Details for: DACH2

Gene ID: 117154

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: DACH2

Ensembl ID: ENSG00000126733

Description: dachshund family transcription factor 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Development of primary female sexual characteristics
    (GO:0046545)
  • Dna-binding transcription factor activity, rna polymerase ii-specific
    (GO:0000981)
  • Nucleus
    (GO:0005634)
  • Regulation of transcription by rna polymerase ii
    (GO:0006357)
  • Rna polymerase ii cis-regulatory region sequence-specific dna binding
    (GO:0000978)
  • Transcription regulator complex
    (GO:0005667)

Significant Cells

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

  • GABAergic amacrine cell CL4030027
    CSI 10.27
    rCSI 35.17%
    PRS 77.26
  • neuroendocrine cell CL0000165
    CSI 9.36
    rCSI 36.18%
    PRS 93
  • sncg GABAergic cortical interneuron CL4023015
    CSI 7.76
    rCSI 12.47%
    PRS 77.55
  • glioblast CL0000030
    CSI 7.42
    rCSI 11.83%
    PRS 82.42
  • amacrine cell CL0000561
    CSI 7.03
    rCSI 20.37%
    PRS 81.26
  • renal interstitial pericyte CL1001318
    CSI 5.69
    rCSI 15.69%
    PRS 86.99
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 5.49
    rCSI 13.33%
    PRS 74.32
  • ependymal cell CL0000065
    CSI 5.39
    rCSI 10.93%
    PRS 71.95
  • sst GABAergic cortical interneuron CL4023017
    CSI 5.1
    rCSI 6.58%
    PRS 77.68
  • L6b glutamatergic cortical neuron CL4023038
    CSI 5.06
    rCSI 15.81%
    PRS 77.95
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 4.81
    rCSI 5.55%
    PRS 82.72
  • inhibitory interneuron CL0000498
    CSI 4.74
    rCSI 10.93%
    PRS 80.58
  • VIP GABAergic cortical interneuron CL4023016
    CSI 4.42
    rCSI 5.28%
    PRS 76.59
  • Mueller cell CL0000636
    CSI 4.14
    rCSI 9.44%
    PRS 83.25
  • retinal bipolar neuron CL0000748
    CSI 4.13
    rCSI 7.74%
    PRS 81.17
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 3.87
    rCSI 4.97%
    PRS 86.39
  • lung neuroendocrine cell CL1000223
    CSI 3.82
    rCSI 5.65%
    PRS 91.61
  • podocyte CL0000653
    CSI 3.55
    rCSI 15.79%
    PRS 90.41
  • kidney interstitial fibroblast CL1000692
    CSI 3.34
    rCSI 17.74%
    PRS 82.76
  • endocardial cell CL0002350
    CSI 3.11
    rCSI 14.89%
    PRS 86.14
  • GABAergic neuron CL0000617
    CSI 3.09
    rCSI 10.37%
    PRS 76.3
  • neural cell CL0002319
    CSI 2.68
    rCSI 10.12%
    PRS 74.59
  • glycinergic amacrine cell CL4030028
    CSI 2.65
    rCSI 6.9%
    PRS 84.07
  • mesodermal cell CL0000222
    CSI 2.54
    rCSI 3.04%
    PRS 88.67
  • retinal ganglion cell CL0000740
    CSI 2.27
    rCSI 5.02%
    PRS 79.08
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.19
    rCSI 3.87%
    PRS 75.99
  • neural progenitor cell CL0011020
    CSI 2.02
    rCSI 8.9%
    PRS 79.4
  • type B pancreatic cell CL0000169
    CSI 1.77
    rCSI 3.92%
    PRS 89.74
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.72
    rCSI 6.21%
    PRS 74.46
  • diffuse bipolar 3b cell CL4033030
    CSI 1.68
    rCSI 11.12%
    PRS 84.14
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.55
    rCSI 5.84%
    PRS 76.78
  • flat midget bipolar cell CL4033033
    CSI 1.49
    rCSI 10.67%
    PRS 80.62
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.48
    rCSI 2.49%
    PRS 76.53
  • melanocyte of skin CL1000458
    CSI 1.34
    rCSI 1.83%
    PRS 60.5
  • GABAergic interneuron CL0011005
    CSI 1.28
    rCSI 20.25%
    PRS 90.32
  • starburst amacrine cell CL0004232
    CSI 0.98
    rCSI 8.28%
    PRS 77.09
  • H2 horizontal cell CL0004218
    CSI 0.92
    rCSI 4.56%
    PRS 84.34
  • stromal cell CL0000499
    CSI 0.91
    rCSI 2.56%
    PRS 85.9
  • direct pathway medium spiny neuron CL4023026
    CSI 0.84
    rCSI 20.13%
    PRS 74.16
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.76
    rCSI 18.27%
    PRS 74.35
  • medium spiny neuron CL1001474
    CSI 0.47
    rCSI 4.05%
    PRS 81.51
  • blood vessel smooth muscle cell CL0019018
    CSI 0.43
    rCSI 3.49%
    PRS 86.75

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.

Comma-separated if multiple.
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 [DACH2](/details-gene/117154) (dachshund family transcription factor 2) is a protein-coding gene located on the X chromosome at position Xq21.2 ([Link](https://doi.org/10.1038/nature03440)). As a member of the dachshund family, it functions as a DNA-binding transcription factor that regulates gene expression by binding to RNA polymerase II cis-regulatory regions. Functionally, [DACH2](/details-gene/117154) is annotated with roles in the '[regulation of transcription by rna polymerase ii](/details-go/GO:0006357)' and the '[development of primary female sexual characteristics](/details-go/GO:0046545)'. Its expression is highly enriched in specific neuronal populations, particularly inhibitory interneurons of the retina and cortex, such as '[GABAergic amacrine cell](/details-cell/CL4030027)' and '[sncg GABAergic cortical interneuron](/details-cell/CL4023015)', suggesting a crucial role in the development and function of the central nervous system. Clinical associations for this gene are cataloged under OMIM entry [300608](https://omim.org/entry/300608). ## Cellular Roles and Expression Landscape The expression profile of [DACH2](/details-gene/117154) demonstrates a highly specialized role within the central nervous system. **Overall**, the gene shows its highest significance in distinct neuronal and neural-associated cell types. It is an exceptional marker for inhibitory neurons, particularly within the retina and cortex. The highest significance score is observed in '[GABAergic amacrine cell](/details-cell/CL4030027)' (CSI: 10.27), a type of inhibitory interneuron in the retina. This neuronal specificity is further supported by high significance in multiple cortical GABAergic interneuron subtypes, including '[sncg GABAergic cortical interneuron](/details-cell/CL4023015)' (CSI: 7.76), '[sst GABAergic cortical interneuron](/details-cell/CL4023017)' (CSI: 5.10), and '[VIP GABAergic cortical interneuron](/details-cell/CL4023016)' (CSI: 4.42). In addition to inhibitory neurons, [DACH2](/details-gene/117154) is also significant in glutamatergic neurons, such as '[L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040)' (CSI: 5.49) and '[L6b glutamatergic cortical neuron](/details-cell/CL4023038)' (CSI: 5.06). Beyond mature neurons, [DACH2](/details-gene/117154) is also a marker for '[neuroendocrine cell](/details-cell/CL0000165)' (CSI: 9.36), '[neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338)' (CSI: 4.81), and glial-like cells such as '[ependymal cell](/details-cell/CL0000065)' (CSI: 5.39) and '[Mueller cell](/details-cell/CL0000636)' (CSI: 4.14). Notably, its high expression in '[glioblast](/details-cell/CL0000030)' (CSI: 7.42) suggests its potential involvement in the pathology of this brain tumor. ## Pathways and Molecular Function Consistent with its identification as a transcription factor, the molecular functions of [DACH2](/details-gene/117154) are centered on gene regulation. Gene Ontology annotations confirm its localization to the '[nucleus](/details-go/GO:0005634)' and its participation in the '[transcription regulator complex](/details-go/GO:0005667)'. Its primary molecular activities include '[Dna-binding transcription factor activity, rna polymerase ii-specific](/details-go/GO:0000981)' and '[Rna polymerase ii cis-regulatory region sequence-specific dna binding](/details-go/GO:0000978)'. The biological processes it regulates are directly linked to its expression pattern. Its role in the '[regulation of transcription by rna polymerase ii](/details-go/GO:0006357)' is the fundamental mechanism by which it likely directs the differentiation and maintenance of the specific neuronal subtypes in which it is highly expressed. The annotation for '[Development of primary female sexual characteristics](/details-go/GO:0046545)' is noteworthy given the gene's location on the X chromosome and suggests a potential role in mediating sex-specific differences in neural development or function. ## Research Directions The specific expression pattern of [DACH2](/details-gene/117154) in distinct neuronal subtypes and its function as a transcription factor suggest it is a critical determinant of cell identity in the central nervous system. **Proposed Hypotheses:** 1. Given its high significance in multiple classes of GABAergic neurons, [DACH2](/details-gene/117154) may function as a master regulator required for the terminal differentiation or functional maintenance of specific inhibitory interneuron populations in the retina and cerebral cortex. 2. The high expression in '[glioblast](/details-cell/CL0000030)', a malignant brain tumor, suggests that aberrant re-activation or dysregulation of [DACH2](/details-gene/117154) may contribute to gliomagenesis by promoting a de-differentiated, progenitor-like state that supports tumor growth. 3. Based on its X-chromosomal location and its role in '[Development of primary female sexual characteristics](/details-go/GO:0046545)', [DACH2](/details-gene/117154) may regulate sexually dimorphic aspects of neural circuit development, potentially influencing brain structures or functions that differ between males and females. **Key Experimental Approach:** To test the hypothesis that [DACH2](/details-gene/117154) is a key regulator of inhibitory neuron identity (Hypothesis 1), one could generate a conditional knockout of [DACH2](/details-gene/117154) in a mouse model using a pan-GABAergic driver line (e.g., *Gad2-Cre*). Single-cell RNA sequencing (scRNA-seq) and electrophysiological analysis of cortical and retinal tissues from these mice compared to wild-type littermates would reveal whether the absence of [DACH2](/details-gene/117154) leads to a loss of specific interneuron subtypes, a shift in their molecular identity, or functional deficits in inhibitory neurotransmission. **Therapeutic Potential:** The strong and specific expression of [DACH2](/details-gene/117154) in '[glioblast](/details-cell/CL0000030)' makes it a potential therapeutic target for this aggressive cancer. As a nuclear transcription factor, it is not easily targetable by conventional antibodies. However, its activity could potentially be modulated through small molecule inhibitors designed to disrupt its DNA binding or its interaction with other co-factors in the transcriptional complex. Given its presumed pro-proliferative or anti-differentiation role in the cancer context, an **inhibition** strategy would be the therapeutic goal. The development of such targeted therapies would require a deeper understanding of its precise molecular mechanism in glioblastoma cells.

Genular Protein ID: 1991350429

Symbol: DACH2_HUMAN

Name: Dachshund homolog 2

UniProtKB Accession Codes:

Q96NX9 B1AJV3 B4DQG3 Q8NAY3 Q8ND17 Q96N55

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 14 Ensembl 4 ExpressionAtlas 1 GO 6 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 RNAct 1 RefSeq 4 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

PubMed ID: 17974005

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

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

Sequence Information:

  • Length: 599
  • Mass: 65323
  • Checksum: 4EE435720A83BAA0
  • Sequence:
    • MAVSASPVIS ATSSGAGVPG GLFRAEPLYS TPREPPRLTP NMINSFVVNN HSNSAGGGGR 
GNTNTNECRM VDMHGMKVAS FLMDGQELIC LPQVFDLFLK HLVGGLHTVY TKLKRLDISP 
VVCTVEQVRI LRGLGAIQPG VNRCKLITRK DFETLFTDCT NARRKRQMTR KQAVNSSRPG 
RPPKRSLGVL QENARLLTHA VPGLLSPGLI TPTGITAAAM AEAMKLQKMK LMAMNTLQGN 
GSQNGTESEP DDLNSNTGGS ESSWDKDKMQ SPFAAPGPQH GIAHAALAGQ PGIGGAPTLN 
PLQQNHLLTN RLDLPFMMMP HPLLPVSLPP ASVAMAMNQM NHLNTIANMA AAAQIHSPLS 
RAGTSVIKER IPESPSPAPS LEENHRPGSQ TSSHTSSSVS SSPSQMDHHL ERMEEVPVQI 
PIMKSPLDKI QLTPGQALPA GFPGPFIFAD SLSSVETLLT NIQGLLKVAL DNARIQEKQI 
QQEKKELRLE LYREREIREN LERQLAVELQ SRTTMQKRLK KEKKTKRKLQ EALEFESKRR 
EQVEQALKQA TTSDSGLRML KDTGIPDIEI ENNGTPHDSA AMQGGNYYCL EMAQQLYSA

Genular Protein ID: 2362393333

Symbol: A8K3I1_HUMAN

Name: N/A

UniProtKB Accession Codes:

A8K3I1

Database IDs:

ARBA 2 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 1 Gene3D 1 InterPro 4 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 3 SAM 2 SUPFAM 1

Sequence Information:

  • Length: 599
  • Mass: 65366
  • Checksum: 6D3622BC6C8566C4
  • Sequence:
    • MAVSASPVIS ATSSGAGVPG GLFRAEPLYS TPREPPRLTP NMINSFVVNN HSNSAGGGGR 
GNTNTNECRM VDMHGMKVAS FLMDGQELIC LPQVFDLFLK HLVGGLHTVY TELKRLDISP 
VVCTVEQVRI LRGLGAIQPG VNRCKLITRK DFETLFTDCT NARRKRQMTR KQAVNSSRPG 
RPPKRSLGVL QENARLLTHA VPGLLSPGLI TPTGITAAAM AEAMKLQKMK LMAMNTLQGN 
GSQNGTESEP DDLNSNTGGS ESSWDKDKMQ SPFAAPGPQH GIAHAALAVQ PGIGGAPTLN 
PLQQNHLLTN RLDLPFMMMP HPLLPVSLPP ASVAMAMNQM NHLNTIANMA AAAQIHSPLS 
RAGTSVIKER IPESPSPAPS LEENHRPGSQ TSSHTSSSVS SSPSQMDHHL ERMEEVPVQI 
PIMKSPLDKI QLTPGQALPA GFPGPFIFAD SLSSVETLLT NIQGLLKVAL DNARIQEKQI 
QQEKKELRLE LYREREIREN LERQLAVELQ SRTTMQKRLK KEKKTKRKLQ EALEFESKRR 
EQVEQALKQA TTSDSGLRML KDTGIPDIEI ENNGTPHDSA AMQGGNYYCL EMAQQLYSA