1. Gene Aliases

Aqp7, AQPap, AQP7L, AQP9, Aquaglyceroporin-7, Aquaporin Adipose, Aquaporin-7, Aquaporin-7-Like, GLYCQTL, AQPAP, AQP-7

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=AQP7&keywords=Aqp7].

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

glycerol transmembrane transport [The directed movement of glycerol across a membrane. Glycerol is 1,2,3-propanetriol, a sweet, hygroscopic, viscous liquid, widely distributed in nature as a constituent of many lipids. GO:0015793]

renal water absorption [A renal system process in which water is taken up from the collecting ducts and proximal and distal loops of the nephron. In non-mammalian species, absorption may occur in related structures. GO:0070295]

response to xenobiotic stimulus [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organim exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical. GO:0009410]

spermatogenesis [The developmental process by which male germ line stem cells self-renewal or give rise to successive cell types resulting in the development of a spermatozoa. GO:0007283]

urea transmembrane transport [The process in which urea, the water-soluble compound H2N-CO-NH2, is transported from one side of a membrane to the other by means of some agent such as a transporter or pore. Note that this term is not intended for use in annotating lateral movement within membranes. GO:0071918]

urea transport [The directed movement of urea into, out of or within the cell. Urea is the water-soluble compound H2N-CO-NH2. GO:0015840]

water transport [The directed movement of water (H2O) into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. GO:0006833]

MSigDB Signatures:

CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_DN: Genes down-regulated in hepatoblastoma (HB) tumors as compared with non-tumor (NT) adjacent tissue. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_DN.html]

KEGG_PPAR_SIGNALING_PATHWAY: PPAR signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_PPAR_SIGNALING_PATHWAY.html]

WP_PPAR_SIGNALING_PATHWAY: PPAR signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_PPAR_SIGNALING_PATHWAY.html]

REACTOME_AQUAPORIN_MEDIATED_TRANSPORT: Aquaporin-mediated transport [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_AQUAPORIN_MEDIATED_TRANSPORT.html]

REACTOME_TRANSPORT_OF_SMALL_MOLECULES: Transport of small molecules [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_TRANSPORT_OF_SMALL_MOLECULES.html]

REACTOME_PASSIVE_TRANSPORT_BY_AQUAPORINS: Passive transport by Aquaporins [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_PASSIVE_TRANSPORT_BY_AQUAPORINS.html]

WP_THYROID_HORMONES_PRODUCTION_AND_PERIPHERAL_DOWNSTREAM_SIGNALING_EFFECTS: Thyroid hormones production and peripheral downstream signaling effects [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_THYROID_HORMONES_PRODUCTION_AND_PERIPHERAL_DOWNSTREAM_SIGNALING_EFFECTS.html]

7. Gene Descriptions

NCBI Gene Summary: This gene encodes a member of the aquaporin family of water-selective membrane channels. The encoded protein localizes to the plasma membrane and allows movement of water, glycerol and urea across cell membranes. This gene is highly expressed in the adipose tissue where the encoded protein facilitates efflux of glycerol. In the proximal straight tubules of kidney, the encoded protein is localized to the apical membrane and prevents excretion of glycerol into urine. The encoded protein is present in spermatids, as well as in the testicular and epididymal spermatozoa suggesting an important role in late spermatogenesis. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. This gene is located adjacent to a related aquaporin gene on chromosome 9. Multiple pseudogenes of this gene have been identified. [provided by RefSeq, Dec 2015]

GeneCards Summary: AQP7 (Aquaporin 7) is a Protein Coding gene. Diseases associated with AQP7 include Glycerol Quantitative Trait Locus and Hepatocellular Carcinoma. Among its related pathways are Aquaporin-mediated transport and Nanog in Mammalian ESC Pluripotency. Gene Ontology (GO) annotations related to this gene include transporter activity and glycerol channel activity. An important paralog of this gene is AQP7B.

UniProtKB/Swiss-Prot Summary: Forms a channel that mediates water and glycerol transport across cell membranes at neutral pH [PMID: 9405233, PMID: 11952783, PMID: 30423801, PMID: 30420639]. The channel is also permeable to urea [PMID: 9405233]. Plays an important role in body energy homeostasis under conditions that promote lipid catabolism, giving rise to glycerol and free fatty acids. Mediates glycerol export from adipocytes. After release into the blood stream, glycerol is used for gluconeogenesis in the liver to maintain normal blood glucose levels and prevent fasting hypoglycemia. Required for normal glycerol reabsorption in the kidney.

8. Cellular Location of Gene Product

Predicted location: Membrane, Intracellular (different isoforms) [https://www.proteinatlas.org/ENSG00000165269/subcellular]

9. Mechanistic Information

Summary

AQP7 is primarily involved in mediating the transport of glycerol across cell membranes, a critical process in maintaining energy homeostasis and glucose levels [CS: 10]. In healthy conditions, AQP7 facilitates the release of glycerol from adipocytes into the bloodstream, where it is used for gluconeogenesis in the liver, thus helping to maintain normal blood glucose levels [CS: 10]. Liver toxicity or damage could potentially trigger the overexpression of AQP7 as a compensatory response to maintain metabolic homeostasis, particularly in the context of disrupted glycerol and glucose metabolism [CS: 7]. When the liver is damaged or stressed, its ability to perform normal metabolic functions, such as gluconeogenesis and lipid metabolism, can be impaired [CS: 9]. This impairment can lead to metabolic imbalances, including altered glucose levels and lipid accumulation [CS: 9]. In such a scenario, the body may respond by upregulating AQP7 to facilitate the increased transport of glycerol from adipocytes into the bloodstream, provide an enhanced supply of glycerol to the liver, supporting gluconeogenesis and helping to maintain normal blood glucose levels [CS: 7]. This increased glycerol supply is particularly vital when the liver's gluconeogenic capacity is compromised due to toxicity or damage [CS: 7]. By overexpressing AQP7, the body attempts to counteract the impaired metabolic functions of the damaged liver, striving to maintain energy balance and prevent complications like hypoglycemia [CS: 7].

The observed downregulation of AQP7 in the context of liver diseases, such as hepatocellular carcinoma (HCC), impairs this glycerol transport mechanism [CS: 9]. Reduced AQP7 expression means less glycerol is available for gluconeogenesis [CS: 9]. This potentially disrupts glucose homeostasis and exacerbates the energy deficit typically associated with liver diseases [CS: 8]. Furthermore, the decreased AQP7 expression in the liver could lead to an accumulation of glycerol in adipocytes, contributing to metabolic imbalances [CS: 8]. This scenario is particularly detrimental in liver pathologies, as the liver's ability to regulate metabolism, including gluconeogenesis and lipid catabolism, is already compromised [CS: 9].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: adipose tissue, breast, heart muscle (tissue enhanced) [https://www.proteinatlas.org/ENSG00000165269/tissue]

Cell type enchanced: adipocytes, cardiomyocytes, early spermatids, proximal enterocytes, proximal tubular cells (cell type enhanced) [https://www.proteinatlas.org/ENSG00000165269/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest