensembl ENCODE 15.9 -232.0 -232040 3.1 PKNOX1 ARID4B ZNF2 YY1 ZNF121 MIER2 TSHZ1 KAT8 NFIL3 MIER3 SIX2 LOC105374576 GC02P045291
GH02F045469 0.9 Ensembl ENCODE 10.9 -460.6 -460636 1.8 ELF3 RAD21 DNMT3B RARA CREM HMG20B CEBPB MIER2 ZNF843 NR2F2 SRBD1 SIX2 GC02P045456 RN7SL414P
GH02F045167 0.5 ENCODE 10.7 -161.8 -161757 7.3 PKNOX1 ZNF76 SIN3A FEZF1 RAD21 BRCA1 RFX5 GLIS2 SCRT2 RCOR1 SIX2 ENSG00000231054 LOC105374576
GH02F045006 1.1 FANTOM5 ENCODE 9.4 +0.6 631 4.4 PKNOX1 ARID4B SIN3A BRCA1 ZNF2 ETS1 GLIS2 FOS ZNF263 SP3 SIX2 ENSG00000231156 LOC730043
GH02F045013 0.6 ENCODE 7.7 -4.7 -4672 1.6 PKNOX1 SIN3A ZNF2 RAD21 ZNF366 ZNF263 ZNF362 CEBPB ZNF843 CBX8 ENSG00000231156 SIX2 GC02P045034
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around SIX2 on UCSC Golden Path with GeneCards custom track

Promoters for SIX2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000589422 110 2601 PKNOX1 SIN3A BRCA1 ZNF2 ETS1 GLIS2 ZNF263 SP3 TSHZ1 CBX8

Genomic Location for SIX2 Gene

Chromosome:
2
Start:
45,005,161 bp from pter
End:
45,009,610 bp from pter
Size:
4,450 bases
Orientation:
Minus strand

Genomic View for SIX2 Gene

Genes around SIX2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SIX2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SIX2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SIX2 Gene

Proteins for SIX2 Gene

  • Protein details for SIX2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NPC8-SIX2_HUMAN
    Recommended name:
    Homeobox protein SIX2
    Protein Accession:
    Q9NPC8
    Secondary Accessions:
    • Q9BXH7

    Protein attributes for SIX2 Gene

    Size:
    291 amino acids
    Molecular mass:
    32286 Da
    Quaternary structure:
    • Interacts with TCF7L2; in a canonical Wnt signaling independent manner; prevents transcription of differentiation genes in cap mesenchyme. Interacts with OSR1; form a strong repressor complex with TCF7L2, TLE2 and TLE3 to prevent the activation of Wnt/beta-catenin target genes in the cap mesenchyme. Interacts with HOXA11, EYA1 and EYA3.

neXtProt entry for SIX2 Gene

Post-translational modifications for SIX2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SIX2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for SIX2 Gene

Domains & Families for SIX2 Gene

Gene Families for SIX2 Gene

Suggested Antigen Peptide Sequences for SIX2 Gene

Graphical View of Domain Structure for InterPro Entry

Q9NPC8

UniProtKB/Swiss-Prot:

SIX2_HUMAN :
  • Contains 1 homeobox DNA-binding domain.
  • Belongs to the SIX/Sine oculis homeobox family.
Domain:
  • Contains 1 homeobox DNA-binding domain.
Family:
  • Belongs to the SIX/Sine oculis homeobox family.
genes like me logo Genes that share domains with SIX2: view

Function for SIX2 Gene

Molecular function for SIX2 Gene

GENATLAS Biochemistry:
Drosophila sine oculis homolog SIX2 homeo box encoding gene,expressed in mesenchyme in mouse
UniProtKB/Swiss-Prot Function:
Transcription factor that plays an important role in the development of several organs, including kidney, skull and stomach. During kidney development, maintains cap mesenchyme multipotent nephron progenitor cells in an undifferentiated state by opposing the inductive signals emanating from the ureteric bud and cooperates with WNT9B to promote renewing progenitor cells proliferation. Acts through its interaction with TCF7L2 and OSR1 in a canonical Wnt signaling independent manner preventing transcription of differentiation genes in cap mesenchyme such as WNT4. Also acts independently of OSR1 to activate expression of many cap mesenchyme genes, including itself, GDNF and OSR1. During craniofacial development plays a role in growth and elongation of the cranial base through regulation of chondrocyte differentiation. During stomach organogenesis, controls pyloric sphincter formation and mucosal growth through regulation of a gene network including NKX2-5, BMPR1B, BMP4, SOX9 and GREM1. During branchial arch development, acts to mediate HOXA2 control over the insulin-like growth factor pathway. Also may be involved in limb tendon and ligament development (By similarity). Plays a role in cell proliferation and migration.

Gene Ontology (GO) - Molecular Function for SIX2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding IEA --
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding IEA --
GO:0003677 DNA binding IEA --
GO:0003700 transcription factor activity, sequence-specific DNA binding NAS 10773454
GO:0008134 transcription factor binding IEA --
genes like me logo Genes that share ontologies with SIX2: view
genes like me logo Genes that share phenotypes with SIX2: view

Animal Models for SIX2 Gene

MGI Knock Outs for SIX2:
  • Six2 tm1(tTA,tetO-EGFP/cre)Amc
  • Six2 tm1Gco

Animal Model Products

miRNA for SIX2 Gene

miRTarBase miRNAs that target SIX2
Targeted motifs for SIX2 Gene
HOMER Transcription Factor Regulatory Elements motif SIX2
  • Consensus sequence: GWAAYHTGAKMC Submotif: canonical Cell Type: NephronProgenitor GEO ID: GSE39837

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology and Transcription Factor Targets for SIX2 Gene

Localization for SIX2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SIX2 Gene

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SIX2 Gene COMPARTMENTS Subcellular localization image for SIX2 gene
Compartment Confidence
nucleus 5
plasma membrane 5
cytosol 2
extracellular 1

Gene Ontology (GO) - Cellular Components for SIX2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA --
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IDA --
GO:0005886 plasma membrane IDA --
GO:0031965 nuclear membrane IDA --
genes like me logo Genes that share ontologies with SIX2: view

Pathways & Interactions for SIX2 Gene

SuperPathways for SIX2 Gene

No Data Available

Gene Ontology (GO) - Biological Process for SIX2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001656 metanephros development IEA --
GO:0001822 kidney development IEA,ISS --
GO:0002062 chondrocyte differentiation IEA --
GO:0003337 mesenchymal to epithelial transition involved in metanephros morphogenesis IEA,ISS --
GO:0006355 regulation of transcription, DNA-templated IEA --
genes like me logo Genes that share ontologies with SIX2: view

No data available for Pathways by source and SIGNOR curated interactions for SIX2 Gene

Transcripts for SIX2 Gene

mRNA/cDNA for SIX2 Gene

Unigene Clusters for SIX2 Gene

SIX homeobox 2:
Representative Sequences:

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for SIX2 Gene

No ASD Table

Relevant External Links for SIX2 Gene

GeneLoc Exon Structure for
SIX2
ECgene alternative splicing isoforms for
SIX2

Expression for SIX2 Gene

mRNA expression in normal human tissues for SIX2 Gene

mRNA differential expression in normal tissues according to GTEx for SIX2 Gene

This gene is overexpressed in Muscle - Skeletal (x14.2), Stomach (x5.3), and Pituitary (x4.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for SIX2 Gene



NURSA nuclear receptor signaling pathways regulating expression of SIX2 Gene:

SIX2

SOURCE GeneReport for Unigene cluster for SIX2 Gene:

Hs.101937

mRNA Expression by UniProt/SwissProt for SIX2 Gene:

Q9NPC8-SIX2_HUMAN
Tissue specificity: Strongly expressed in skeletal muscle. Expressed in Wilms tumor and in the cap mesenchyme of fetal kidney (at protein level).
genes like me logo Genes that share expression patterns with SIX2: view

Primer Products

No data available for Protein differential expression in normal tissues and Protein tissue co-expression partners for SIX2 Gene

Orthologs for SIX2 Gene

This gene was present in the common ancestor of animals.

Orthologs for SIX2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SIX2 34 35
  • 100 (n)
oppossum
(Monodelphis domestica)
Mammalia SIX2 35
  • 97 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SIX2 34 35
  • 93.47 (n)
dog
(Canis familiaris)
Mammalia SIX2 34 35
  • 93.47 (n)
mouse
(Mus musculus)
Mammalia Six2 34 16 35
  • 92.33 (n)
rat
(Rattus norvegicus)
Mammalia Six2 34
  • 91.75 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia SIX2 35
  • 91 (a)
OneToOne
chicken
(Gallus gallus)
Aves SIX2 34 35
  • 83.92 (n)
lizard
(Anolis carolinensis)
Reptilia SIX2 35
  • 92 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia six2 34
  • 76.64 (n)
African clawed frog
(Xenopus laevis)
Amphibia six2-A 34
zebrafish
(Danio rerio)
Actinopterygii six2b 35
  • 80 (a)
OneToMany
six2a 34 35
  • 74.04 (n)
-- 34
fruit fly
(Drosophila melanogaster)
Insecta so 36 35
  • 86 (a)
Six4 36
  • 62 (a)
worm
(Caenorhabditis elegans)
Secernentea ceh-33 36 35
  • 59 (a)
ceh-32 36
  • 54 (a)
ceh-34 36
  • 52 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 46 (a)
OneToOne
Species where no ortholog for SIX2 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)
  • 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 SIX2 Gene

ENSEMBL:
Gene Tree for SIX2 (if available)
TreeFam:
Gene Tree for SIX2 (if available)

Paralogs for SIX2 Gene

Paralogs for SIX2 Gene

(6) SIMAP similar genes for SIX2 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with SIX2: view

Variants for SIX2 Gene

Sequence variations from dbSNP and Humsavar for SIX2 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type
rs111286084 -- 45,010,203(+) AAAGA(A/G)ATGGG upstream-variant-2KB
rs111604503 -- 45,008,157(+) AAGCA(C/T)CACCA intron-variant
rs1118180 -- 45,008,463(-) GAGGC(A/C)TAAAC intron-variant
rs112083430 -- 45,011,130(+) TTCTC(C/T)GCAAG upstream-variant-2KB
rs112423728 -- 45,005,400(+) CGTAT(A/G)ACGAG utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for SIX2 Gene

Variant ID Type Subtype PubMed ID
nsv2711 CNV deletion 18451855
nsv953780 CNV deletion 24416366

Variation tolerance for SIX2 Gene

Residual Variation Intolerance Score: 49% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.11; 22.51% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for SIX2 Gene

Human Gene Mutation Database (HGMD)
SIX2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SIX2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SIX2 Gene

Disorders for SIX2 Gene

MalaCards: The human disease database

(3) MalaCards diseases for SIX2 Gene - From: GeneTests and DISEASES

Disorder Aliases PubMed IDs
six2-related frontonasal dysplasia
duodenal disease
  • duodenum disorder
renal hypodysplasia/aplasia 1
  • renal agenesis
- elite association - COSMIC cancer census association via MalaCards
Search SIX2 in MalaCards View complete list of genes associated with diseases

Relevant External Links for SIX2

Genetic Association Database (GAD)
SIX2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
SIX2
genes like me logo Genes that share disorders with SIX2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SIX2 Gene

Publications for SIX2 Gene

  1. Structure, mapping and expression of the human gene encoding the homeodomain protein, SIX2. (PMID: 10773454) Boucher C.A. … Bailey M.E.S. (Gene 2000) 3 4 22 64
  2. The pluripotent renal stem cell regulator SIX2 is activated in renal neoplasms and influences cellular proliferation and migration. (PMID: 22995329) Senanayake U. … Guertl B. (Hum. Pathol. 2013) 3 4 64
  3. SIX2 and CITED1, markers of nephronic progenitor self-renewal, remain active in primitive elements of Wilms' tumor. (PMID: 22703800) Murphy A.J. … Lovvorn H.N. (J. Pediatr. Surg. 2012) 3 4 64
  4. SIX2 and BMP4 mutations associate with anomalous kidney development. (PMID: 18305125) Weber S. … Burdine R.D. (J. Am. Soc. Nephrol. 2008) 3 4 64
  5. Familial syndromic esophageal atresia maps to 2p23-p24. (PMID: 10677303) Celli J. … Brunner H.G. (Am. J. Hum. Genet. 2000) 3 4 64

Products for SIX2 Gene

Sources for SIX2 Gene

Content
Loading form....