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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. Gene Ontology (GO) annotations related to this gene include DNA binding transcription factor activity 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

Additional gene information for SIX2 Gene

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

Genomics for SIX2 Gene

GeneHancer (GH) Regulatory Elements for SIX2 Gene

Promoters and enhancers for SIX2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02I045006 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 559.4 +0.6 630 4.4 PKNOX1 SIN3A ZNF2 ZBTB7B BRCA1 ETS1 GLIS2 ZNF143 SP3 TSHZ1 SIX2 SRBD1 ENSG00000231156 LOC730043 GC02P044973
GH02I045240 Enhancer 1.2 Ensembl ENCODE dbSUPER 15.9 -232.0 -232039 3.1 PKNOX1 BMI1 ZNF2 ZEB1 ZNF335 ZNF366 SCRT2 RCOR1 ATF7 ZNF391 SIX2 LOC105374576 GC02P045291 LINC01121
GH02I045167 Promoter/Enhancer 1.6 Ensembl ENCODE dbSUPER 10.7 -161.8 -161756 7.3 PKNOX1 SIN3A ZNF76 FEZF1 BATF RAD21 BRCA1 RFX5 ZNF335 GLIS2 SIX2 ENSG00000231054 LOC105374576 LINC01121
GH02I045469 Enhancer 1.1 Ensembl ENCODE 10.9 -460.6 -460635 1.8 FOXA2 YY1 RXRA MIER2 REST KAT8 NFIL3 SSRP1 MIER3 RFX3 SRBD1 SIX2 GC02P045456 RN7SL414P
GH02I045012 Enhancer 1.1 Ensembl ENCODE dbSUPER 7.7 -4.2 -4182 2.5 RING1 CTCF PKNOX1 USF1 SUZ12 SIN3A ZIC2 RAD21 ZNF335 POLR2A ENSG00000231156 SIX2 GC02P045034 GC02P044973
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around SIX2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SIX2 gene promoter:

Genomic Locations for SIX2 Gene

Genomic Locations for SIX2 Gene
chr2:45,005,161-45,009,610
(GRCh38/hg38)
Size:
4,450 bases
Orientation:
Minus strand
chr2:45,232,300-45,236,569
(GRCh37/hg19)

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

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

Suggested Antigen Peptide Sequences for SIX2 Gene

Graphical View of Domain Structure for InterPro Entry

Q9NPC8

UniProtKB/Swiss-Prot:

SIX2_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 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 proximal promoter sequence-specific DNA binding IEA --
GO:0001077 transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding IEA --
GO:0003677 DNA binding IEA --
GO:0003700 DNA binding transcription factor activity IEA,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

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , 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
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 SIX2 gene
Compartment Confidence
nucleus 5
plasma membrane 2
cytosol 2
extracellular 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
  • Nuclear membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SIX2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
genes like me logo Genes that share ontologies with SIX2: view

Pathways & Interactions 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 ISS,IEA --
GO:0002062 chondrocyte differentiation IEA --
GO:0003337 mesenchymal to epithelial transition involved in metanephros morphogenesis ISS,IEA --
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

Drugs & Compounds for SIX2 Gene

No Compound Related Data Available

Transcripts for SIX2 Gene

mRNA/cDNA for SIX2 Gene

Unigene Clusters for SIX2 Gene

SIX homeobox 2:
Representative Sequences:

Inhibitory RNA 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 from GTEx, Illumina, BioGPS, and CGAP SAGE 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).

Evidence on tissue expression from TISSUES for SIX2 Gene

  • Kidney(2.8)
  • Muscle(2.1)
genes like me logo Genes that share expression patterns with SIX2: view

No data available for Protein differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer 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 33 34
  • 100 (n)
oppossum
(Monodelphis domestica)
Mammalia SIX2 34
  • 97 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SIX2 33 34
  • 93.47 (n)
dog
(Canis familiaris)
Mammalia SIX2 33 34
  • 93.47 (n)
mouse
(Mus musculus)
Mammalia Six2 33 16 34
  • 92.33 (n)
rat
(Rattus norvegicus)
Mammalia Six2 33
  • 91.75 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia SIX2 34
  • 91 (a)
OneToOne
chicken
(Gallus gallus)
Aves SIX2 33 34
  • 83.92 (n)
lizard
(Anolis carolinensis)
Reptilia SIX2 34
  • 92 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia six2 33
  • 76.64 (n)
African clawed frog
(Xenopus laevis)
Amphibia six2-A 33
zebrafish
(Danio rerio)
Actinopterygii six2b 34
  • 80 (a)
OneToMany
six2a 33 34
  • 74.04 (n)
-- 33
fruit fly
(Drosophila melanogaster)
Insecta so 35 34
  • 86 (a)
Six4 35
  • 62 (a)
worm
(Caenorhabditis elegans)
Secernentea ceh-33 35 34
  • 59 (a)
ceh-32 35
  • 54 (a)
ceh-34 35
  • 52 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 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 Variation AA Info Type
rs372153489 uncertain-significance, Congenital anomalies of kidney and urinary tract 45,006,339(-) G/A coding_sequence_variant, missense_variant
rs756635283 likely-pathogenic, not provided 45,006,286(-) C/T coding_sequence_variant, missense_variant
rs1000075535 -- 45,006,659(-) G/A intron_variant
rs1000529074 -- 45,010,727(-) G/C/T upstream_transcript_variant
rs1000897434 -- 45,011,209(-) C/T upstream_transcript_variant

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)

Additional Variant Information for SIX2 Gene

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

SNP Genotyping and Copy Number Assay Products

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

Disorders for SIX2 Gene

MalaCards: The human disease database

(4) MalaCards diseases for SIX2 Gene - From: HGMD, Orphanet, and DISEASES

- elite association - COSMIC cancer census association via MalaCards
Search SIX2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for 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 CA … Bailey ME (Gene 2000) 3 4 22 58
  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 (Human pathology 2013) 3 4 58
  3. SIX2 and CITED1, markers of nephronic progenitor self-renewal, remain active in primitive elements of Wilms' tumor. (PMID: 22703800) Murphy AJ … Lovvorn HN (Journal of pediatric surgery 2012) 3 4 58
  4. SIX2 and BMP4 mutations associate with anomalous kidney development. (PMID: 18305125) Weber S … Burdine RD (Journal of the American Society of Nephrology : JASN 2008) 3 4 58
  5. Familial syndromic esophageal atresia maps to 2p23-p24. (PMID: 10677303) Celli J … Brunner HG (American journal of human genetics 2000) 3 4 58

Products for SIX2 Gene

Sources for SIX2 Gene

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