1. Gene Aliases

Rat and mouse Akr1b8 has three closely related genes in human: AKR1B10, AKR1B15 and AKR1B1. Annotation of human-related studies was based on AKR1B10.

Aldo-Keto Reductase Family 1 Member B10, ARL-1, Aldose Reductase-Related Protein, Small Intestine Reductase, AKR1B12, AKR1B11, ARL1, HIS, HSI, Aldo-Keto Reductase Family 1 Member B11 (Aldose Reductase-Like), Aldo-Keto Reductase Family 1 Member B10 (Aldose Reductase), Aldose Reductase-Like Peptide, Aldose Reductase-Like 1, SI Reductase, ALDRLn, HARP, ARP, Aldose Reductase-Like

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=AKR1B10&keywords=AKR1B10]

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

5. Links to Gene Databases

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

Pathways:

GO terms:

Gene Akr1b8 lacks GO biological process annotations [https://rgd.mcw.edu/rgdweb/report/gene/main.html?id=708475#geneOntologyAnnotationsCurator]

MSigDB Signatures:

CHIANG_LIVER_CANCER_SUBCLASS_POLYSOMY7_DN: Marker genes down-regulated in the 'chromosome 7 polysomy' subclass of hepatocellular carcinoma (HCC); characterized by polysomy of chromosome 7 and by a lack of gains of chromosome 8q. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/CHIANG_LIVER_CANCER_SUBCLASS_POLYSOMY7_DN.html]

WP_METAPATHWAY_BIOTRANSFORMATION_PHASE_I_AND_II: Metapathway biotransformation Phase I and II [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_METAPATHWAY_BIOTRANSFORMATION_PHASE_I_AND_II.html]

LIAO_HAVE_SOX4_BINDING_SITES: Genes up-regulated in the samples with intrahepatic metastatic hepatocellular carcinoma (HCC) vs primary HCC that also have putative binding sites for SOX4 [GeneID=6659]. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/LIAO_HAVE_SOX4_BINDING_SITES.html]

REACTOME_METABOLISM_OF_FAT_SOLUBLE_VITAMINS: Metabolism of fat-soluble vitamins [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_METABOLISM_OF_FAT_SOLUBLE_VITAMINS.html]

LIAO_METASTASIS: Genes up-regulated in the samples with intrahepatic metastatic hepatocellular carcinoma (HCC) vs primary HCC. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/LIAO_METASTASIS.html]

KEGG_LINOLEIC_ACID_METABOLISM: Linoleic acid metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_LINOLEIC_ACID_METABOLISM.html]

REACTOME_METABOLISM_OF_VITAMINS_AND_COFACTORS: Metabolism of vitamins and cofactors [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_METABOLISM_OF_VITAMINS_AND_COFACTORS.html]

KEGG_BUTANOATE_METABOLISM: Butanoate metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_BUTANOATE_METABOLISM.html]

GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_GREEN_UP: Genes from the green module which are up-regulated in HAEC cells (primary aortic endothelium) after exposure to the oxidized 1-palmitoyl-2-arachidonyl-sn-3-glycerophosphorylcholine (oxPAPC). [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_GREEN_UP.html]

KEGG_FRUCTOSE_AND_MANNOSE_METABOLISM: Fructose and mannose metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_FRUCTOSE_AND_MANNOSE_METABOLISM.html]

IBRAHIM_NRF1_UP: Genes up-regulated in HEK293T cells overexpressing FLAG-NRF1 [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/IBRAHIM_NRF1_UP.html]

IBRAHIM_NRF2_UP: Genes up-regulated in HEK293T cells overexpressing FLAG-NRF2 [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/IBRAHIM_NRF2_UP.html]

REACTOME_SENSORY_PERCEPTION: Sensory Perception [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SENSORY_PERCEPTION.html]

PUIFFE_INVASION_INHIBITED_BY_ASCITES_UP: Genes up-regulated in OV-90 cells (ovarian cancer) exposed to ascites which inhibited invasion. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/PUIFFE_INVASION_INHIBITED_BY_ASCITES_UP.html]

KAN_RESPONSE_TO_ARSENIC_TRIOXIDE: Genes changed in U373-MG cells (malignant glioma) upon treatment with arsenic trioxide [PubChem=14888], a chemical that can cause autophagic cell death. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KAN_RESPONSE_TO_ARSENIC_TRIOXIDE.html]

MIYAGAWA_TARGETS_OF_EWSR1_ETS_FUSIONS_UP: Genes commonly up-regulated in UET-13 cells (mesenchymal progenitor) by expression of EWSR1 [GeneID=2130] fusions with ETS transcription factors FLI1 and ERG [GeneID=2313 ,2078]. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/MIYAGAWA_TARGETS_OF_EWSR1_ETS_FUSIONS_UP.html]

FARMER_BREAST_CANCER_APOCRINE_VS_LUMINAL: Genes which best discriminate between two groups of breast cancer according to the status of ESR1 and AR [GeneID=2099;367]: apocrine (ESR1- AR+) and luminal (ESR1+ AR+). [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/FARMER_BREAST_CANCER_APOCRINE_VS_LUMINAL.html]

MOOTHA_PGC: Genes up-regulated in differentiating C2C12 cells (myoblasts) upon expression of PPARGC1A [GeneID=10891] off an adenoviral vector. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/MOOTHA_PGC.html]

JINESH_BLEBBISHIELD_TRANSFORMED_STEM_CELL_SPHERES_UP: Genes up-regulated in transformed spheres compared to blebbishields from RT4 cells [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/JINESH_BLEBBISHIELD_TRANSFORMED_STEM_CELL_SPHERES_UP.html]

RIGGI_EWING_SARCOMA_PROGENITOR_UP: Genes up-regulated in mesenchymal stem cells (MSC) engineered to express EWS-FLI1 [GeneID=2130;2321] fusion protein. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/RIGGI_EWING_SARCOMA_PROGENITOR_UP.html]

REACTOME_VISUAL_PHOTOTRANSDUCTION: Visual phototransduction [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_VISUAL_PHOTOTRANSDUCTION.html]

7. Gene Descriptions

NCBI Gene Summary: This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. This member can efficiently reduce aliphatic and aromatic aldehydes, and it is less active on hexoses. It is highly expressed in adrenal gland, small intestine, and colon, and may play an important role in liver carcinogenesis. [provided by RefSeq, Jul 2008]

GeneCards Summary: AKR1B10 (Aldo-Keto Reductase Family 1 Member B10) is a Protein Coding gene. Diseases associated with AKR1B10 include Hepatocellular Carcinoma and Lung Cancer. Among its related pathways are Visual phototransduction and Cyclophosphamide Pathway, Pharmacodynamics. Gene Ontology (GO) annotations related to this gene include aldo-keto reductase (NADP) activity and indanol dehydrogenase activity. An important paralog of this gene is AKR1B15.

UniProtKB/Swiss-Prot Summary: Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols [PMID: 9565553, PMID: 18087047, PMID: 12732097, PMID: 19013440, PMID: 19563777]. Displays strong enzymatic activity toward all-trans-retinal, 9-cis-retinal, and 13-cis-retinal [PMID: 12732097, PMID: 18087047]. Plays a critical role in detoxifying dietary and lipid-derived unsaturated carbonyls, such as crotonaldehyde, 4-hydroxynonenal, trans-2-hexenal, trans-2,4-hexadienal and their glutathione-conjugates carbonyls (GS-carbonyls) [PMID: 19013440, PMID: 19563777]. Displays no reductase activity towards glucose [PMID: 12732097].

8. Cellular Location of Gene Product

Cytoplasmic expression in gastrointestinal tract and gall bladder. Mainly localized to the cytosol. In addition localized to the plasma membrane (based on antibodies targeting proteins from multiple genes). Predicted location: Secreted, Intracellular (different isoforms) [https://www.proteinatlas.org/ENSG00000198074/subcellular]

9. Mechanistic Information

Summary

Akr1b8 encodes an enzyme that functions in the detoxification of reactive aldehydes, such as crotonaldehyde and 4-hydroxynonenal, by their reduction to less reactive alcohols using NADPH [CS: 9]. This activity serves to prevent the accumulation of aldehydes that can cause DNA adducts and initiate lipid peroxidation, events leading to hepatocyte damage and liver disease progression [CS: 8]. Moreover, Akr1b8 is responsible for reducing retinal to retinol, aiding in retinoic acid synthesis crucial for liver cell function and regeneration [CS: 7].

Upon exposure to hepatic insults such as aflatoxin B1, an upsurge in Akr1b8 expression facilitates the enhanced detoxification of resultant carbonyl intermediates, acting as a defense mechanism to ameliorate hepatocellular damage and liver dysfunction [CS: 7]. In liver pathologies like steatohepatitis and non-alcoholic fatty liver disease, where increased levels of aldehydes are generated due to oxidative stress and abnormal lipid metabolism, upregulation of Akr1b8 serves to counteract these harmful substances, suggesting a heightened demand for detoxification to prevent further cellular damage [CS: 8]. Growth factors such as EGF and insulin can stimulate the expression of Akr1b8 through the AP-1 signaling pathway, which supports the liver's capacity for self-repair and regeneration by promoting the detoxification of damaging agents, therefore, facilitating the recovery of liver cells during states of stress and injury [CS: 7].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: esophagus, intestine, stomach (tissue enhanced) [https://www.proteinatlas.org/ENSG00000198074/tissue]

Cell type enchanced: basal keratinocytes, cholangiocytes, distal enterocytes, gastric mucus-secreting cells, proximal enterocytes, suprabasal keratinocytes (cell type enhanced) [https://www.proteinatlas.org/ENSG00000198074/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:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: