Details for: DLX6

Gene ID: 1750

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: DLX6

Ensembl ID: ENSG00000006377

Description: distal-less homeobox 6

Cell Significance Landscape

Associated with

Significant Cells

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

  • epithelial cell CL0000066
    CSI 10.43
    rCSI 16.03%
    PRS 84.51
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 5.29
    rCSI 9.34%
    PRS 85.41
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 4.11
    rCSI 4.74%
    PRS 88.74
  • extravillous trophoblast CL0008036
    CSI 3.72
    rCSI 4.6%
    PRS 93.19
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.36
    rCSI 4.18%
    PRS 83.89
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 3
    rCSI 8.87%
    PRS 94.25
  • placental villous trophoblast CL2000060
    CSI 2.26
    rCSI 3.49%
    PRS 93.14
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.03
    rCSI 2.62%
    PRS 86.92
  • peripheral nervous system neuron CL2000032
    CSI 1.48
    rCSI 2.01%
    PRS 89.95
  • odontoblast CL0000060
    CSI 0.29
    rCSI 6.56%
    PRS 97.3

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)

Loading network (please wait)...

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 [DLX6](/details-gene/1750) (distal-less homeobox 6) is a protein-coding gene located on chromosome 7q21.3. It encodes a homeobox-containing transcription factor that belongs to the Dlx gene family, which are critical regulators of embryonic development. Functionally, [DLX6](/details-gene/1750) is primarily involved in [regulation of transcription by rna polymerase ii](/details-gene/GO:0006357) and plays a pivotal role in morphogenesis and cell differentiation, particularly in the development of the nervous system, skeleton, and craniofacial structures ([Link](https://pubmed.ncbi.nlm.nih.gov/7907794/)). Expression data highlights its significant role in establishing the identity of specific cell lineages, with pronounced marker status in [epithelial cells](/details-cell/CL0000066) and various subtypes of [GABAergic cortical interneurons](/details-cell/CL0010011). ## Cellular Roles and Expression Landscape The **Overall** expression profile of [DLX6](/details-gene/1750) reveals a highly specific pattern of cellular significance, pointing to its function as a key lineage-defining transcription factor. Its most prominent role is observed in [epithelial cells](/details-cell/CL0000066), where it displays the highest Cell Significance Index (CSI: 10.43), suggesting it is a defining marker for this cell type. Beyond epithelial tissues, [DLX6](/details-gene/1750) is a crucial determinant in the nervous system, particularly for inhibitory interneuron populations. It shows high significance in [caudal ganglionic eminence derived cortical interneurons](/details-cell/CL4023064) (CSI: 5.29), [pvalb GABAergic cortical interneurons](/details-cell/CL4023018) (CSI: 3.36), and [cerebral cortex GABAergic interneurons](/details-cell/CL0010011) (CSI: 3.00). This is consistent with its established role in specifying the fate of these neurons during cortical development. Additionally, [DLX6](/details-gene/1750) is significantly expressed in developmental tissues such as the placenta, specifically in [extravillous trophoblasts](/details-cell/CL0008036) and [placental villous trophoblasts](/details-cell/CL2000060). Its activity in [odontoblasts](/details-cell/CL0000060) aligns with its documented involvement in skeletal and craniofacial development. ## Pathways and Molecular Function As a homeobox protein, [DLX6](/details-gene/1750) functions as a sequence-specific transcription factor. Its molecular activities are centered on [DNA-binding transcription factor activity, rna polymerase ii-specific](/details-gene/GO:0000981), and it localizes to the [nucleus](/details-gene/GO:0005634) and [chromatin](/details-gene/GO:0000785) to exert its regulatory effects. The biological processes governed by [DLX6](/details-gene/1750) are predominantly developmental. It is integral to [anatomical structure formation involved in morphogenesis](/details-gene/GO:0048646), [nervous system development](/details-gene/GO:0007399), and [skeletal system development](/details-gene/GO:0001501). Reactome pathway analysis further clarifies its role in fundamental transcriptional mechanisms, including [Gene expression (transcription)](/details-pathway/R-HSA-74160) and [RNA polymerase II transcription](/details-pathway/R-HSA-73857). Notably, its involvement in the [Regulation of RUNX2 expression and activity](/details-pathway/R-HSA-8939902) pathway provides a direct molecular link to its function in osteogenesis and skeletal formation. ## Research Directions The specific expression pattern and established functions of [DLX6](/details-gene/1750) suggest several avenues for future research, particularly concerning neurodevelopment and epithelial biology. **Proposed Hypotheses:** 1. Given its high significance in multiple subtypes of GABAergic interneurons, [DLX6](/details-gene/1750) may act as a terminal selector gene responsible for not only specifying interneuron fate but also for maintaining their mature functional identity and subtype-specific connectivity in the adult cortex. 2. Based on its top marker status in [epithelial cells](/details-cell/CL0000066) and its role in [positive regulation of epithelial cell proliferation](/details-gene/GO:0050679), aberrant expression or dysregulation of [DLX6](/details-gene/1750) could be a contributing factor to the initiation or progression of epithelial-derived cancers (carcinomas) by disrupting the balance between cell proliferation and differentiation. **Key Experimental Approach:** To test the hypothesis that [DLX6](/details-gene/1750) is critical for maintaining interneuron identity (Hypothesis 1), a conditional knockout mouse model could be employed. Using a tamoxifen-inducible Cre-driver line specific to mature cortical interneurons (e.g., Pvalb-CreER or Sst-CreER), the *Dlx6* gene could be deleted in adult mice. The impact of its loss could then be assessed through a combination of single-cell RNA sequencing (scRNA-seq) to detect shifts in the transcriptomic identity of the targeted neurons, and electrophysiological recordings (patch-clamp) to measure functional changes in their firing properties and synaptic integration. **Therapeutic Potential:** As an intracellular transcription factor, [DLX6](/details-gene/1750) represents a challenging therapeutic target for traditional small molecule inhibitors. However, its highly specific expression pattern makes it and its downstream pathways potentially attractive for targeted therapies. If loss-of-function mutations in [DLX6](/details-gene/1750) are linked to neurodevelopmental disorders like epilepsy or autism spectrum disorder, gene therapy approaches aimed at restoring its expression in specific neuronal progenitors could be a viable long-term strategy. Conversely, if its aberrant re-expression is demonstrated in certain cancers, strategies to inhibit its activity or its key downstream effectors, perhaps using targeted nucleic acid-based therapies like siRNAs, might be explored.

Genular Protein ID: 2067203485

Symbol: DLX6_HUMAN

Name: Homeobox protein DLX-6

UniProtKB Accession Codes:

P56179 A4D1I2 B3KSQ0 J3KR92 Q3ZAR6 Q9UPL2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 9 Ensembl 1 ExpressionAtlas 1 GO 17 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 1 RefSeq 1 SMART 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: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

PubMed ID: 12690205

Title: Human chromosome 7: DNA sequence and biology.

PubMed ID: 12690205

DOI: 10.1126/science.1083423

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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 7907794

Title: Cloning and characterization of two members of the vertebrate Dlx gene family.

PubMed ID: 7907794

DOI: 10.1073/pnas.91.6.2250

Sequence Information:

  • Length: 175
  • Mass: 19708
  • Checksum: F5552738D7E0CB84
  • Sequence:
    • MSHSQHSPYL QSYHNSSAAA QTRGDDTDQQ KTTVIENGEI RFNGKGKKIR KPRTIYSSLQ 
LQALNHRFQQ TQYLALPERA ELAASLGLTQ TQVKIWFQNK RSKFKKLLKQ GSNPHESDPL 
QGSAALSPRS PALPPVWDVS ASAKGVSMPP NSYMPGYSHW YSSPHQDTMQ RPQMM