Details for: SIX3

Gene ID: 6496

Symbol: SIX3

Ensembl ID: ENSG00000138083

Description: SIX homeobox 3

Associated with

Cells (max top 100)

(Cell Significance Index and respective Thresholds are uniquely calculated using our advanced thresholding algorithms to reveal cell-specific gene markers)

  • Cell Name: hematopoietic oligopotent progenitor cell (CL0002032)
    Fold Change: 87.9187
    Cell Significance Index: -22.3000
  • Cell Name: cone retinal bipolar cell (CL0000752)
    Fold Change: 8.0009
    Cell Significance Index: 61.6700
  • Cell Name: glycinergic neuron (CL1001509)
    Fold Change: 5.2236
    Cell Significance Index: 274.2600
  • Cell Name: CD8-positive, alpha-beta regulatory T cell (CL0000795)
    Fold Change: 4.5125
    Cell Significance Index: -13.8600
  • Cell Name: photoreceptor cell (CL0000210)
    Fold Change: 3.3179
    Cell Significance Index: 46.6000
  • Cell Name: retinal progenitor cell (CL0002672)
    Fold Change: 2.0912
    Cell Significance Index: 117.3500
  • Cell Name: GABAergic amacrine cell (CL4030027)
    Fold Change: 1.7766
    Cell Significance Index: 22.0400
  • Cell Name: retinal bipolar neuron (CL0000748)
    Fold Change: 1.2886
    Cell Significance Index: 15.6200
  • Cell Name: OFF-bipolar cell (CL0000750)
    Fold Change: 1.1741
    Cell Significance Index: 10.3400
  • Cell Name: pigmented ciliary epithelial cell (CL0002303)
    Fold Change: 0.8820
    Cell Significance Index: 128.2100
  • Cell Name: eye photoreceptor cell (CL0000287)
    Fold Change: 0.4681
    Cell Significance Index: 29.5000
  • Cell Name: indirect pathway medium spiny neuron (CL4023029)
    Fold Change: 0.3520
    Cell Significance Index: 15.5700
  • Cell Name: direct pathway medium spiny neuron (CL4023026)
    Fold Change: 0.2294
    Cell Significance Index: 8.6900
  • Cell Name: lens epithelial cell (CL0002224)
    Fold Change: 0.1666
    Cell Significance Index: 256.4700
  • Cell Name: kidney epithelial cell (CL0002518)
    Fold Change: 0.1604
    Cell Significance Index: 4.7300
  • Cell Name: secondary lens fiber (CL0002225)
    Fold Change: 0.1415
    Cell Significance Index: 192.4200
  • Cell Name: CD14-positive, CD16-negative classical monocyte (CL0002057)
    Fold Change: 0.1342
    Cell Significance Index: 2.4800
  • Cell Name: anterior lens cell (CL0002223)
    Fold Change: 0.1007
    Cell Significance Index: 185.7000
  • Cell Name: non-pigmented ciliary epithelial cell (CL0002304)
    Fold Change: 0.0984
    Cell Significance Index: 62.5200
  • Cell Name: ON-bipolar cell (CL0000749)
    Fold Change: 0.0505
    Cell Significance Index: 0.5700
  • Cell Name: pigmented epithelial cell (CL0000529)
    Fold Change: 0.0457
    Cell Significance Index: 86.1400
  • Cell Name: retinal ganglion cell (CL0000740)
    Fold Change: 0.0424
    Cell Significance Index: 0.3500
  • Cell Name: Mueller cell (CL0000636)
    Fold Change: 0.0364
    Cell Significance Index: 0.2800
  • Cell Name: pancreatic PP cell (CL0002275)
    Fold Change: 0.0331
    Cell Significance Index: 20.6700
  • Cell Name: type B pancreatic cell (CL0000169)
    Fold Change: 0.0045
    Cell Significance Index: 2.5400
  • Cell Name: pancreatic A cell (CL0000171)
    Fold Change: -0.0073
    Cell Significance Index: -5.4100
  • Cell Name: GABAergic interneuron (CL0011005)
    Fold Change: -0.0200
    Cell Significance Index: -13.8500
  • Cell Name: kidney loop of Henle cortical thick ascending limb epithelial cell (CL1001109)
    Fold Change: -0.0213
    Cell Significance Index: -15.6100
  • Cell Name: fallopian tube secretory epithelial cell (CL4030006)
    Fold Change: -0.0233
    Cell Significance Index: -0.3600
  • Cell Name: pancreatic acinar cell (CL0002064)
    Fold Change: -0.0302
    Cell Significance Index: -5.1600
  • Cell Name: pancreatic ductal cell (CL0002079)
    Fold Change: -0.0317
    Cell Significance Index: -3.6300
  • Cell Name: pancreatic D cell (CL0000173)
    Fold Change: -0.0384
    Cell Significance Index: -8.0800
  • Cell Name: cell in vitro (CL0001034)
    Fold Change: -0.0395
    Cell Significance Index: -21.5600
  • Cell Name: ciliary muscle cell (CL1000443)
    Fold Change: -0.0413
    Cell Significance Index: -18.7600
  • Cell Name: dopaminergic neuron (CL0000700)
    Fold Change: -0.0482
    Cell Significance Index: -13.8600
  • Cell Name: keratinocyte (CL0000312)
    Fold Change: -0.0626
    Cell Significance Index: -1.5600
  • Cell Name: obsolete caudal ganglionic eminence derived GABAergic cortical interneuron (CL4023070)
    Fold Change: -0.0652
    Cell Significance Index: -23.3800
  • Cell Name: intermediate cell of urothelium (CL4030055)
    Fold Change: -0.0779
    Cell Significance Index: -14.0400
  • Cell Name: CD4-positive, alpha-beta thymocyte (CL0000810)
    Fold Change: -0.0847
    Cell Significance Index: -1.4600
  • Cell Name: cerebral cortex endothelial cell (CL1001602)
    Fold Change: -0.1159
    Cell Significance Index: -2.3600
  • Cell Name: basal cell of urothelium (CL1000486)
    Fold Change: -0.1226
    Cell Significance Index: -15.0700
  • Cell Name: CD14-low, CD16-positive monocyte (CL0002396)
    Fold Change: -0.1312
    Cell Significance Index: -3.1800
  • Cell Name: smooth muscle cell of prostate (CL1000487)
    Fold Change: -0.1331
    Cell Significance Index: -1.5400
  • Cell Name: L2/3-6 intratelencephalic projecting glutamatergic neuron (CL4023040)
    Fold Change: -0.1346
    Cell Significance Index: -27.0100
  • Cell Name: cerebral cortex GABAergic interneuron (CL0010011)
    Fold Change: -0.1469
    Cell Significance Index: -1.4800
  • Cell Name: lactocyte (CL0002325)
    Fold Change: -0.1475
    Cell Significance Index: -19.0500
  • Cell Name: stromal cell of ovary (CL0002132)
    Fold Change: -0.1580
    Cell Significance Index: -21.7000
  • Cell Name: abnormal cell (CL0001061)
    Fold Change: -0.1604
    Cell Significance Index: -16.3800
  • Cell Name: skeletal muscle fibroblast (CL0011027)
    Fold Change: -0.1737
    Cell Significance Index: -1.1800
  • Cell Name: pancreatic endocrine cell (CL0008024)
    Fold Change: -0.1898
    Cell Significance Index: -21.6700
  • Cell Name: smooth muscle cell of sphincter of pupil (CL0002243)
    Fold Change: -0.1955
    Cell Significance Index: -20.3600
  • Cell Name: kidney loop of Henle descending limb epithelial cell (CL1001021)
    Fold Change: -0.1971
    Cell Significance Index: -15.6100
  • Cell Name: prostate gland microvascular endothelial cell (CL2000059)
    Fold Change: -0.2061
    Cell Significance Index: -1.4800
  • Cell Name: epithelial cell of urethra (CL1000296)
    Fold Change: -0.2278
    Cell Significance Index: -1.4100
  • Cell Name: endothelial cell of venule (CL1000414)
    Fold Change: -0.2616
    Cell Significance Index: -2.9700
  • Cell Name: progenitor cell of mammary luminal epithelium (CL0009116)
    Fold Change: -0.2657
    Cell Significance Index: -19.8000
  • Cell Name: early pro-B cell (CL0002046)
    Fold Change: -0.2751
    Cell Significance Index: -17.7500
  • Cell Name: forebrain neuroblast (CL1000042)
    Fold Change: -0.2835
    Cell Significance Index: -17.4300
  • Cell Name: epithelial cell of nephron (CL1000449)
    Fold Change: -0.2918
    Cell Significance Index: -2.4800
  • Cell Name: midget ganglion cell of retina (CL4023188)
    Fold Change: -0.2947
    Cell Significance Index: -3.0700
  • Cell Name: macroglial cell (CL0000126)
    Fold Change: -0.3006
    Cell Significance Index: -3.4800
  • Cell Name: luminal adaptive secretory precursor cell of mammary gland (CL4033057)
    Fold Change: -0.3765
    Cell Significance Index: -17.7000
  • Cell Name: hippocampal granule cell (CL0001033)
    Fold Change: -0.3883
    Cell Significance Index: -26.1100
  • Cell Name: retinal pigment epithelial cell (CL0002586)
    Fold Change: -0.4184
    Cell Significance Index: -4.5000
  • Cell Name: ganglion interneuron (CL0000397)
    Fold Change: -0.4611
    Cell Significance Index: -3.7800
  • Cell Name: enterocyte of epithelium of large intestine (CL0002071)
    Fold Change: -0.5577
    Cell Significance Index: -25.2800
  • Cell Name: bladder urothelial cell (CL1001428)
    Fold Change: -0.5791
    Cell Significance Index: -30.0900
  • Cell Name: amacrine cell (CL0000561)
    Fold Change: -0.5821
    Cell Significance Index: -7.2900
  • Cell Name: fibroblast of mammary gland (CL0002555)
    Fold Change: -0.5847
    Cell Significance Index: -16.7600
  • Cell Name: neural cell (CL0002319)
    Fold Change: -0.6094
    Cell Significance Index: -7.1100
  • Cell Name: glycinergic amacrine cell (CL4030028)
    Fold Change: -0.6279
    Cell Significance Index: -6.7500
  • Cell Name: CD4-positive, alpha-beta memory T cell, CD45RO-positive (CL0001204)
    Fold Change: -0.6341
    Cell Significance Index: -18.6200
  • Cell Name: stratified epithelial cell (CL0000079)
    Fold Change: -0.6463
    Cell Significance Index: -23.7300
  • Cell Name: acinar cell of salivary gland (CL0002623)
    Fold Change: -0.6473
    Cell Significance Index: -30.1800
  • Cell Name: megakaryocyte (CL0000556)
    Fold Change: -0.6619
    Cell Significance Index: -10.7200
  • Cell Name: lens fiber cell (CL0011004)
    Fold Change: -0.6836
    Cell Significance Index: -21.6200
  • Cell Name: cytotoxic T cell (CL0000910)
    Fold Change: -0.6940
    Cell Significance Index: -10.1200
  • Cell Name: small intestine goblet cell (CL1000495)
    Fold Change: -0.7274
    Cell Significance Index: -25.5600
  • Cell Name: basal cell of prostate epithelium (CL0002341)
    Fold Change: -0.7351
    Cell Significance Index: -20.0100
  • Cell Name: L5 extratelencephalic projecting glutamatergic cortical neuron (CL4023041)
    Fold Change: -0.7465
    Cell Significance Index: -26.1500
  • Cell Name: pro-T cell (CL0000827)
    Fold Change: -0.8353
    Cell Significance Index: -21.3400
  • Cell Name: L6b glutamatergic cortical neuron (CL4023038)
    Fold Change: -0.8366
    Cell Significance Index: -27.3900
  • Cell Name: corticothalamic-projecting glutamatergic cortical neuron (CL4023013)
    Fold Change: -0.8377
    Cell Significance Index: -26.6800
  • Cell Name: erythrocyte (CL0000232)
    Fold Change: -0.8456
    Cell Significance Index: -21.5500
  • Cell Name: retinal rod cell (CL0000604)
    Fold Change: -0.8473
    Cell Significance Index: -10.1000
  • Cell Name: hippocampal pyramidal neuron (CL1001571)
    Fold Change: -0.8477
    Cell Significance Index: -24.1900
  • Cell Name: tracheal goblet cell (CL1000329)
    Fold Change: -0.8486
    Cell Significance Index: -7.0200
  • Cell Name: ependymal cell (CL0000065)
    Fold Change: -0.8499
    Cell Significance Index: -10.0200
  • Cell Name: monocyte (CL0000576)
    Fold Change: -0.8517
    Cell Significance Index: -9.8000
  • Cell Name: Purkinje cell (CL0000121)
    Fold Change: -0.8523
    Cell Significance Index: -18.6600
  • Cell Name: nasal mucosa goblet cell (CL0002480)
    Fold Change: -0.8667
    Cell Significance Index: -8.8400
  • Cell Name: cortical interneuron (CL0008031)
    Fold Change: -0.8836
    Cell Significance Index: -21.1900
  • Cell Name: microcirculation associated smooth muscle cell (CL0008035)
    Fold Change: -0.8869
    Cell Significance Index: -7.4500
  • Cell Name: placental villous trophoblast (CL2000060)
    Fold Change: -0.8949
    Cell Significance Index: -23.9000
  • Cell Name: mesenchymal cell (CL0008019)
    Fold Change: -0.9055
    Cell Significance Index: -15.1600
  • Cell Name: hematopoietic stem cell (CL0000037)
    Fold Change: -0.9126
    Cell Significance Index: -15.6000
  • Cell Name: CD14-positive monocyte (CL0001054)
    Fold Change: -0.9342
    Cell Significance Index: -18.2700
  • Cell Name: cortical cell of adrenal gland (CL0002097)
    Fold Change: -0.9382
    Cell Significance Index: -25.1400
  • Cell Name: neuron (CL0000540)
    Fold Change: -0.9410
    Cell Significance Index: -8.9200
  • Cell Name: obsolete epithelial cell of alveolus of lung (CL0010003)
    Fold Change: -0.9590
    Cell Significance Index: -23.9200

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Other Information

**Key Characteristics:** 1. **Transcriptional regulation:** SIX3 acts as a transcriptional activator, regulating the expression of target genes involved in developmental processes. 2. **Cell-type specificity:** SIX3 is specifically expressed in various cell types, including tracheal goblet cells, glycinergic neurons, and lens epithelial cells, suggesting its role in tissue-specific differentiation. 3. **Developmental stage:** SIX3 expression is tightly regulated during different developmental stages, from embryogenesis to adulthood, indicating its involvement in various developmental processes. 4. **Cancer association:** SIX3 has been implicated in several cancers, including breast, lung, and colon cancer, suggesting its potential role as a tumor suppressor. **Pathways and Functions:** 1. **Apoptotic process involved in development:** SIX3 regulates the expression of pro-apoptotic genes, influencing the timing and extent of cell death during development. 2. **Brain development:** SIX3 is involved in the regulation of neural cell proliferation, differentiation, and migration, shaping the structure and function of the brain. 3. **Eye development:** SIX3 plays a crucial role in the formation of the lens, retina, and optic nerve, highlighting its importance in visual development. 4. **Cell proliferation and differentiation:** SIX3 regulates the expression of genes involved in cell cycle progression, differentiation, and survival, influencing tissue homeostasis. **Clinical Significance:** 1. **Neurological disorders:** SIX3 dysregulation has been implicated in various neurological disorders, including autism, schizophrenia, and Alzheimer's disease, suggesting its potential role in neural development and function. 2. **Cancer:** SIX3's tumor suppressor function has been proposed, with its expression reduced in several types of cancer, including breast, lung, and colon cancer. 3. **Eye disorders:** SIX3 mutations have been associated with eye disorders, including congenital cataracts and anophthalmia, highlighting its importance in ocular development. 4. **Regulatory potential:** SIX3's ability to regulate gene expression makes it a potential therapeutic target for various diseases, including cancer and neurological disorders. In conclusion, the SIX3 gene plays a critical role in regulating developmental processes, neural cell fate determination, and tissue homeostasis. Its dysregulation has been implicated in various diseases, highlighting the importance of this gene in maintaining human health and disease prevention. Further research is necessary to fully elucidate the mechanisms by which SIX3 regulates gene expression and its potential therapeutic applications.

Genular Protein ID: 1435548606

Symbol: SIX3_HUMAN

Name: Homeobox protein SIX3

UniProtKB Accession Codes:

O95343 D6W5A5 Q53T42

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 1 GO 34 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 5 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 7 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9889003

Title: Genomic cloning, structure, expression pattern, and chromosomal location of the human SIX3 gene.

PubMed ID: 9889003

DOI: 10.1006/geno.1998.5611

PubMed ID: 10415461

Title: Sequence and location of SIX3, a homeobox gene expressed in the human eye.

PubMed ID: 10415461

DOI: 10.1076/opge.20.1.7.2298

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

PubMed ID: 12543801

Title: The homeotic protein Six3 is a coactivator of the nuclear receptor NOR-1 and a corepressor of the fusion protein EWS/NOR-1 in human extraskeletal myxoid chondrosarcomas.

PubMed ID: 12543801

PubMed ID: 12441302

Title: Six3 and Six6 activity is modulated by members of the groucho family.

PubMed ID: 12441302

DOI: 10.1242/dev.00185

PubMed ID: 15523651

Title: Functional characterization of SIX3 homeodomain mutations in holoprosencephaly: interaction with the nuclear receptor NR4A3/NOR1.

PubMed ID: 15523651

DOI: 10.1002/humu.20102

PubMed ID: 14973488

Title: Direct interaction of geminin and Six3 in eye development.

PubMed ID: 14973488

DOI: 10.1038/nature02292

PubMed ID: 18775421

Title: Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development.

PubMed ID: 18775421

DOI: 10.1016/j.ydbio.2008.08.008

PubMed ID: 18791198

Title: Mutations in the human SIX3 gene in holoprosencephaly are loss of function.

PubMed ID: 18791198

DOI: 10.1093/hmg/ddn294

PubMed ID: 10369266

Title: Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly.

PubMed ID: 10369266

DOI: 10.1038/9718

PubMed ID: 15221788

Title: Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: mutation review and genotype-phenotype correlations.

PubMed ID: 15221788

DOI: 10.1002/humu.20056

PubMed ID: 17001667

Title: SIX3 mutations with holoprosencephaly.

PubMed ID: 17001667

DOI: 10.1002/ajmg.a.31377

PubMed ID: 20531442

Title: The unfolding clinical spectrum of holoprosencephaly due to mutations in SHH, ZIC2, SIX3 and TGIF genes.

PubMed ID: 20531442

DOI: 10.1038/ejhg.2010.70

PubMed ID: 20157829

Title: Heterozygous mutations in SIX3 and SHH are associated with schizencephaly and further expand the clinical spectrum of holoprosencephaly.

PubMed ID: 20157829

DOI: 10.1007/s00439-010-0797-4

Sequence Information:

  • Length: 332
  • Mass: 35487
  • Checksum: 21EA07F6A2DD978F
  • Sequence:
    • MVFRSPLDLY SSHFLLPNFA DSHHRSILLA SSGGGNGAGG GGGAGGGSGG GNGAGGGGAG 
GAGGGGGGGS RAPPEELSMF QLPTLNFSPE QVASVCETLE ETGDIERLGR FLWSLPVAPG 
ACEAINKHES ILRARAVVAF HTGNFRDLYH ILENHKFTKE SHGKLQAMWL EAHYQEAEKL 
RGRPLGPVDK YRVRKKFPLP RTIWDGEQKT HCFKERTRSL LREWYLQDPY PNPSKKRELA 
QATGLTPTQV GNWFKNRRQR DRAAAAKNRL QHQAIGPSGM RSLAEPGCPT HGSAESPSTA 
ASPTTSVSSL TERADTGTSI LSVTSSDSEC DV

Database document:

This is a preview of the gene's schema. Only a few entries are kept for 'singleCellExpressions,' 'mRNAExpressions,' and other large data arrays for visualization purposes. You can zoom in with the mouse wheel for a closer view, and the text will adjust automatically if necessary. For the full schema, download it here.