The protein encoded by this gene is a homeobox protein that is similar to the Drosophila 'sine oculis' gene product. This gene is found in a cluster of related genes on chromosome 14 and is thought to be involved in eye development. Defects in this gene are a cause of isolated microphthalmia with cataract type 2 (MCOPCT2). [provided by RefSeq, Jul 2008] See more...

Aliases for SIX6 Gene

Aliases for SIX6 Gene

  • SIX Homeobox 6 2 3 5
  • Sine Oculis Homeobox Homolog 6 3 4
  • Homeodomain Protein OPTX2 3 4
  • Homeobox Protein SIX6 3 4
  • Optic Homeobox 2 3 4
  • OPTX2 3 4
  • Sine Oculis Homeobox (Drosophila) Homolog 6 2
  • Sine Oculis Homeobox Homolog 6 (Drosophila) 2
  • Sine Oculis Homeobox-Like Protein 6 3
  • Sine Oculis Homeobox Protein 6 3
  • MCOPCT2 3
  • ODRMD 3
  • Six9 3
  • SIX9 4

External Ids for SIX6 Gene

Previous HGNC Symbols for SIX6 Gene

  • OPTX2

Previous GeneCards Identifiers for SIX6 Gene

  • GC14P058302
  • GC14P054770
  • GC14P058965
  • GC14P058966
  • GC14P060045
  • GC14P060975
  • GC14P041139

Summaries for SIX6 Gene

Entrez Gene Summary for SIX6 Gene

  • The protein encoded by this gene is a homeobox protein that is similar to the Drosophila 'sine oculis' gene product. This gene is found in a cluster of related genes on chromosome 14 and is thought to be involved in eye development. Defects in this gene are a cause of isolated microphthalmia with cataract type 2 (MCOPCT2). [provided by RefSeq, Jul 2008]

GeneCards Summary for SIX6 Gene

SIX6 (SIX Homeobox 6) is a Protein Coding gene. Diseases associated with SIX6 include Optic Disc Anomalies With Retinal And/Or Macular Dystrophy and Microphthalmia. Among its related pathways are Ectoderm Differentiation. Gene Ontology (GO) annotations related to this gene include distal enhancer DNA-binding transcription activator activity, RNA polymerase II-specific. An important paralog of this gene is SIX3.

UniProtKB/Swiss-Prot Summary for SIX6 Gene

Additional gene information for SIX6 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SIX6 Gene

Genomics for SIX6 Gene

GeneHancer (GH) Regulatory Elements for SIX6 Gene

Promoters and enhancers for SIX6 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
GH14J060508 Promoter/Enhancer 1.2 EPDnew Ensembl ENCODE 500.7 -0.1 -71 0.3 REST EZH2 ZNF335 SIN3A RNF2 CHD7 EP300 CTBP2 PKNOX1 SUZ12 SIX6 lnc-SIX1-4 C14orf39
GH14J060510 Enhancer 0.5 Ensembl 500.7 +0.6 555 0.2 EZH2 CBX8 SUZ12 RNF2 CTBP2 POLR2A SIX6 lnc-SIX1-4 C14orf39 ENSG00000258670
GH14J060640 Promoter/Enhancer 2.7 VISTA EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 9.9 +141.0 140998 19.3 FOXK2 CTCF ZSCAN5C SIN3A USF1 POLR2G PHF8 TEAD4 ZFX ZNF639 MIR9718-001 SIX1 TRMT5 C14orf39 SLC38A6 PCNX4 LOC101927702 SIX4 TMEM30B MNAT1
GH14J060485 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas 11.4 -23.4 -23358 1.8 NRF1 ZIC2 ZBTB26 ZNF740 TOE1 MYC RBM25 EZH2 POLR2A NFRKB C14orf39 HSALNG0101709 SIX6 piR-40497-022
GH14J060350 Enhancer 0.8 Ensembl ENCODE dbSUPER 10.7 -158.8 -158845 1 CTCF REST RAD21 TRIM22 SMC3 TAL1 ZNF654 ZNF143 SIX6 piR-38352-174 piR-55194-135
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SIX6 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SIX6

Top Transcription factor binding sites by QIAGEN in the SIX6 gene promoter:
  • Bach1
  • C/EBPalpha
  • FOXJ2
  • FOXJ2 (long isoform)
  • GCNF
  • GCNF-1
  • GCNF-2
  • HEN1
  • RP58
  • S8

Genomic Locations for SIX6 Gene

Genomic Locations for SIX6 Gene
chr14:60,509,146-60,512,850
(GRCh38/hg38)
Size:
3,705 bases
Orientation:
Plus strand
chr14:60,975,669-60,979,568
(GRCh37/hg19)
Size:
3,900 bases
Orientation:
Plus strand

Genomic View for SIX6 Gene

Genes around SIX6 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SIX6 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SIX6 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SIX6 Gene

Proteins for SIX6 Gene

  • Protein details for SIX6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95475-SIX6_HUMAN
    Recommended name:
    Homeobox protein SIX6
    Protein Accession:
    O95475
    Secondary Accessions:
    • Q6NT42
    • Q9P1X8

    Protein attributes for SIX6 Gene

    Size:
    246 amino acids
    Molecular mass:
    27687 Da
    Quaternary structure:
    • Interacts with TLE4 and TLE5.

neXtProt entry for SIX6 Gene

Post-translational modifications for SIX6 Gene

  • Ubiquitination at Lys49
  • Modification sites at PhosphoSitePlus

Other Protein References for SIX6 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for SIX6 Gene

Domains & Families for SIX6 Gene

Gene Families for SIX6 Gene

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

Protein Domains for SIX6 Gene

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

Suggested Antigen Peptide Sequences for SIX6 Gene

GenScript: Design optimal peptide antigens:
  • SIX6 protein (Q5M8S8_HUMAN)
  • SIX6 protein (Q6P051_HUMAN)
  • Sine oculis homeobox homolog 6 (SIX6_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O95475

UniProtKB/Swiss-Prot:

SIX6_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 SIX6: view

Function for SIX6 Gene

Molecular function for SIX6 Gene

UniProtKB/Swiss-Prot Function:
May be involved in eye development.
GENATLAS Biochemistry:
Drosophila sine oculis homolog SIX6 homeo box encoding gene,expressed in the developing and adult retina and in the hypohypothalamic and hypopituitary region

Phenotypes From GWAS Catalog for SIX6 Gene

Gene Ontology (GO) - Molecular Function for SIX6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000976 transcription regulatory region sequence-specific DNA binding IBA 21873635
GO:0000980 RNA polymerase II distal enhancer sequence-specific DNA binding IEA,IDA 18836447
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific NAS 19274049
GO:0003677 DNA binding IEA --
genes like me logo Genes that share ontologies with SIX6: view
genes like me logo Genes that share phenotypes with SIX6: view

Human Phenotype Ontology for SIX6 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SIX6 Gene

MGI Knock Outs for SIX6:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SIX6

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for SIX6 Gene

Localization for SIX6 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SIX6 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 SIX6 gene
Compartment Confidence
nucleus 4
cytosol 3
extracellular 2
cytoskeleton 2
plasma membrane 1
mitochondrion 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for SIX6 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 SIX6: view

Pathways & Interactions for SIX6 Gene

PathCards logo

SuperPathways for SIX6 Gene

SuperPathway Contained pathways
1 Ectoderm Differentiation
genes like me logo Genes that share pathways with SIX6: view

Pathways by source for SIX6 Gene

1 BioSystems pathway for SIX6 Gene

SIGNOR curated interactions for SIX6 Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for SIX6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001654 eye development IBA 21873635
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006357 regulation of transcription by RNA polymerase II IEA --
GO:0007275 multicellular organism development IEA --
GO:0007601 visual perception TAS 10512683
genes like me logo Genes that share ontologies with SIX6: view

Drugs & Compounds for SIX6 Gene

No Compound Related Data Available

Transcripts for SIX6 Gene

mRNA/cDNA for SIX6 Gene

1 REFSEQ mRNAs :
5 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 SIX6

Alternative Splicing Database (ASD) splice patterns (SP) for SIX6 Gene

No ASD Table

Relevant External Links for SIX6 Gene

GeneLoc Exon Structure for
SIX6

Expression for SIX6 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SIX6 Gene

mRNA differential expression in normal tissues according to GTEx for SIX6 Gene

This gene is overexpressed in Pituitary (x48.4).

Protein differential expression in normal tissues from HIPED for SIX6 Gene

This gene is overexpressed in Retina (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for SIX6 Gene



Protein tissue co-expression partners for SIX6 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SIX6

SOURCE GeneReport for Unigene cluster for SIX6 Gene:

Hs.194756

mRNA Expression by UniProt/SwissProt for SIX6 Gene:

O95475-SIX6_HUMAN
Tissue specificity: Expressed in the developing and adult retina. Also expressed in the hypothalamic and the pituitary regions.

Evidence on tissue expression from TISSUES for SIX6 Gene

  • Eye(4.5)
  • Nervous system(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SIX6 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • endocrine
  • integumentary
  • nervous
  • reproductive
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • chin
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • inner ear
  • jaw
  • lip
  • mandible
  • maxilla
  • middle ear
  • mouth
  • nose
  • outer ear
  • pituitary gland
  • skull
Pelvis:
  • testicle
  • urinary bladder
General:
  • peripheral nervous system
  • skin
genes like me logo Genes that share expression patterns with SIX6: view

Orthologs for SIX6 Gene

This gene was present in the common ancestor of animals.

Orthologs for SIX6 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SIX6 30
  • 99.73 (n)
OPTX2 31
  • 93 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SIX6 31
  • 94 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SIX6 31 30
  • 92.95 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Six6 30
  • 90.51 (n)
mouse
(Mus musculus)
Mammalia Six6 17 31 30
  • 90.11 (n)
cow
(Bos Taurus)
Mammalia SIX6 31
  • 72 (a)
OneToOne
chicken
(Gallus gallus)
Aves SIX6 31 30
  • 84.01 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SIX6 31
  • 85 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia six6 30
  • 77.32 (n)
African clawed frog
(Xenopus laevis)
Amphibia six6-A 30
zebrafish
(Danio rerio)
Actinopterygii six6a 31
  • 91 (a)
OneToMany
six6b 31 30
  • 75.51 (n)
OneToMany
zgc63871 30
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003871 30
  • 67.56 (n)
fruit fly
(Drosophila melanogaster)
Insecta Six4 32
  • 56 (a)
Optix 31 32
  • 34 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea ceh-33 32
  • 52 (a)
ceh-34 32
  • 46 (a)
ceh-35 32
  • 35 (a)
ceh-32 31 32
  • 29 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 42 (a)
OneToMany
Species where no ortholog for SIX6 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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 SIX6 Gene

ENSEMBL:
Gene Tree for SIX6 (if available)
TreeFam:
Gene Tree for SIX6 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SIX6: view image

Paralogs for SIX6 Gene

Paralogs for SIX6 Gene

(7) SIMAP similar genes for SIX6 Gene using alignment to 3 proteins:

  • SIX6_HUMAN
  • Q5M8S8_HUMAN
  • Q6P051_HUMAN
genes like me logo Genes that share paralogs with SIX6: view

Variants for SIX6 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SIX6 Gene

SNP ID Clinical significance and condition Chr 14 pos Variation AA Info Type
637058 Pathogenic: Microcornea; Congenital cataract; Nystagmus; Sclerocornea 60,509,945(+) G/C MISSENSE_VARIANT
637953 Pathogenic: Congenital cataract; Microphthalmia; Sclerocornea; Congenital cornea plana 60,509,167(+) GCCGGCGTGCCTGAGC SPLICE_DONOR_VARIANT,INITIATIOR_CODON_VARIANT
rs104894480 Uncertain Significance: Cataract, microphthalmia and nystagmus. - 60,509,891(+) A/Gp.Thr165Ala MISSENSE_VARIANT
rs1061108 Benign: Anophthalmia - microphthalmia 60,511,353(+) C/G THREE_PRIME_UTR_VARIANT
rs140601427 Uncertain Significance: Anophthalmia - microphthalmia 60,511,147(+) G/C SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for SIX6 Gene

Structural Variations from Database of Genomic Variants (DGV) for SIX6 Gene

Variant ID Type Subtype PubMed ID
nsv564880 CNV gain 21841781
nsv564881 CNV gain 21841781

Variation tolerance for SIX6 Gene

Residual Variation Intolerance Score: 58.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 11.10; 92.23% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SIX6 Gene

Human Gene Mutation Database (HGMD)
SIX6
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SIX6

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SIX6 Gene

Disorders for SIX6 Gene

MalaCards: The human disease database

(18) MalaCards diseases for SIX6 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
optic disc anomalies with retinal and/or macular dystrophy
  • odrmd
microphthalmia
  • microphthalmos
sclerocornea
  • isolated congenital sclerocornea
congenital cornea plana
pathologic nystagmus
  • nystagmus
- elite association - COSMIC cancer census association via MalaCards
Search SIX6 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SIX6_HUMAN
  • Optic disk anomalies with retinal and/or macular dystrophy (ODRMD) [MIM:212550]: An ocular disorder characterized by optic nerve dysplasia, optic disk anomalies, chorioretinal dystrophy and macular atrophy. Some patients have microphthalmia. {ECO:0000269 PubMed:23167593}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for SIX6

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with SIX6: view

No data available for Genatlas for SIX6 Gene

Publications for SIX6 Gene

  1. Absence of SIX6 mutations in microphthalmia, anophthalmia, and coloboma. (PMID: 15505031) Aijaz S … Hanson I (Investigative ophthalmology & visual science 2004) 3 23 41 54
  2. Genomic cloning and characterization of the human homeobox gene SIX6 reveals a cluster of SIX genes in chromosome 14 and associates SIX6 hemizygosity with bilateral anophthalmia and pituitary anomalies. (PMID: 10512683) Gallardo ME … Rodríguez de Córdoba S (Genomics 1999) 2 3 4 54
  3. Mutational screening of 10 genes in Chinese patients with microphthalmia and/or coloboma. (PMID: 20057906) Zhang X … Zhang Q (Molecular vision 2009) 3 41 54
  4. Analysis of the developmental SIX6 homeobox gene in patients with anophthalmia/microphthalmia. (PMID: 15266624) Gallardo ME … Bovolenta P (American journal of medical genetics. Part A 2004) 3 4 54
  5. Six9 (Optx2), a new member of the six gene family of transcription factors, is expressed at early stages of vertebrate ocular and pituitary development. (PMID: 10381575) López-Ríos J … Bovolenta P (Mechanisms of development 1999) 3 4 54

Products for SIX6 Gene

Sources for SIX6 Gene