Details for: TSHZ3

Gene ID: 57616

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: TSHZ3

Ensembl ID: ENSG00000121297

Description: teashirt zinc finger homeobox 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • sst GABAergic cortical interneuron CL4023017
    CSI 32.37
    rCSI 41.73%
    PRS 75.39
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 23.19
    rCSI 28.86%
    PRS 72.03
  • L6b glutamatergic cortical neuron CL4023038
    CSI 15.29
    rCSI 47.8%
    PRS 75.67
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 14.53
    rCSI 54.9%
    PRS 74.55
  • respiratory basal cell CL0002633
    CSI 11.14
    rCSI 11.53%
    PRS 90.42
  • ependymal cell CL0000065
    CSI 10.3
    rCSI 20.91%
    PRS 70.05
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 10.19
    rCSI 36.66%
    PRS 72.21
  • retina horizontal cell CL0000745
    CSI 8.47
    rCSI 12.92%
    PRS 85.43
  • fibroblast of lung CL0002553
    CSI 7.33
    rCSI 6.82%
    PRS 89.57
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 6.95
    rCSI 40.94%
    PRS 74.7
  • Kupffer cell CL0000091
    CSI 6.49
    rCSI 14.83%
    PRS 89.44
  • mesenchymal cell CL0008019
    CSI 6.3
    rCSI 16%
    PRS 83.18
  • rod bipolar cell CL0000751
    CSI 5.86
    rCSI 10.53%
    PRS 83.1
  • podocyte CL0000653
    CSI 5.73
    rCSI 25.49%
    PRS 89.08
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 5.65
    rCSI 13.51%
    PRS 77.35
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 5.61
    rCSI 13.65%
    PRS 71.95
  • hepatic stellate cell CL0000632
    CSI 5.58
    rCSI 20.91%
    PRS 83.24
  • cardiac endothelial cell CL0010008
    CSI 5.52
    rCSI 22.26%
    PRS 89.1
  • type B pancreatic cell CL0000169
    CSI 4.88
    rCSI 10.81%
    PRS 88.41
  • chondrocyte CL0000138
    CSI 4.88
    rCSI 7.75%
    PRS 83.4
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 3.94
    rCSI 10.26%
    PRS 89.82
  • endocardial cell CL0002350
    CSI 3.8
    rCSI 18.2%
    PRS 84.58
  • blood vessel endothelial cell CL0000071
    CSI 3.57
    rCSI 7.41%
    PRS 86.54
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 3.5
    rCSI 4.04%
    PRS 81.27
  • cardiac neuron CL0010022
    CSI 3.49
    rCSI 11.18%
    PRS 86.69
  • alveolar adventitial fibroblast CL4028006
    CSI 3.46
    rCSI 5.47%
    PRS 89.38
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 3.44
    rCSI 4.42%
    PRS 85.06
  • neural cell CL0002319
    CSI 3.3
    rCSI 12.45%
    PRS 73.01
  • inhibitory interneuron CL0000498
    CSI 3.28
    rCSI 7.57%
    PRS 78.78
  • retinal bipolar neuron CL0000748
    CSI 3.21
    rCSI 6.02%
    PRS 79.26
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 3.21
    rCSI 9.9%
    PRS 90.86
  • adventitial cell CL0002503
    CSI 3.07
    rCSI 7.34%
    PRS 90.9
  • Schwann cell CL0002573
    CSI 2.94
    rCSI 8.37%
    PRS 84.58
  • enteric smooth muscle cell CL0002504
    CSI 2.79
    rCSI 3.98%
    PRS 88.79
  • mesodermal cell CL0000222
    CSI 2.77
    rCSI 3.33%
    PRS 87.28
  • skeletal muscle satellite cell CL0000594
    CSI 2.73
    rCSI 7.99%
    PRS 94.85
  • CD14-positive monocyte CL0001054
    CSI 2.62
    rCSI 3.26%
    PRS 94.48
  • bronchus fibroblast of lung CL2000093
    CSI 2.59
    rCSI 2.11%
    PRS 87.82
  • fibroblast of cardiac tissue CL0002548
    CSI 2.48
    rCSI 11.9%
    PRS 89.09
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.47
    rCSI 2.95%
    PRS 74.38
  • alveolar type 1 fibroblast cell CL4028004
    CSI 2.42
    rCSI 2.65%
    PRS 89.95
  • cerebral cortex endothelial cell CL1001602
    CSI 2.34
    rCSI 4.05%
    PRS 82.49
  • glutamatergic neuron CL0000679
    CSI 2.33
    rCSI 4.78%
    PRS 76.52
  • respiratory suprabasal cell CL4033048
    CSI 2.32
    rCSI 2.98%
    PRS 90.47
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 2.29
    rCSI 3.84%
    PRS 74.24
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 2.26
    rCSI 4.11%
    PRS 81.69
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.98
    rCSI 3.18%
    PRS 75.43
  • peripheral nervous system neuron CL2000032
    CSI 1.95
    rCSI 2.66%
    PRS 81.79
  • basal cell CL0000646
    CSI 1.92
    rCSI 2.56%
    PRS 85.86
  • adipocyte CL0000136
    CSI 1.83
    rCSI 2.35%
    PRS 79.74
  • conjunctival epithelial cell CL1000432
    CSI 1.8
    rCSI 2.75%
    PRS 87.87
  • retinal ganglion cell CL0000740
    CSI 1.72
    rCSI 3.8%
    PRS 77.01
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.69
    rCSI 5.28%
    PRS 77.6
  • GABAergic neuron CL0000617
    CSI 1.66
    rCSI 5.56%
    PRS 74.4
  • Hofbauer cell CL3000001
    CSI 1.66
    rCSI 3.13%
    PRS 93.67
  • stromal cell CL0000499
    CSI 1.41
    rCSI 3.97%
    PRS 84.26
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.41
    rCSI 2.49%
    PRS 73.75
  • renal interstitial pericyte CL1001318
    CSI 1.32
    rCSI 3.65%
    PRS 85.29
  • lung pericyte CL0009089
    CSI 1.3
    rCSI 3.42%
    PRS 92.69
  • parietal epithelial cell CL1000452
    CSI 1.19
    rCSI 3.19%
    PRS 82.4
  • stromal cell of ovary CL0002132
    CSI 1.17
    rCSI 3.21%
    PRS 92.08
  • dopaminergic neuron CL0000700
    CSI 1.07
    rCSI 6.07%
    PRS 77.23
  • invaginating midget bipolar cell CL4033034
    CSI 0.86
    rCSI 5.05%
    PRS 79.87
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 0.85
    rCSI 2.8%
    PRS 76.26
  • serotonergic neuron CL0000850
    CSI 0.82
    rCSI 3.65%
    PRS 73.92
  • GABAergic amacrine cell CL4030027
    CSI 0.8
    rCSI 2.75%
    PRS 75.57
  • diffuse bipolar 3a cell CL4033029
    CSI 0.77
    rCSI 5.27%
    PRS 80.51
  • blood vessel smooth muscle cell CL0019018
    CSI 0.77
    rCSI 6.25%
    PRS 84.87
  • fibroblast of breast CL4006000
    CSI 0.76
    rCSI 3.21%
    PRS 90.99
  • direct pathway medium spiny neuron CL4023026
    CSI 0.68
    rCSI 16.17%
    PRS 71.91
  • diffuse bipolar 1 cell CL4033027
    CSI 0.67
    rCSI 5.04%
    PRS 78.14
  • diffuse bipolar 4 cell CL4033031
    CSI 0.65
    rCSI 7.39%
    PRS 76.49
  • endothelial cell of placenta CL0009092
    CSI 0.6
    rCSI 2.97%
    PRS 92.9
  • flat midget bipolar cell CL4033033
    CSI 0.57
    rCSI 4.09%
    PRS 78.78
  • H2 horizontal cell CL0004218
    CSI 0.56
    rCSI 2.8%
    PRS 82.88
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.33
    rCSI 7.89%
    PRS 72.33
  • central nervous system neuron CL2000029
    CSI 0.32
    rCSI 2.35%
    PRS 79.02

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.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [TSHZ3](/details-gene/57616) (teashirt zinc finger homeobox 3) is a protein-coding gene located on chromosome 19q12 that encodes a DNA-binding transcription factor. This protein plays a crucial role in transcriptional regulation, particularly within the central nervous system. Expression data reveals that [TSHZ3](/details-gene/57616) is a highly significant marker for specific neuronal subtypes in the cerebral cortex, including both [sst GABAergic cortical interneurons](/details-cell/CL4023017) and various glutamatergic projection neurons. Consistent with this expression profile, functional annotations link the gene to synaptic plasticity and neurotransmission. Clinical research has established that deletions or mutations in [TSHZ3](/details-gene/57616) are associated with an autism spectrum disorder syndrome, highlighting its critical role in proper neurodevelopment [Link](https://doi.org/10.1038/ng.3681). ## Cellular Roles and Expression Landscape The expression profile of [TSHZ3](/details-gene/57616) underscores its importance as a key transcriptional regulator in the nervous system, with a particularly specialized role in the cerebral cortex. **Overall**, the gene shows the highest significance in distinct neuronal populations. It is the top marker for [sst GABAergic cortical interneurons](/details-cell/CL4023017) (CSI: 32.37) and also exhibits high significance in [pvalb GABAergic cortical interneurons](/details-cell/CL4023018) (CSI: 23.19). This suggests a fundamental role in establishing or maintaining the identity and function of major inhibitory interneuron classes. Concurrently, [TSHZ3](/details-gene/57616) is a prominent marker for several excitatory glutamatergic neuron subtypes, including [L6b glutamatergic cortical neurons](/details-cell/CL4023038) (CSI: 15.29) and multiple classes of projecting neurons such as [L5 extratelencephalic projecting glutamatergic cortical neurons](/details-cell/CL4023041). This dual prominence in both inhibitory and excitatory neurons points to a central role in orchestrating the complex circuitry and synaptic balance of the cortex. Beyond the cortex, [TSHZ3](/details-gene/57616) is significantly expressed in other specialized cell types, indicating broader functions. These include [respiratory basal cells](/details-cell/CL0002633), [ependymal cells](/details-cell/CL0000065), [retina horizontal cells](/details-cell/CL0000745), and [fibroblasts of the lung](/details-cell/CL0002553). This diverse expression pattern is consistent with literature reports of its role in developmental processes outside the brain, such as ureteral smooth muscle differentiation [Link](https://doi.org/10.1242/dev.022442). ## Pathways and Molecular Function [TSHZ3](/details-gene/57616) functions primarily as a DNA-binding transcription factor, consistent with its molecular function annotations for [Dna-binding transcription factor activity, rna polymerase ii-specific](/details-gene/https://www.ebi.ac.uk/QuickGO/term/GO:0000981) and [Chromatin binding](/details-gene/https://www.ebi.ac.uk/QuickGO/term/GO:0003682). It localizes to the [Nucleus](/details-gene/https://www.ebi.ac.uk/QuickGO/term/GO:0005634) and specifically the [Nucleoplasm](/details-gene/https://www.ebi.ac.uk/QuickGO/term/GO:0005654) and [Chromatin](/details-gene/https://www.ebi.ac.uk/QuickGO/term/GO:0000785), where it exerts its function by modulating gene expression. The biological processes associated with [TSHZ3](/details-gene/57616) are tightly aligned with its high expression in cortical neurons. Its involvement in [Long-term synaptic potentiation](/details-gene/https://www.ebi.ac.uk/QuickGO/term/GO:0060291) and [Positive regulation of synaptic transmission, glutamatergic](/details-gene/https://www.ebi.ac.uk/QuickGO/term/GO:0051968) provides a direct functional link to synaptic plasticity and learning. The annotation for [Negative regulation of dna-templated transcription](/details-gene/https://www.ebi.ac.uk/QuickGO/term/GO:0045892) suggests it can act as a transcriptional repressor, a common mechanism for homeobox proteins in guiding cellular differentiation and function. Its reported interaction with FE65 to inhibit caspase-4 expression provides a specific example of its repressive activity [Link](https://doi.org/10.1371/journal.pone.0005071). ## Research Directions The strong association of [TSHZ3](/details-gene/57616) with neurodevelopmental disorders, combined with its specific expression pattern, opens several avenues for future investigation. Its high significance in both inhibitory and excitatory cortical neurons suggests it is a nexus for regulating cortical circuit formation and function. Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis:** [TSHZ3](/details-gene/57616) acts as a master transcriptional regulator that establishes and maintains the excitatory/inhibitory balance in the cerebral cortex. Its haploinsufficiency, as seen in some autism syndromes, disrupts the gene networks governing synaptic function in both GABAergic and glutamatergic neurons, leading to circuit-level dysfunction. 2. **Hypothesis:** The role of [TSHZ3](/details-gene/57616) in diverse cell types like [respiratory basal cells](/details-cell/CL0002633) and [fibroblasts](/details-cell/CL0002553) points to a conserved function in stem/progenitor cell maintenance and differentiation. In these contexts, [TSHZ3](/details-gene/57616) may regulate cellular plasticity and response to injury. A key experiment to test the first hypothesis would involve the use of advanced mouse models. One could generate cell-type-specific conditional knockouts of *Tshz3* in either GABAergic (e.g., via Gad2-Cre or Sst-Cre driver lines) or glutamatergic (e.g., via Emx1-Cre) neurons. Subsequent analysis using single-cell RNA-sequencing would reveal the downstream transcriptional consequences in each population, while slice electrophysiology could directly measure changes in synaptic transmission and intrinsic excitability. These molecular and cellular changes could then be correlated with behavioral phenotypes relevant to autism spectrum disorder. Given that [TSHZ3](/details-gene/57616) is an intracellular transcription factor, it represents a challenging therapeutic target for conventional small molecules. Furthermore, since its loss-of-function is pathogenic, therapeutic strategies would need to focus on restoring or augmenting its activity rather than inhibition. This could potentially involve gene therapy approaches or the identification of downstream pathways regulated by [TSHZ3](/details-gene/57616) that contain more druggable targets. Understanding the precise molecular mechanisms it governs in specific neuronal subtypes is a critical first step toward developing such strategies.

Genular Protein ID: 617704511

Symbol: TSH3_HUMAN

Name: Teashirt homolog 3

UniProtKB Accession Codes:

Q63HK5 A1L0U7 Q9H0G6 Q9P254

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 14 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 SIGNOR 1 SMART 2 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 10819331

Title: Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.

PubMed ID: 10819331

DOI: 10.1093/dnares/7.2.143

PubMed ID: 11230166

Title: Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.

PubMed ID: 11230166

DOI: 10.1101/gr.gr1547r

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 18776146

Title: Teashirt 3 is necessary for ureteral smooth muscle differentiation downstream of SHH and BMP4.

PubMed ID: 18776146

DOI: 10.1242/dev.022442

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 19343227

Title: FE65 binds Teashirt, inhibiting expression of the primate-specific caspase-4.

PubMed ID: 19343227

DOI: 10.1371/journal.pone.0005071

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 27668656

Title: TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons.

PubMed ID: 27668656

DOI: 10.1038/ng.3681

PubMed ID: 19745106

Title: Analysis of TSHZ2 and TSHZ3 genes in congenital pelvi-ureteric junction obstruction.

PubMed ID: 19745106

DOI: 10.1093/ndt/gfp453

Sequence Information:

  • Length: 1081
  • Mass: 118566
  • Checksum: B4E0A4347B04E74A
  • Sequence:
    • MPRRKQQAPR RAAAYVSEEL KAAALVDEGL DPEEHTADGE PSAKYMCPEK ELARACPSYQ 
NSPAAEFSCH EMDSESHISE TSDRMADFES GSIKNEEETK EVTVPLEDTT VSDSLEQMKA 
VYNNFLSNSY WSNLNLNLHQ PSSEKNNGSS SSSSSSSSSC GSGSFDWHQS AMAKTLQQVS 
QSRMLPEPSL FSTVQLYRQS SKLYGSIFTG ASKFRCKDCS AAYDTLVELT VHMNETGHYR 
DDNHETDNNN PKRWSKPRKR SLLEMEGKED AQKVLKCMYC GHSFESLQDL SVHMIKTKHY 
QKVPLKEPVT PVAAKIIPAT RKKASLELEL PSSPDSTGGT PKATISDTND ALQKNSNPYI 
TPNNRYGHQN GASYAWHFEA RKSQILKCME CGSSHDTLQE LTAHMMVTGH FIKVTNSAMK 
KGKPIVETPV TPTITTLLDE KVQSVPLAAT TFTSPSNTPA SISPKLNVEV KKEVDKEKAV 
TDEKPKQKDK PGEEEEKCDI SSKYHYLTEN DLEESPKGGL DILKSLENTV TSAINKAQNG 
TPSWGGYPSI HAAYQLPNMM KLSLGSSGKS TPLKPMFGNS EIVSPTKNQT LVSPPSSQTS 
PMPKTNFHAM EELVKKVTEK VAKVEEKMKE PDGKLSPPKR ATPSPCSSEV GEPIKMEASS 
DGGFRSQENS PSPPRDGCKD GSPLAEPVEN GKELVKPLAS SLSGSTAIIT DHPPEQPFVN 
PLSALQSVMN IHLGKAAKPS LPALDPMSML FKMSNSLAEK AAVATPPPLQ SKKADHLDRY 
FYHVNNDQPI DLTKGKSDKG CSLGSVLLSP TSTAPATSSS TVTTAKTSAV VSFMSNSPLR 
ENALSDISDM LKNLTESHTS KSSTPSSISE KSDIDGATLE EAEESTPAQK RKGRQSNWNP 
QHLLILQAQF AASLRQTSEG KYIMSDLSPQ ERMHISRFTG LSMTTISHWL ANVKYQLRRT 
GGTKFLKNLD TGHPVFFCND CASQIRTPST YISHLESHLG FRLRDLSKLS TEQINSQIAQ 
TKSPSEKMVT SSPEEDLGTS YQCKLCNRTF ASKHAVKLHL SKTHGKSPED HLLYVSELEK 
Q