The protein encoded by this gene is a homeodomain-containing transcription factor that appears to function in the regulation of organogenesis. This gene is located downstream of the dystrophia myotonica-protein kinase gene. Mutations in this gene are a cause of branchiootorenal syndrome type 2. [provided by RefSeq, Jul 2009] See more...

Aliases for SIX5 Gene

Aliases for SIX5 Gene

  • SIX Homeobox 5 2 3 5
  • DM Locus-Associated Homeodomain Protein 3 4
  • Sine Oculis Homeobox Homolog 5 3 4
  • Homeobox Protein SIX5 3 4
  • DMAHP 3 4
  • Dystrophia Myotonica-Associated Homeodomain Protein 3
  • Sine Oculis Homeobox (Drosophila) Homolog 5 2
  • Sine Oculis Homeobox Homolog 5 (Drosophila) 2
  • BOR2 3
  • SIX5 5

External Ids for SIX5 Gene

Previous HGNC Symbols for SIX5 Gene

  • DMAHP

Previous GeneCards Identifiers for SIX5 Gene

  • GC19U990028
  • GC19M050959
  • GC19M046268
  • GC19M042696

Summaries for SIX5 Gene

Entrez Gene Summary for SIX5 Gene

  • The protein encoded by this gene is a homeodomain-containing transcription factor that appears to function in the regulation of organogenesis. This gene is located downstream of the dystrophia myotonica-protein kinase gene. Mutations in this gene are a cause of branchiootorenal syndrome type 2. [provided by RefSeq, Jul 2009]

GeneCards Summary for SIX5 Gene

SIX5 (SIX Homeobox 5) is a Protein Coding gene. Diseases associated with SIX5 include Branchiootorenal Syndrome 2 and Branchiootorenal Syndrome. Gene Ontology (GO) annotations related to this gene include sequence-specific DNA binding. An important paralog of this gene is SIX4.

UniProtKB/Swiss-Prot Summary for SIX5 Gene

  • Transcription factor that is thought to be involved in regulation of organogenesis. May be involved in determination and maintenance of retina formation. Binds a 5'-GGTGTCAG-3' motif present in the ARE regulatory element of ATP1A1. Binds a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the myogenin promoter, and in the IGFBP5 promoter (By similarity). Thought to be regulated by association with Dach and Eya proteins, and seems to be coactivated by EYA1, EYA2 and EYA3 (By similarity).

Gene Wiki entry for SIX5 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SIX5 Gene

Genomics for SIX5 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SIX5 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SIX5 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SIX5

Top Transcription factor binding sites by QIAGEN in the SIX5 gene promoter:
  • AREB6
  • CUTL1
  • ITF-2
  • Nkx2-5
  • Roaz
  • RSRFC4
  • Sp1
  • SRF
  • SRF (504 AA)
  • Tal-1beta

Genomic Locations for SIX5 Gene

Genomic Locations for SIX5 Gene
chr19:45,764,785-45,769,252
(GRCh38/hg38)
Size:
4,468 bases
Orientation:
Minus strand
chr19:46,268,043-46,272,497
(GRCh37/hg19)
Size:
4,455 bases
Orientation:
Minus strand

Genomic View for SIX5 Gene

Genes around SIX5 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SIX5 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SIX5 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SIX5 Gene

Proteins for SIX5 Gene

  • Protein details for SIX5 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8N196-SIX5_HUMAN
    Recommended name:
    Homeobox protein SIX5
    Protein Accession:
    Q8N196

    Protein attributes for SIX5 Gene

    Size:
    739 amino acids
    Molecular mass:
    74562 Da
    Quaternary structure:
    • Probably binds DNA dimer. Interacts with EYA3, and probably EYA1 and EYA2 (By similarity).
    SequenceCaution:
    • Sequence=AAH33204.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305}; Sequence=AK074826; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};

neXtProt entry for SIX5 Gene

Post-translational modifications for SIX5 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SIX5 Gene

No data available for DME Specific Peptides for SIX5 Gene

Domains & Families for SIX5 Gene

Gene Families for SIX5 Gene

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

Protein Domains for SIX5 Gene

Suggested Antigen Peptide Sequences for SIX5 Gene

GenScript: Design optimal peptide antigens:
  • Sine oculis homeobox homolog 5 (SIX5_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8N196

UniProtKB/Swiss-Prot:

SIX5_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 SIX5: view

Function for SIX5 Gene

Molecular function for SIX5 Gene

UniProtKB/Swiss-Prot Function:
Transcription factor that is thought to be involved in regulation of organogenesis. May be involved in determination and maintenance of retina formation. Binds a 5'-GGTGTCAG-3' motif present in the ARE regulatory element of ATP1A1. Binds a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the myogenin promoter, and in the IGFBP5 promoter (By similarity). Thought to be regulated by association with Dach and Eya proteins, and seems to be coactivated by EYA1, EYA2 and EYA3 (By similarity).
GENATLAS Biochemistry:
Drosophila sine oculis homolog SIX5,myotonic dystrophy (DM) locus-associated homeo box encoding gene,expressed in skeletal muscle,heart and brain,also expressed in eye,especially in lens epithelium,potentially involved in the development of adult onset cataracts frequently observed in DM,homolog to the muscle-specific transcription factor AREC3,inhibited in dystrophia myotonica by CTG repeat expansion in 3'-non-coding region of DMPK,abuting its own 5'end

Phenotypes From GWAS Catalog for SIX5 Gene

Gene Ontology (GO) - Molecular Function for SIX5 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 ISM 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 SIX5: view
genes like me logo Genes that share phenotypes with SIX5: view

Human Phenotype Ontology for SIX5 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SIX5 Gene

MGI Knock Outs for SIX5:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SIX5

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for SIX5 Gene

Localization for SIX5 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SIX5 Gene

Cytoplasm. Nucleus.

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 SIX5 gene
Compartment Confidence
nucleus 5
cytosol 3
extracellular 2
golgi apparatus 2
plasma membrane 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1

Gene Ontology (GO) - Cellular Components for SIX5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin ISA --
GO:0005634 nucleus IEA,IBA 21873635
GO:0005667 transcription factor complex IBA 21873635
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with SIX5: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for SIX5 Gene

Pathways & Interactions for SIX5 Gene

PathCards logo

SuperPathways for SIX5 Gene

No Data Available

Gene Ontology (GO) - Biological Process for SIX5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002088 lens development in camera-type eye IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0007275 multicellular organism development IEA --
GO:0007286 spermatid development IEA --
GO:0008285 negative regulation of cell proliferation IEA --
genes like me logo Genes that share ontologies with SIX5: view

No data available for Pathways by source and SIGNOR curated interactions for SIX5 Gene

Drugs & Compounds for SIX5 Gene

No Compound Related Data Available

Transcripts for SIX5 Gene

mRNA/cDNA for SIX5 Gene

1 REFSEQ mRNAs :
5 NCBI additional mRNA sequence :
4 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 SIX5

Alternative Splicing Database (ASD) splice patterns (SP) for SIX5 Gene

ExUns: 1a · 1b ^ 2 ^ 3a · 3b
SP1:
SP2: -

Relevant External Links for SIX5 Gene

GeneLoc Exon Structure for
SIX5

Expression for SIX5 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SIX5 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for SIX5 Gene

This gene is overexpressed in Heart (48.5), Peripheral blood mononuclear cells (10.7), and Brain (8.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SIX5 Gene



Protein tissue co-expression partners for SIX5 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SIX5

SOURCE GeneReport for Unigene cluster for SIX5 Gene:

Hs.43314

mRNA Expression by UniProt/SwissProt for SIX5 Gene:

Q8N196-SIX5_HUMAN
Tissue specificity: Expressed in adult but not in fetal eyes. Found in corneal epithelium and endothelium, lens epithelium, ciliary body epithelia, cellular layers of the retina and the sclera.

Evidence on tissue expression from TISSUES for SIX5 Gene

  • Eye(4.6)
  • Heart(3.3)
  • Blood(2.9)
  • Kidney(2.8)
  • Nervous system(2.8)
  • Liver(2.8)
  • Intestine(2.6)
  • Lung(2.4)
  • Pancreas(2.4)
  • Skin(2.2)
  • Adrenal gland(2.1)
  • Muscle(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SIX5 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • endocrine
  • immune
  • integumentary
  • nervous
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cheek
  • chin
  • cranial nerve
  • ear
  • face
  • head
  • inner ear
  • jaw
  • lacrimal apparatus
  • mandible
  • maxilla
  • middle ear
  • mouth
  • neck
  • nose
  • outer ear
  • pharynx
  • skull
  • thyroid
  • tongue
  • tooth
Thorax:
  • esophagus
Abdomen:
  • biliary tract
  • duodenum
  • intestine
  • kidney
  • large intestine
  • pancreas
  • small intestine
  • stomach
Pelvis:
  • pelvis
  • ureter
  • urinary bladder
Limb:
  • femur
  • hip
  • lower limb
  • thigh
General:
  • peripheral nerve
  • peripheral nervous system
  • skin
genes like me logo Genes that share expression patterns with SIX5: view

No data available for mRNA differential expression in normal tissues for SIX5 Gene

Orthologs for SIX5 Gene

This gene was present in the common ancestor of animals.

Orthologs for SIX5 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SIX5 30 31
  • 99.53 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia SIX5 30 31
  • 88.79 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia SIX5 30 31
  • 88.5 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia SIX5 31
  • 86 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Six5 30 17 31
  • 84.19 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Six5 30
  • 83.96 (n)
Lizard
(Anolis carolinensis)
Reptilia -- 31
  • 39 (a)
ManyToMany
Zebrafish
(Danio rerio)
Actinopterygii six4.3 31
  • 32 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Six4 31
  • 33 (a)
OneToMany
Species where no ortholog for SIX5 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • Chicken (Gallus gallus)
  • 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)
  • Oppossum (Monodelphis domestica)
  • 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 Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • 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)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for SIX5 Gene

ENSEMBL:
Gene Tree for SIX5 (if available)
TreeFam:
Gene Tree for SIX5 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SIX5: view image

Paralogs for SIX5 Gene

Paralogs for SIX5 Gene

(6) SIMAP similar genes for SIX5 Gene using alignment to 3 proteins:

  • SIX5_HUMAN
  • H0YLF6_HUMAN
  • H0YLK1_HUMAN
genes like me logo Genes that share paralogs with SIX5: view

Variants for SIX5 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SIX5 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
636531 Uncertain Significance: not provided 45,766,618(-) AGCAGGCACT/A INFRAME_DELETION
668435 Benign/Likely Benign: not provided 45,766,917(-) G/A SYNONYMOUS_VARIANT
676044 Likely Benign: not provided 45,768,817(-) C/T MISSENSE_VARIANT
680210 Likely Benign: not provided 45,768,879(-) C/G FIVE_PRIME_UTR_VARIANT
681903 Likely Benign: not provided 45,768,352(-) G/A SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for SIX5 Gene

Structural Variations from Database of Genomic Variants (DGV) for SIX5 Gene

Variant ID Type Subtype PubMed ID
nsv579870 CNV loss 21841781

Variation tolerance for SIX5 Gene

Gene Damage Index Score: 8.76; 86.70% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SIX5 Gene

Human Gene Mutation Database (HGMD)
SIX5
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SIX5

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SIX5 Gene

Disorders for SIX5 Gene

MalaCards: The human disease database

(14) MalaCards diseases for SIX5 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
branchiootorenal syndrome 2
  • bor2
branchiootorenal syndrome
  • branchiootorenal dysplasia
myotonic dystrophy
  • myotonic dystrophy 1
branchiootorenal spectrum disorder
branchiootic syndrome
  • branchiootic syndrome 1
- elite association - COSMIC cancer census association via MalaCards
Search SIX5 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SIX5_HUMAN
  • Branchiootorenal syndrome 2 (BOR2) [MIM:610896]: A syndrome characterized by branchial cleft fistulas or cysts, sensorineural and/or conductive hearing loss, pre-auricular pits, structural defects of the outer, middle or inner ear, and renal malformations. {ECO:0000269 PubMed:17357085}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for SIX5

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with SIX5: view

No data available for Genatlas for SIX5 Gene

Publications for SIX5 Gene

  1. A novel homeodomain-encoding gene is associated with a large CpG island interrupted by the myotonic dystrophy unstable (CTG)n repeat. (PMID: 8595416) Boucher CA … Chartier FL (Human molecular genetics 1995) 2 3 4 23
  2. Transcription factor SIX5 is mutated in patients with branchio-oto-renal syndrome. (PMID: 17357085) Hoskins BE … Hildebrandt F (American journal of human genetics 2007) 3 4 23
  3. Six and Eya expression during human somitogenesis and MyoD gene family activation. (PMID: 12500905) Fougerousse F … Maire P (Journal of muscle research and cell motility 2002) 3 4 23
  4. Characterization of the expression of DMPK and SIX5 in the human eye and implications for pathogenesis in myotonic dystrophy. (PMID: 9949207) Winchester CL … Johnson KJ (Human molecular genetics 1999) 3 4 23
  5. Association of genetic variants with hemorrhagic stroke in Japanese individuals. (PMID: 20198315) Yoshida T … Yamada Y (International journal of molecular medicine 2010) 3 41

Products for SIX5 Gene

Sources for SIX5 Gene