Human Gene SIX5 (uc002pdb.3) Description and Page Index
  Description: Homo sapiens SIX homeobox 5 (SIX5), mRNA.
RefSeq Summary (NM_175875): 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]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1163655.484181.1, AK074826.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA2155770, SAMEA2155984 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000317578.7/ ENSP00000316842.4 RefSeq Select criteria :: based on single protein-coding transcript ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr19:46,268,043-46,272,497 Size: 4,455 Total Exon Count: 3 Strand: -
Coding Region
   Position: hg19 chr19:46,268,759-46,272,102 Size: 3,344 Coding Exon Count: 3 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsOther NamesGeneReviewsModel InformationMethods
Data last updated: 2013-06-15

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr19:46,268,043-46,272,497)mRNA (may differ from genome)Protein (739 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
OMIMPubMedStanford SOURCETreefamUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Homeobox protein SIX5; AltName: Full=DM locus-associated homeodomain protein; AltName: Full=Sine oculis homeobox homolog 5;
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).
SUBUNIT: Probably binds DNA dimer. Interacts with EYA3, and probably EYA1 and EYA2 (By similarity).
INTERACTION: P54253:ATXN1; NbExp=4; IntAct=EBI-946167, EBI-930964;
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.
DEVELOPMENTAL STAGE: At the begin of fourth week of development detected in cytoplasm of somite cells, and at the end of fourth week is accumulated in the nucleus. Between the sixth and eighth week of development detected in the nucleus of limb bud cells.
DISEASE: Defects in SIX5 are the cause of branchiootorenal syndrome type 2 (BOR2) [MIM:610896]. BOR is an autosomal dominant disorder manifested by various combinations of preauricular pits, branchial fistulae or cysts, lacrimal duct stenosis, hearing loss, structural defects of the outer, middle, or inner ear, and renal dysplasia. Associated defects include asthenic habitus, long narrow facies, constricted palate, deep overbite, and myopia. Hearing loss may be due to mondini type cochlear defect and stapes fixation. Penetrance of BOR syndrome is high, although expressivity can be extremely variable.
SIMILARITY: Belongs to the SIX/Sine oculis homeobox family.
SIMILARITY: Contains 1 homeobox DNA-binding domain.
SEQUENCE CAUTION: Sequence=AAH33204.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing; Sequence=AK074826; Type=Erroneous termination; Positions=721; Note=Translated as Glu;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): SIX5
CDC HuGE Published Literature: SIX5

-  MalaCards Disease Associations
  MalaCards Gene Search: SIX5
Diseases sorted by gene-association score: branchiootorenal syndrome 2* (1229), six5-related branchiootorenal spectrum disorders* (500), branchiootorenal syndrome* (236), branchiootorenal spectrum disorders* (71), myotonic dystrophy (14), branchiootic syndrome (11), lacrimal duct obstruction (9), potter's syndrome (9), branchiooculofacial syndrome (8), myotonic disease (8), fraser syndrome 1 (7), myotonic dystrophy 1 (6), deafness, autosomal dominant 10 (5), renal hypodysplasia/aplasia 1 (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
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-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 29.65 RPKM in Ovary
Total median expression: 529.16 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -153.90395-0.390 Picture PostScript Text
3' UTR -305.43716-0.427 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR017970 - Homeobox_CS
IPR001356 - Homeodomain
IPR009057 - Homeodomain-like

Pfam Domains:
PF00046 - Homeobox domain
PF05920 - Homeobox KN domain
PF16878 - Transcriptional regulator, SIX1, N-terminal SD domain

SCOP Domains:
46689 - Homeodomain-like

ModBase Predicted Comparative 3D Structure on Q8N196
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0003677 DNA binding
GO:0005515 protein binding
GO:0043565 sequence-specific DNA binding

Biological Process:
GO:0002088 lens development in camera-type eye
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0007275 multicellular organism development
GO:0007286 spermatid development
GO:0008285 negative regulation of cell proliferation
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:1902723 negative regulation of skeletal muscle satellite cell proliferation

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm

-  Descriptions from all associated GenBank mRNAs
  LF207541 - JP 2014500723-A/15044: Polycomb-Associated Non-Coding RNAs.
BC084563 - Homo sapiens cDNA clone IMAGE:6278582.
BC033204 - Homo sapiens SIX homeobox 5, mRNA (cDNA clone IMAGE:4876082), complete cds.
AK074826 - Homo sapiens cDNA FLJ90345 fis, clone NT2RP2002974, highly similar to HOMEOBOX PROTEIN SIX5.
LF366959 - JP 2014500723-A/174462: Polycomb-Associated Non-Coding RNAs.
JD216875 - Sequence 197899 from Patent EP1572962.
MA602536 - JP 2018138019-A/174462: Polycomb-Associated Non-Coding RNAs.
MA443118 - JP 2018138019-A/15044: Polycomb-Associated Non-Coding RNAs.
LF366960 - JP 2014500723-A/174463: Polycomb-Associated Non-Coding RNAs.
JD183577 - Sequence 164601 from Patent EP1572962.
JD253578 - Sequence 234602 from Patent EP1572962.
JD177866 - Sequence 158890 from Patent EP1572962.
JD422837 - Sequence 403861 from Patent EP1572962.
JD387030 - Sequence 368054 from Patent EP1572962.
MA602537 - JP 2018138019-A/174463: Polycomb-Associated Non-Coding RNAs.
JD323807 - Sequence 304831 from Patent EP1572962.
JD125286 - Sequence 106310 from Patent EP1572962.
JD222804 - Sequence 203828 from Patent EP1572962.
JD426634 - Sequence 407658 from Patent EP1572962.
JD346227 - Sequence 327251 from Patent EP1572962.
JD375057 - Sequence 356081 from Patent EP1572962.
JD439562 - Sequence 420586 from Patent EP1572962.
JD295038 - Sequence 276062 from Patent EP1572962.
JD132681 - Sequence 113705 from Patent EP1572962.
JD468311 - Sequence 449335 from Patent EP1572962.
BC156208 - Synthetic construct Homo sapiens clone IMAGE:100061576, MGC:190036 SIX homeobox 5 (SIX5) mRNA, encodes complete protein.
BC156983 - Synthetic construct Homo sapiens clone IMAGE:100062823, MGC:190623 SIX homeobox 5 (SIX5) mRNA, encodes complete protein.
AB464211 - Synthetic construct DNA, clone: pF1KB9760, Homo sapiens SIX5 gene for SIX homeobox 5, without stop codon, in Flexi system.
LF212090 - JP 2014500723-A/19593: Polycomb-Associated Non-Coding RNAs.
LF207539 - JP 2014500723-A/15042: Polycomb-Associated Non-Coding RNAs.
LF366953 - JP 2014500723-A/174456: Polycomb-Associated Non-Coding RNAs.
JD310212 - Sequence 291236 from Patent EP1572962.
JD038520 - Sequence 19544 from Patent EP1572962.
JD202911 - Sequence 183935 from Patent EP1572962.
JD039205 - Sequence 20229 from Patent EP1572962.
JD484847 - Sequence 465871 from Patent EP1572962.
LF366952 - JP 2014500723-A/174455: Polycomb-Associated Non-Coding RNAs.
MA602530 - JP 2018138019-A/174456: Polycomb-Associated Non-Coding RNAs.
MA602529 - JP 2018138019-A/174455: Polycomb-Associated Non-Coding RNAs.
MA447667 - JP 2018138019-A/19593: Polycomb-Associated Non-Coding RNAs.
MA443116 - JP 2018138019-A/15042: Polycomb-Associated Non-Coding RNAs.

-  Other Names for This Gene
  Alternate Gene Symbols: DMAHP, NM_175875, NP_787071, Q8N196, SIX5_HUMAN
UCSC ID: uc002pdb.3
RefSeq Accession: NM_175875
Protein: Q8N196 (aka SIX5_HUMAN)
CCDS: CCDS12673.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene SIX5:
bor (Branchiootorenal Spectrum Disorder)

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_175875.4
exon count: 3CDS single in 3' UTR: no RNA size: 3352
ORF size: 2220CDS single in intron: no Alignment % ID: 99.97
txCdsPredict score: 4619.00frame shift in genome: no % Coverage: 99.37
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.