Details for: HOXD1

Gene ID: 3231

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: HOXD1

Ensembl ID: ENSG00000128645

Description: homeobox D1

Cell Significance Landscape

Associated with

Significant Cells

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

  • fallopian tube secretory epithelial cell CL4030006
    CSI 5.38
    rCSI 5.18%
    PRS 98.64
  • epithelial cell of lung CL0000082
    CSI 4.75
    rCSI 3.94%
    PRS 99.46
  • ciliated epithelial cell CL0000067
    CSI 3.1
    rCSI 2.73%
    PRS 96.86
  • intestinal epithelial cell CL0002563
    CSI 2.72
    rCSI 2.85%
    PRS 98.46
  • peripheral nervous system neuron CL2000032
    CSI 2.17
    rCSI 2.96%
    PRS 97.71

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

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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 [HOXD1](/details-gene/3231) is a protein-coding gene located on chromosome 2q31.1 that encodes Homeobox protein Hox-D1, a member of the homeobox family of DNA-binding transcription factors. These proteins are crucial regulators of morphogenesis and development. Functionally, [HOXD1](/details-gene/3231) is involved in fundamental processes such as the `[Activation of hox genes during differentiation](/details-pathway/R-HSA-5619507)` and `[Embryonic skeletal system development](/details-pathway/GO:0048706)`. **Overall**, expression data indicates that [HOXD1](/details-gene/3231) has its highest significance in various specialized epithelial cells, including `[fallopian tube secretory epithelial cell](/details-cell/CL4030006)` and `[epithelial cell of lung](/details-cell/CL0000082)`, suggesting a key role in maintaining the identity and function of these tissues in adults. Its association with OMIM entry `[142987](https://omim.org/entry/142987)` underscores its clinical relevance. ## Cellular Roles and Expression Landscape The expression profile of [HOXD1](/details-gene/3231) points to a specialized role in differentiated cell types, particularly those of epithelial origin. - **Epithelial Tissues:** In the **Overall** context, [HOXD1](/details-gene/3231) shows the highest significance in several epithelial cell types. It is a top marker for `[fallopian tube secretory epithelial cell](/details-cell/CL4030006)` (CSI: 5.38), `[epithelial cell of lung](/details-cell/CL0000082)` (CSI: 4.75), and `[ciliated epithelial cell](/details-cell/CL0000067)` (CSI: 3.10). Its notable expression in `[intestinal epithelial cell](/details-cell/CL0002563)` further supports its role as a key transcriptional regulator in maintaining the integrity and function of mucosal surfaces. - **Nervous System:** Beyond epithelial tissues, [HOXD1](/details-gene/3231) is also significantly expressed in the `[peripheral nervous system neuron](/details-cell/CL2000032)` (CSI: 2.17). This is consistent with its annotated function in `[Neuron differentiation](/details-pathway/GO:0030182)` and suggests a potential role in neuronal development or the maintenance of specific neuronal subtypes. The characterization and full-length sequencing of [HOXD1](/details-gene/3231) have been foundational to understanding its expression, as detailed in several large-scale cDNA projects ([Link](https://doi.org/10.1038/ng1285), [Link](https://doi.org/10.1101/gr.2596504)) and initial characterization studies ([Link](https://doi.org/10.1023/a:1011048931477)). ## Pathways and Molecular Function [HOXD1](/details-gene/3231) functions as a sequence-specific DNA-binding transcription factor. Its molecular activities are primarily directed at regulating gene expression programs essential for development and cellular differentiation. - **Molecular Function:** Gene Ontology annotations confirm its role as a transcription factor with `[Dna-binding transcription factor activity, rna polymerase ii-specific](/details-pathway/GO:0000981)` and `[Rna polymerase ii cis-regulatory region sequence-specific dna binding](/details-pathway/GO:0000978)`. - **Cellular Localization:** Consistent with its function, [HOXD1](/details-gene/3231) is localized to the `[Nucleus](/details-pathway/GO:0005634)`, where it associates with `[Chromatin](/details-pathway/GO:0000785)` to exert its regulatory effects. - **Biological Processes:** The gene is a key participant in the Reactome pathway `[Activation of hox genes during differentiation](/details-pathway/R-HSA-5619507)`, a fundamental process in developmental biology. This role is complemented by its involvement in `[Embryonic skeletal system development](/details-pathway/GO:0048706)` and `[Neuron differentiation](/details-pathway/GO:0030182)`. An intriguing annotated function is its involvement in the `[Sensory perception of pain](/details-pathway/GO:0019233)`, which aligns with its expression in peripheral nervous system neurons. ## Research Directions The specific expression pattern and known functions of [HOXD1](/details-gene/3231) suggest several avenues for future investigation, particularly concerning its role in tissue homeostasis and disease. **Proposed Hypotheses:** 1. Given its high and specific expression in terminally differentiated epithelial cells of the reproductive and respiratory tracts, [HOXD1](/details-gene/3231) may be essential for maintaining the transcriptional programs that define the identity and function of these cells in adult tissues. Its loss could lead to de-differentiation or impaired tissue repair. 2. Based on its expression in `[peripheral nervous system neuron](/details-cell/CL2000032)` and its link to `[Sensory perception of pain](/details-pathway/GO:0019233)`, [HOXD1](/details-gene/3231) may regulate the expression of key ion channels, neuropeptides, or receptors involved in nociceptive signaling pathways. **Experimental Approach:** To test the first hypothesis regarding the role of [HOXD1](/details-gene/3231) in maintaining epithelial identity, one could utilize an *in vitro* air-liquid interface (ALI) culture of primary human bronchial epithelial cells. A loss-of-function study could be performed using CRISPR interference (CRISPRi) to specifically repress [HOXD1](/details-gene/3231) transcription. The impact of its knockdown on cellular identity and function could be assessed by single-cell RNA sequencing (scRNA-seq) to identify shifts in cell populations (e.g., loss of ciliated or secretory cells) and by functional assays such as measuring ciliary beat frequency or mucus production. **Therapeutic Potential:** As a transcription factor, [HOXD1](/details-gene/3231) is a challenging direct therapeutic target. However, its high specificity in certain epithelial tissues suggests its dysregulation could be implicated in diseases such as chronic obstructive pulmonary disease (COPD) or cancers originating from these tissues (e.g., lung adenocarcinoma, ovarian cancer). If [HOXD1](/details-gene/3231) is found to be an oncogenic driver in these contexts, therapeutic strategies would likely focus on the inhibition of its key downstream targets or upstream activating pathways, rather than direct inhibition of the protein itself.

Genular Protein ID: 2047165387

Symbol: HXD1_HUMAN

Name: Homeobox protein Hox-D1

UniProtKB Accession Codes:

Q9GZZ0 B2RAB4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 GO 10 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 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: 11455954

Title: Isolation and characterization of the human homeobox gene HOX D1.

PubMed ID: 11455954

DOI: 10.1023/a:1011048931477

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

Sequence Information:

  • Length: 328
  • Mass: 34093
  • Checksum: 1B9EBBF4E2DA0301
  • Sequence:
    • MSSYLEYVSC SSSGGVGGDV LSLAPKFCRS DARPVALQPA FPLGNGDGAF VSCLPLAAAR 
PSPSPPAAPA RPSVPPPAAP QYAQCTLEGA YEPGAAPAAA AGGADYGFLG SGPAYDFPGV 
LGRAADDGGS HVHYATSAVF SGGGSFLLSG QVDYAAFGEP GPFPACLKAS ADGHPGAFQT 
ASPAPGTYPK SVSPASGLPA AFSTFEWMKV KRNASKKGKL AEYGAASPSS AIRTNFSTKQ 
LTELEKEFHF NKYLTRARRI EIANCLHLND TQVKIWFQNR RMKQKKRERE GLLATAIPVA 
PLQLPLSGTT PTKFIKNPGS PSQSQEPS

Genular Protein ID: 1227728381

Symbol: Q96CA4_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q96CA4

Database IDs:

ARBA 6 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 GO 3 Gene3D 1 InterPro 5 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 1 PROSITE 3 PROSITE-ProRule 1 Pfam 1 RefSeq 1 RuleBase 1 SAM 1 SMART 1 SUPFAM 1

Citations:

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

Sequence Information:

  • Length: 328
  • Mass: 34083
  • Checksum: 24A1B8072CEBE113
  • Sequence:
    • MSSYLEYVSC SSSGGVGGDV LSLAPKFCRS DARPVALQPA FPLGNGDGAF VSCLPLAAAR 
PSPSPPAAPA RPSVPPPAAP QYAQCTLEGA YEPGAAPAAA AGGADYGFLG SGPAYDFPGV 
LGRAADDGGS HVHYATSAVF SGGGSFLLSG QVDYAAFGEP GPFSACLKAS ADGHPGAFQT 
ASPAPGTYPK SVSPASGLPA AFSTFEWMKV KRNASKKGKL AEYGAASPSS AIRTNFSTKQ 
LTELEKEFHF NKYLTRARRI EIANCLHLND TQVKIWFQNR RMKQKKRERE GLLATAIPVA 
PLQLPLSGTT PTKFIKNPGS PSQSQEPS