Details for: HOXD9

Gene ID: 3235

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: HOXD9

Ensembl ID: ENSG00000128709

Description: homeobox D9

Cell Significance Landscape

Associated with

  • Adult locomotory behavior
    (GO:0008344)
  • Anterior/posterior pattern specification
    (GO:0009952)
  • Chromatin
    (GO:0000785)
  • Dna-binding transcription factor activity
    (GO:0003700)
  • Dna-binding transcription factor activity, rna polymerase ii-specific
    (GO:0000981)
  • Dna-binding transcription repressor activity, rna polymerase ii-specific
    (GO:0001227)
  • Dna-templated transcription
    (GO:0006351)
  • Embryonic forelimb morphogenesis
    (GO:0035115)
  • Embryonic skeletal system morphogenesis
    (GO:0048704)
  • Hindlimb morphogenesis
    (GO:0035137)
  • Mammary gland development
    (GO:0030879)
  • Negative regulation of transcription by rna polymerase ii
    (GO:0000122)
  • Nucleolus
    (GO:0005730)
  • Nucleoplasm
    (GO:0005654)
  • Nucleus
    (GO:0005634)
  • Peripheral nervous system neuron development
    (GO:0048935)
  • Positive regulation of transcription by rna polymerase ii
    (GO:0045944)
  • Proximal/distal pattern formation
    (GO:0009954)
  • Regulation of transcription by rna polymerase ii
    (GO:0006357)
  • Rna polymerase ii cis-regulatory region sequence-specific dna binding
    (GO:0000978)
  • Rna polymerase ii transcription regulatory region sequence-specific dna binding
    (GO:0000977)
  • Sequence-specific double-stranded dna binding
    (GO:1990837)
  • Single fertilization
    (GO:0007338)
  • Skeletal muscle tissue development
    (GO:0007519)

Significant Cells

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

  • blood vessel endothelial cell CL0000071
    CSI 4.81
    rCSI 9.97%
    PRS 98.05
  • endothelial cell of uterus CL0009095
    CSI 4.23
    rCSI 30.96%
    PRS 99.45
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 2.22
    rCSI 5.73%
    PRS 98.04
  • renal principal cell CL0005009
    CSI 2.01
    rCSI 5.22%
    PRS 98.41
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.49
    rCSI 3.77%
    PRS 97.27
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 1.29
    rCSI 13.7%
    PRS 96.96

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 [HOXD9](/details-gene/3235) is a protein-coding gene located on chromosome 2 that encodes Homeobox protein Hox-D9, a member of the homeobox family of DNA-binding transcription factors. These proteins are critical regulators of embryonic development. Functional annotations strongly link [HOXD9](/details-gene/3235) to morphogenesis, particularly anterior/posterior pattern specification ([GO:0009952](https://www.ebi.ac.uk/QuickGO/term/GO:0009952)), skeletal system development ([GO:0048704](https://www.ebi.ac.uk/QuickGO/term/GO:0048704)), and limb formation ([GO:0035115](https://www.ebi.ac.uk/QuickGO/term/GO:0035115)) [Link](https://pubmed.ncbi.nlm.nih.gov/2568311/). **Overall**, expression data reveals its high significance not only in developmental contexts but also in specific adult cell types, most notably in `[blood vessel endothelial cell](/details-cell/CL0000071)` and various specialized epithelial cells of the kidney, suggesting a role in maintaining the function and identity of these tissues. Clinically, it is associated with the OMIM entry for homeobox D cluster ([142982](https://omim.org/entry/142982)). ## Cellular Roles and Expression Landscape The expression profile of [HOXD9](/details-gene/3235) highlights its specialized function in distinct adult cell lineages. **Overall**, the gene shows the highest significance in `[blood vessel endothelial cell](/details-cell/CL0000071)` (CSI: 4.81) and `[endothelial cell of uterus](/details-cell/CL0009095)` (CSI: 4.23), indicating it may serve as a key transcriptional regulator defining the identity or function of the vascular endothelium. Beyond its role in the vasculature, [HOXD9](/details-gene/3235) demonstrates a remarkably specific expression pattern within the renal system. It is a significant marker for several types of kidney epithelial cells, including `[kidney loop of Henle thin ascending limb epithelial cell](/details-cell/CL1001107)` (CSI: 2.22), `[renal principal cell](/details-cell/CL0005009)` (CSI: 2.01), and `[kidney connecting tubule epithelial cell](/details-cell/CL1000768)` (CSI: 1.49). This compartmentalized expression suggests a potential role in modulating the highly specialized transport and homeostatic functions characteristic of these different segments of the nephron. The specific and high-level expression in these endothelial and renal cell types points towards a continued, non-developmental role for [HOXD9](/details-gene/3235) in adult tissue homeostasis. ## Pathways and Molecular Function [HOXD9](/details-gene/3235) functions as a sequence-specific DNA-binding transcription factor, a role supported by its molecular function annotations, including `[DNA-binding transcription factor activity, RNA polymerase II-specific](/details-cell/GO:0000981)` and `[RNA polymerase II cis-regulatory region sequence-specific DNA binding](/details-cell/GO:0000978)`. As a member of the HOX gene family, it can act as both a transcriptional activator ([GO:0045944](https://www.ebi.ac.uk/QuickGO/term/GO:0045944)) and repressor ([GO:0000122](https://www.ebi.ac.uk/QuickGO/term/GO:0000122)), allowing for fine-tuned control of downstream gene expression programs [Link](https://doi.org/10.1002/j.1460-2075.1991.tb04996.x). Its localization to the nucleus ([GO:0005634](https://www.ebi.ac.uk/QuickGO/term/GO:0005634)) and chromatin ([GO:0000785](https://www.ebi.ac.uk/QuickGO/term/GO:0000785)) is consistent with this function. The biological processes associated with [HOXD9](/details-gene/3235) are predominantly developmental. It is a key player in `[anterior/posterior pattern specification](/details-cell/GO:0009952)` and the morphogenesis of multiple structures, including forelimbs ([GO:0035115](https://www.ebi.ac.uk/QuickGO/term/GO:0035115)), hindlimbs ([GO:0035137](https://www.ebi.ac.uk/QuickGO/term/GO:0035137)), and the embryonic skeletal system ([GO:0048704](https://www.ebi.ac.uk/QuickGO/term/GO:0048704)). While these functions are well-established, its significant expression in adult endothelial and kidney cells suggests these fundamental transcriptional programs may be repurposed to maintain cellular identity and function post-development. ## Research Directions The pronounced and specific expression of [HOXD9](/details-gene/3235) in adult vascular and renal cells, beyond its canonical role in embryogenesis, presents intriguing avenues for future research. Understanding its function in these terminally differentiated tissues could reveal novel mechanisms of tissue homeostasis. Based on the available data, we propose the following testable hypotheses: 1. In `[blood vessel endothelial cell](/details-cell/CL0000071)`, [HOXD9](/details-gene/3235) acts as a master regulator that maintains vascular quiescence and integrity by controlling the expression of cell adhesion molecules and anti-angiogenic factors. Its dysregulation could contribute to pathological angiogenesis or vascular permeability. 2. The segment-specific expression of [HOXD9](/details-gene/3235) in kidney tubules indicates it dictates the unique functional identity of each epithelial cell type, such as by directly regulating the transcription of specific ion transporters (e.g., aquaporins, sodium channels) critical for renal filtration and reabsorption. To test the first hypothesis regarding its role in endothelial cells, a key experiment would involve the selective knockout of [HOXD9](/details-gene/3235) in human endothelial cell lines (e.g., HUVECs) using a CRISPR-Cas9 system. Subsequent RNA-sequencing would identify downstream transcriptional targets, while functional assays, such as electrical cell-substrate impedance sensing (ECIS) for barrier function and in vitro tube formation assays, would directly assess the impact of its loss on vascular integrity and angiogenic potential. **Therapeutic Potential** As an intracellular transcription factor, [HOXD9](/details-gene/3235) represents a challenging therapeutic target for direct inhibition with small molecules. However, its high specificity in certain adult cell types suggests it could be an important biomarker. For instance, aberrant [HOXD9](/details-gene/3235) expression may mark specific subtypes of endothelial-derived tumors (angiosarcomas) or renal cell carcinomas. In such contexts, downstream cell surface proteins regulated by [HOXD9](/details-gene/3235) could represent more tractable targets for antibody-based therapies. Therefore, its immediate therapeutic relevance is more likely in diagnostics and patient stratification rather than as a direct drug target.

Genular Protein ID: 54322379

Symbol: HXD9_HUMAN

Name: Homeobox protein Hox-D9

UniProtKB Accession Codes:

P28356 Q86ST1

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 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 GO 24 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 1 PRO 1 PROSITE 2 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 jPOST 1 neXtProt 1

Citations:

PubMed ID: 1756725

Title: HOX4 genes encode transcription factors with potential auto- and cross-regulatory capacities.

PubMed ID: 1756725

DOI: 10.1002/j.1460-2075.1991.tb04996.x

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: 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: 2568311

Title: Complementary homeo protein gradients in developing limb buds.

PubMed ID: 2568311

DOI: 10.1101/gad.3.5.641

PubMed ID: 2574852

Title: The human HOX gene family.

PubMed ID: 2574852

DOI: 10.1093/nar/17.24.10385

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 11857506

Title: Complete mutation analysis panel of the 39 human HOX genes.

PubMed ID: 11857506

DOI: 10.1002/tera.10009

Sequence Information:

  • Length: 352
  • Mass: 36495
  • Checksum: ECBFE68B48C0F532
  • Sequence:
    • MLGGSAGRLK MSSSGTLSNY YVDSLIGHEG DEVFAARFGP PGPGAQGRPA GVADGPAATA 
AEFASCSFAP RSAVFSASWS AVPSQPPAAA AMSGLYHPYV PPPPLAASAS EPGRYVRSWM 
EPLPGFPGGA GGGGGGGGGG PGRGPSPGPS GPANGRHYGI KPETRAAPAP ATAASTTSSS 
STSLSSSSKR TECSVARESQ GSSGPEFSCN SFLQEKAAAA TGGTGPGAGI GAATGTGGSS 
EPSACSDHPI PGCSLKEEEK QHSQPQQQQL DPNNPAANWI HARSTRKKRC PYTKYQTLEL 
EKEFLFNMYL TRDRRYEVAR ILNLTERQVK IWFQNRRMKM KKMSKEKCPK GD