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] See more...

Aliases for SIX2 Gene

Aliases for SIX2 Gene

  • SIX Homeobox 2 2 3 5
  • Sine Oculis Homeobox Homolog 2 3 4
  • Homeobox Protein SIX2 3 4
  • Sine Oculis Homeobox (Drosophila) Homolog 2 2
  • Sine Oculis Homeobox Homolog 2 (Drosophila) 2

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 Renal Hypoplasia. 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 Summary 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 , Rfam classification 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
GH02J045006 Promoter/Enhancer 2.3 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 509.3 +1.2 1210 5.6 ZNF217 TCF12 ZFX ZNF639 ZIC2 POLR2A ZBTB10 CLOCK GABPA ZBTB26 SIX2 SRBD1 ENSG00000231156 HSALNG0014619
GH02J045167 Promoter/Enhancer 1.5 Ensembl ENCODE CraniofacialAtlas dbSUPER 10.7 -161.8 -161756 7.3 CTCF ZSCAN5C USF1 FOS POLR2A ZBTB26 MXI1 ZNF341 EZH2 DEK ENSG00000286728 SIX2 ENSG00000231054 ENSG00000286519 LINC01121
GH02J045240 Enhancer 1 ENCODE dbSUPER 15.9 -232.0 -232039 3.1 EP300 USF1 JUND TRIM28 RFX1 ATF2 ZEB1 OSR2 RAD51 BCL11A SIX2 LOC105374576 hsa-miR-1273e-039 LINC01121
GH02J044981 Enhancer 0.7 Ensembl 19.2 +27.8 27809 0.8 CTCF REST RAD21 SKI TRIM22 SMC3 DEK TCF12 ZBTB17 ZNF263 SIX2 ENSG00000231156 5MWI_A-095 ENSG00000231848
GH02J045469 Enhancer 1 Ensembl ENCODE 10.9 -460.5 -460474 2.2 EP300 FOXK2 TCF12 NCOR1 TCF7 FOXA1 ZBTB25 TGIF2 SKI TEAD1 SRBD1 SIX2 RF00994-480 piR-32214-373 lnc-SIX2-8
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SIX2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SIX2

Top Transcription factor binding sites by QIAGEN in the SIX2 gene promoter:
  • CUTL1
  • IRF-7A
  • ITF-2
  • N-Myc
  • NF-1
  • NF-1/L
  • NF-kappaB1
  • Nkx2-5
  • STAT5A
  • Tal-1beta

Genomic Locations for SIX2 Gene

Genomic Locations for SIX2 Gene
chr2:45,005,182-45,009,610
(GRCh38/hg38)
Size:
4,429 bases
Orientation:
Minus strand
chr2:45,232,300-45,236,569
(GRCh37/hg19)
Size:
4,270 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

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

Protein Domains for SIX2 Gene

Blocks:
  • Lambda and other repressor helix-turn-helix signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for SIX2 Gene

GenScript: Design optimal peptide antigens:
  • SIX homeobox 2 (Q8TBA2_HUMAN)
  • Sine oculis homeobox homolog 2 (SIX2_HUMAN)

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

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.
GENATLAS Biochemistry:
Drosophila sine oculis homolog SIX2 homeo box encoding gene,expressed in mesenchyme in mouse

Phenotypes From GWAS Catalog for SIX2 Gene

Gene Ontology (GO) - Molecular Function for SIX2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000976 transcription regulatory region sequence-specific DNA binding IBA 21873635
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IEA --
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific NAS 19274049
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IEA --
GO:0003677 DNA binding IEA --
genes like me logo Genes that share ontologies with SIX2: view
genes like me logo Genes that share phenotypes with SIX2: view

Human Phenotype Ontology for SIX2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SIX2 Gene

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

Animal Model Products

CRISPR 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

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SIX2

No data available for Enzyme Numbers (IUBMB) 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 3
cytosol 3
extracellular 2
cytoskeleton 2
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 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:0000790 nuclear chromatin ISA --
GO:0005634 nucleus IBA 21873635
GO:0005667 transcription factor complex IBA 21873635
genes like me logo Genes that share ontologies with SIX2: view

Pathways & Interactions for SIX2 Gene

PathCards logo

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

Drugs & Compounds for SIX2 Gene

No Compound Related Data Available

Transcripts for SIX2 Gene

mRNA/cDNA for SIX2 Gene

1 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SIX2

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

No ASD Table

Relevant External Links for SIX2 Gene

GeneLoc Exon Structure for
SIX2

Expression for SIX2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and 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, MaxQB, and MOPED for SIX2 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for 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 31 30
  • 100 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SIX2 31
  • 97 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SIX2 31 30
  • 93.47 (n)
OneToOne
dog
(Canis familiaris)
Mammalia SIX2 31 30
  • 93.47 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Six2 17 31 30
  • 92.33 (n)
rat
(Rattus norvegicus)
Mammalia Six2 30
  • 91.75 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia SIX2 31
  • 91 (a)
OneToOne
chicken
(Gallus gallus)
Aves SIX2 31 30
  • 83.92 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SIX2 31
  • 92 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia six2 30
  • 76.64 (n)
African clawed frog
(Xenopus laevis)
Amphibia six2-A 30
zebrafish
(Danio rerio)
Actinopterygii six2b 31
  • 80 (a)
OneToMany
six2a 31 30
  • 74.04 (n)
OneToMany
-- 30
fruit fly
(Drosophila melanogaster)
Insecta Six4 32
  • 62 (a)
so 31 32
  • 42 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea ceh-32 32
  • 54 (a)
ceh-34 32
  • 52 (a)
ceh-33 31 32
  • 44 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 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)
Aminode:
Evolutionary constrained regions (ECRs) for SIX2: view image

Paralogs for SIX2 Gene

Paralogs for SIX2 Gene

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

  • SIX2_HUMAN
  • Q8TBA2_HUMAN
genes like me logo Genes that share paralogs with SIX2: view

Variants for SIX2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SIX2 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
rs1558440805 Uncertain Significance: not provided 45,008,774(-) G/A MISSENSE_VARIANT
rs372153489 Uncertain Significance: Congenital anomalies of kidney and urinary tract 45,006,339(-) G/A MISSENSE_VARIANT
rs756635283 Likely Pathogenic: not provided 45,006,286(-) C/T MISSENSE_VARIANT
rs773807534 Uncertain Significance: not provided 45,006,187(-) C/T MISSENSE_VARIANT
rs142188105 - p.Leu43Phe

Additional dbSNP identifiers (rs#s) for SIX2 Gene

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

(15) MalaCards diseases for SIX2 Gene - From: Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
six2-related frontonasal dysplasia
  • six2-related fnd
renal hypoplasia
duodenogastric reflux
renal hypodysplasia/aplasia 1
  • rhda1
townes-brocks syndrome
  • renal-ear-anal-radial syndrome
- 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 23 54
  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 54
  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 54
  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 54
  5. Familial syndromic esophageal atresia maps to 2p23-p24. (PMID: 10677303) Celli J … Brunner HG (American journal of human genetics 2000) 3 4 54

Products for SIX2 Gene

Sources for SIX2 Gene