Details for: AQP9

Gene ID: 366

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: AQP9

Ensembl ID: ENSG00000103569

Description: aquaporin 9

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • myeloid leukocyte CL0000766
    CSI 11.2
    rCSI 10.33%
    PRS 85.4
  • granulocyte CL0000094
    CSI 8.93
    rCSI 13.65%
    PRS 90.06
  • lung macrophage CL1001603
    CSI 7.31
    rCSI 16.32%
    PRS 90.29
  • neutrophil CL0000775
    CSI 6.67
    rCSI 37.34%
    PRS 84.03
  • alternatively activated macrophage CL0000890
    CSI 6.09
    rCSI 7.65%
    PRS 91.79
  • intermediate monocyte CL0002393
    CSI 4.33
    rCSI 6.53%
    PRS 88.92
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 3.98
    rCSI 5.22%
    PRS 92.71
  • midzonal region hepatocyte CL0019028
    CSI 3.65
    rCSI 8.57%
    PRS 83.05
  • Kupffer cell CL0000091
    CSI 3.65
    rCSI 8.34%
    PRS 84.97
  • elicited macrophage CL0000861
    CSI 3.49
    rCSI 3.2%
    PRS 90.69
  • alveolar macrophage CL0000583
    CSI 3.47
    rCSI 5.72%
    PRS 87.45
  • monocyte CL0000576
    CSI 3.25
    rCSI 5.88%
    PRS 87.45
  • hepatocyte CL0000182
    CSI 2.82
    rCSI 5.05%
    PRS 83.23
  • Mueller cell CL0000636
    CSI 2.79
    rCSI 6.37%
    PRS 76.07
  • CD14-positive monocyte CL0001054
    CSI 2.78
    rCSI 3.46%
    PRS 91.64
  • lung interstitial macrophage CL4033043
    CSI 2.74
    rCSI 6.15%
    PRS 93.47
  • mononuclear phagocyte CL0000113
    CSI 2.56
    rCSI 5.63%
    PRS 87.29
  • hepatic stellate cell CL0000632
    CSI 2.55
    rCSI 9.54%
    PRS 77.21
  • periportal region hepatocyte CL0019026
    CSI 2.37
    rCSI 9.22%
    PRS 82.46
  • centrilobular region hepatocyte CL0019029
    CSI 1.96
    rCSI 5.11%
    PRS 81.62
  • intrahepatic cholangiocyte CL0002538
    CSI 1.71
    rCSI 4.1%
    PRS 86.46
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 0.54
    rCSI 3.24%
    PRS 92.71

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

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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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
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    • 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 [AQP9](/details-gene/366) is a protein-coding gene located on chromosome 15 that encodes Aquaporin-9, a member of the aquaporin family of integral membrane proteins. These proteins form channels that facilitate the transport of water and small neutral solutes across the plasma membrane. [AQP9](/details-gene/366) is classified as an aquaglyceroporin due to its high permeability to water, urea, and glycerol, but not to larger molecules [Link](https://doi.org/10.1006/bbrc.1998.8252), [Link](https://doi.org/10.1152/ajprenal.1999.277.5.f685). Expression data highlight its prominent role in the hematopoietic system, with exceptionally high significance in [myeloid leukocyte](/details-cell/CL0000766)s, including [granulocyte](/details-cell/CL0000094)s, various macrophage populations, and [monocyte](/details-cell/CL0000576)s. It is also significantly expressed in [hepatocyte](/details-cell/CL0000182)s, suggesting a dual function in both innate immunity and liver metabolism. ## Cellular Roles and Expression Landscape The expression profile of [AQP9](/details-gene/366) strongly indicates a primary function within the innate immune system and liver. **Overall**, the gene shows the highest significance in cells of the myeloid lineage. It is a top marker for [myeloid leukocyte](/details-cell/CL0000766) (CSI: 11.20) and [granulocyte](/details-cell/CL0000094) (CSI: 8.93), with particularly high scores in [neutrophil](/details-cell/CL0000775)s (CSI: 6.67). This suggests a fundamental role for [AQP9](/details-gene/366) in the function of these first-responder immune cells, which could involve osmoregulation during phagocytosis or migration. Furthermore, [AQP9](/details-gene/366) is highly significant across a spectrum of macrophage and monocyte populations. These include resident tissue macrophages like [lung macrophage](/details-cell/CL1001603) (CSI: 7.31) and [Kupffer cell](/details-cell/CL0000091) (CSI: 3.65), as well as functionally distinct subsets such as [alternatively activated macrophage](/details-cell/CL0000890) (CSI: 6.09) and various [monocyte](/details-cell/CL0000576) types. This broad yet specific expression pattern within the myeloid compartment suggests that the transport of water, glycerol, or urea via [AQP9](/details-gene/366) is a conserved requirement for the metabolic and functional activities of these phagocytic cells. Outside of the immune system, [AQP9](/details-gene/366) is also a significant marker for [hepatocyte](/details-cell/CL0000182)s (CSI: 2.82), particularly [midzonal region hepatocyte](/details-cell/CL0019028)s (CSI: 3.65). This is consistent with its role in hepatic glycerol metabolism, where it facilitates the uptake of glycerol for gluconeogenesis. The absence of high significance in lymphoid, neuronal, or epithelial cell types in the provided data underscores its specialized function primarily in myeloid and hepatic cells. ## Pathways and Molecular Function The functional annotations for [AQP9](/details-gene/366) align precisely with its identity as a versatile channel protein and its observed cellular expression pattern. Its molecular functions are dominated by channel and transporter activities, including [water channel activity](/details-cell/GO:0015250), [glycerol channel activity](/details-cell/GO:0015254), and [urea transmembrane transporter activity](/details-cell/GO:0015204). These functions are integral to several key biological processes. The high expression in [hepatocyte](/details-cell/CL0000182)s is directly explained by its involvement in [glycerol transmembrane transport](/details-cell/GO:0015793) and its role in the Reactome pathway [Transport of glycerol from adipocytes to the liver by aquaporins](/details-cell/R-HSA-432030). This process is vital for maintaining glucose homeostasis. In [myeloid leukocyte](/details-cell/CL0000766)s, the transport of water and solutes is critical for maintaining cell volume and osmotic balance, especially during inflammatory responses and phagocytosis. Furthermore, glycerol transport may be linked to cellular energy metabolism, as glycerol is a substrate for ATP production, which is essential for the high metabolic demands of activated immune cells. The gene's role in [purine nucleobase transmembrane transport](/details-cell/GO:1904823) could also be relevant for immune cell function, as purines are important signaling molecules in inflammation. The collective evidence places [AQP9](/details-gene/366) as a key facilitator of small molecule transport, supporting the metabolic and homeostatic needs of specific, highly active cell types. ## Research Directions The specific expression pattern of [AQP9](/details-gene/366) in myeloid cells and hepatocytes, combined with its function as a transporter of key metabolic substrates, opens several avenues for future research and therapeutic development. ### Proposed Hypotheses: 1. **Metabolic Regulation of Macrophage Function:** Given its high expression in diverse macrophage populations, including [alternatively activated macrophage](/details-cell/CL0000890)s, we hypothesize that [AQP9](/details-gene/366)-mediated glycerol uptake is a critical metabolic checkpoint that fuels the specific functional polarization of macrophages. Inhibition of [AQP9](/details-gene/366) may impair M2-like polarization by limiting a key substrate for oxidative phosphorylation, thereby altering inflammatory outcomes. 2. **Neutrophil Effector Function and Cell Volume Regulation:** The high significance of [AQP9](/details-gene/366) in [neutrophil](/details-cell/CL0000775)s suggests a role beyond simple homeostasis. We hypothesize that [AQP9](/details-gene/366) is essential for rapid cell volume changes required during diapedesis and chemotaxis, and that its transport of water and urea is critical for regulating intracellular osmolarity during the formation of neutrophil extracellular traps (NETs). ### Key Experimental Approach: To test the hypothesis regarding macrophage polarization, a myeloid-specific knockout of [AQP9](/details-gene/366) could be generated in mice (e.g., using a Lyz2-Cre driver). Bone marrow-derived macrophages (BMDMs) from these knockout mice and wild-type littermates would be cultured and polarized towards M1 (LPS/IFN-γ) and M2 (IL-4/IL-13) phenotypes. The impact of [AQP9](/details-gene/366) deletion would be assessed by: - **Metabolic analysis:** Using techniques like Seahorse XF analysis to measure the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) to determine reliance on oxidative phosphorylation versus glycolysis. - **Functional assays:** Quantifying phagocytic capacity, nitric oxide production (for M1), and arginase activity (for M2). - **Transcriptomic and proteomic profiling:** Using RNA-seq and mass spectrometry to identify changes in the expression of canonical M1/M2 markers and associated signaling pathways. ### Therapeutic Potential: As a plasma membrane channel protein, [AQP9](/details-gene/366) is an accessible therapeutic target. Its high expression on myeloid cells suggests it could be targeted to modulate innate immune responses. In inflammatory diseases characterized by excessive macrophage or neutrophil activity (e.g., rheumatoid arthritis, sepsis, or atherosclerosis), a specific **inhibitor** of [AQP9](/details-gene/366) could potentially reduce immune cell activation by restricting metabolic substrate availability, thereby dampening the inflammatory cascade. However, the high expression in hepatocytes presents a significant risk for off-target effects on liver metabolism, which would need to be carefully evaluated. The development of inhibitors that selectively target [AQP9](/details-gene/366) in specific cellular contexts or inflamed tissues would be a critical step for therapeutic translation.

Genular Protein ID: 3171020758

Symbol: AQP9_HUMAN

Name: Aquaporin-9

UniProtKB Accession Codes:

O43315 Q9NP32

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 DrugBank 1 EMBL 6 Ensembl 1 ExpressionAtlas 1 GO 18 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9514918

Title: Cloning and functional expression of a new aquaporin (AQP9) abundantly expressed in the peripheral leukocytes permeable to water and urea, but not to glycerol.

PubMed ID: 9514918

DOI: 10.1006/bbrc.1998.8252

PubMed ID: 10564231

Title: Functional and molecular characterization of the human neutral solute channel aquaporin-9.

PubMed ID: 10564231

DOI: 10.1152/ajprenal.1999.277.5.f685

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

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: 30420639

Title: Human adipose glycerol flux is regulated by a pH gate in AQP10.

PubMed ID: 30420639

DOI: 10.1038/s41467-018-07176-z

Sequence Information:

  • Length: 295
  • Mass: 31431
  • Checksum: B3B416CD9F1F9CAF
  • Sequence:
    • MQPEGAEKGK SFKQRLVLKS SLAKETLSEF LGTFILIVLG CGCVAQAILS RGRFGGVITI 
NVGFSMAVAM AIYVAGGVSG GHINPAVSLA MCLFGRMKWF KLPFYVGAQF LGAFVGAATV 
FGIYYDGLMS FAGGKLLIVG ENATAHIFAT YPAPYLSLAN AFADQVVATM ILLIIVFAIF 
DSRNLGAPRG LEPIAIGLLI IVIASSLGLN SGCAMNPARD LSPRLFTALA GWGFEVFRAG 
NNFWWIPVVG PLVGAVIGGL IYVLVIEIHH PEPDSVFKTE QSEDKPEKYE LSVIM

Genular Protein ID: 3434742404

Symbol: H0YK62_HUMAN

Name: N/A

UniProtKB Accession Codes:

H0YK62

Database IDs:

ARBA 6 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 2 ExpressionAtlas 1 GO 3 Gene3D 1 GeneTree 1 HGNC 1 HOGENOM 1 InterPro 5 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OrthoDB 1 PANTHER 2 PRINTS 2 PROSITE 1 PeptideAtlas 2 Pfam 1 Proteomes 2 ProteomicsDB 2 RefSeq 1 RuleBase 1 SAM 1 SMR 1 SUPFAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

Sequence Information:

  • Length: 230
  • Mass: 24546
  • Checksum: 8CAD0CA08EC56EFC
  • Sequence:
    • MAVAMAIYVA GGVSGGHINP AVSLAMCLFG RMKWFKLPFY VGAQFLGAFV GAATVFGIYY 
DGLMSFAGGK LLIVGENATA HIFATYPAPY LSLANAFADQ VVATMILLII VFAIFDSRNL 
GAPRGLEPIA IGLLIIVIAS SLGLNSGCAM NPARDLSPRL FTALAGWGFE VFRAGNNFWW 
IPVVGPLVGA VIGGLIYVLV IEIHHPEPDS VFKTEQSEDK PEKYELSVIM