Details for: AKR7A3

Gene ID: 22977

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: AKR7A3

Ensembl ID: ENSG00000162482

Description: aldo-keto reductase family 7 member A3

Cell Significance Landscape

Associated with

Significant Cells

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

  • midzonal region hepatocyte CL0019028
    CSI 8.63
    rCSI 20.25%
    PRS 87.94
  • foveolar cell of stomach CL0002179
    CSI 8.06
    rCSI 17.17%
    PRS 92.18
  • colonocyte CL1000347
    CSI 7.28
    rCSI 10.44%
    PRS 88.38
  • colon epithelial cell CL0011108
    CSI 7.04
    rCSI 7.37%
    PRS 87.88
  • enterocyte CL0000584
    CSI 6.01
    rCSI 9.69%
    PRS 87.16
  • intestine goblet cell CL0019031
    CSI 5.63
    rCSI 5%
    PRS 87.67
  • goblet cell CL0000160
    CSI 5.05
    rCSI 4.77%
    PRS 87.94
  • BEST4+ enteroycte CL4030026
    CSI 5.02
    rCSI 6.24%
    PRS 89.98
  • mucous neck cell CL0000651
    CSI 4.85
    rCSI 7%
    PRS 92.69
  • astrocyte of the cerebral cortex CL0002605
    CSI 4.69
    rCSI 10.51%
    PRS 77.51
  • enteroendocrine cell CL0000164
    CSI 4.68
    rCSI 6.4%
    PRS 88.67
  • intrahepatic cholangiocyte CL0002538
    CSI 4.63
    rCSI 11.11%
    PRS 90.39
  • pancreatic acinar cell CL0002064
    CSI 4.63
    rCSI 6.16%
    PRS 92.98
  • parietal cell CL0000162
    CSI 3.92
    rCSI 33.72%
    PRS 94.52
  • epithelial cell of proximal tubule CL0002306
    CSI 3.58
    rCSI 8.75%
    PRS 83.53
  • periportal region hepatocyte CL0019026
    CSI 3.5
    rCSI 13.6%
    PRS 87.25
  • paneth cell of epithelium of small intestine CL1000343
    CSI 3.46
    rCSI 9.7%
    PRS 93.22
  • basal cell of epidermis CL0002187
    CSI 3.39
    rCSI 6.01%
    PRS 61.27
  • transit amplifying cell of colon CL0009011
    CSI 3.18
    rCSI 3.73%
    PRS 90.18
  • transit amplifying cell of small intestine CL0009012
    CSI 3.17
    rCSI 13.9%
    PRS 93.41
  • enteroendocrine cell of small intestine CL0009006
    CSI 2.92
    rCSI 6.42%
    PRS 92.95
  • peptic cell CL0000155
    CSI 2.8
    rCSI 27.51%
    PRS 94.19
  • centrilobular region hepatocyte CL0019029
    CSI 2.54
    rCSI 6.63%
    PRS 86.23
  • M cell of gut CL0000682
    CSI 2.53
    rCSI 2.69%
    PRS 92.17
  • enterocyte of epithelium of small intestine CL1000334
    CSI 2.34
    rCSI 36.15%
    PRS 92.79
  • hepatocyte CL0000182
    CSI 1.81
    rCSI 3.24%
    PRS 88.83
  • transit amplifying cell CL0009010
    CSI 1.66
    rCSI 2.53%
    PRS 93.51
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.65
    rCSI 4.45%
    PRS 92.27
  • epithelial cell of proximal tubule segment 3 CL4030011
    CSI 1.54
    rCSI 12.26%
    PRS 85.81
  • colon goblet cell CL0009039
    CSI 1.5
    rCSI 3.58%
    PRS 91.88
  • type L enteroendocrine cell CL0002279
    CSI 1.21
    rCSI 2.27%
    PRS 92.03
  • enteroendocrine cell of colon CL0009042
    CSI 0.82
    rCSI 3.82%
    PRS 92.22
  • type EC enteroendocrine cell CL0000577
    CSI 0.67
    rCSI 2.38%
    PRS 91.34
  • paneth cell of colon CL0009009
    CSI 0.31
    rCSI 3.05%
    PRS 93.35

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)

Loading network (please wait)...

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 [AKR7A3](/details-gene/22977) (aldo-keto reductase family 7 member A3) is a protein-coding gene located on chromosome 1p36.13. It encodes a member of the aldo-keto reductase superfamily, enzymes that play a crucial role in the metabolism of aldehydes and ketones. Functionally, [AKR7A3](/details-gene/22977) is best characterized for its role in detoxification, particularly of aflatoxin B1, a potent dietary carcinogen ([Link](https://doi.org/10.1093/carcin/20.7.1215)). Its expression is highly significant in metabolically active and secretory epithelial tissues. **Overall**, it is a key marker for [midzonal region hepatocytes](/details-cell/CL0019028) and various cell types throughout the gastrointestinal tract, including [foveolar cells of the stomach](/details-cell/CL0002179) and [colonocytes](/details-cell/CL1000347), consistent with a primary role in xenobiotic metabolism at key environmental interfaces. ## Cellular Roles and Expression Landscape The expression profile of [AKR7A3](/details-gene/22977) underscores its specialized function in metabolic and detoxification processes, primarily within epithelial cells of the digestive system and liver. **Overall**, the gene shows the highest significance in cells responsible for detoxification and secretion. It is a top marker for [midzonal region hepatocytes](/details-cell/CL0019028) (CSI: 8.63), the primary site of xenobiotic metabolism in the liver. Its prominence extends throughout the gastrointestinal tract, with very high significance in [foveolar cells of the stomach](/details-cell/CL0002179) (CSI: 8.06), [colonocytes](/details-cell/CL1000347) (CSI: 7.28), [enterocytes](/details-cell/CL0000584) (CSI: 6.01), and [goblet cells](/details-cell/CL0000160) (CSI: 5.05). This pattern suggests a critical role in defending the body against ingested toxins and metabolizing endogenous aldehydes along the entire digestive tract. The gene's activity is also notable in other secretory and metabolic tissues, including [pancreatic acinar cells](/details-cell/CL0002064) and [epithelial cells of the proximal tubule](/details-cell/CL0002306) in the kidney. Interestingly, [AKR7A3](/details-gene/22977) also shows significant expression in [astrocytes of the cerebral cortex](/details-cell/CL0002605), suggesting a potential, though less characterized, role in metabolic processes or detoxification within the central nervous system. The collective expression pattern points to [AKR7A3](/details-gene/22977) being a key enzymatic workhorse in tissues that form a barrier to the external environment or are central hubs of metabolism. ## Pathways and Molecular Function The functional annotations for [AKR7A3](/details-gene/22977) align precisely with its observed cellular expression pattern. Its primary molecular function is defined as `aldo-keto reductase (nadph) activity` ([GO:0004033](https://www.ebi.ac.uk/QuickGO/term/GO:0004033)), participating in the `cellular aldehyde metabolic process` ([GO:0006081](https://www.ebi.ac.uk/QuickGO/term/GO:0006081)). These activities are central to the Reactome pathway `Biological oxidations` ([R-HSA-211859](https://reactome.org/content/detail/R-HSA-211859)). Most specifically, [AKR7A3](/details-gene/22977) is a component of the `Aflatoxin activation and detoxification` pathway ([R-HSA-5423646](https://reactome.org/content/detail/R-HSA-5423646)). This function is critical for protecting cells from the mutagenic effects of aflatoxin B1 dialdehyde, a process that is highly relevant in [hepatocytes](/details-cell/CL0019028) ([Link](https://doi.org/10.1021/tx7004458)). According to GO annotations, the protein is localized mainly to the `cytoplasm` ([GO:0005737](https://www.ebi.ac.uk/QuickGO/term/GO:0005737)) and `cytosol` ([GO:0005829](https://www.ebi.ac.uk/QuickGO/term/GO:0005829)), which is consistent with its role in metabolizing soluble cytosolic substrates. ## Research Directions Given that [AKR7A3](/details-gene/22977) is located in a chromosomal region frequently altered in human tumors ([Link](https://doi.org/10.1038/sj.onc.1206684)), its role in carcinogenesis, particularly as a protective agent, warrants further investigation. Its high specificity for detoxification pathways in epithelial tissues positions it as a key factor in chemical carcinogenesis. ### Proposed Hypotheses 1. **Hypothesis 1:** Reduced expression or polymorphic variants of [AKR7A3](/details-gene/22977) in [colonocytes](/details-cell/CL1000347) may increase susceptibility to colorectal cancer by impairing the detoxification of dietary pro-carcinogens, leading to higher rates of DNA adduct formation and somatic mutations. 2. **Hypothesis 2:** In the central nervous system, [AKR7A3](/details-gene/22977) expression in [astrocytes](/details-cell/CL0002605) serves a neuroprotective function by metabolizing reactive aldehydes generated during oxidative stress, and its downregulation could contribute to the pathology of neurodegenerative diseases associated with lipid peroxidation. ### Experimental Approach To test Hypothesis 1, one could utilize a combination of in vitro and clinical sample analysis. An effective experimental design would be to use CRISPR-Cas9 to knock out [AKR7A3](/details-gene/22977) in a human colon epithelial cell line (e.g., NCM460) or organoid model. These knockout and wild-type models would then be exposed to dietary carcinogens, such as heterocyclic amines found in cooked meat. The impact could be assessed by measuring levels of DNA adducts using mass spectrometry, quantifying DNA damage via comet assays, and monitoring long-term cell survival and transformation potential. ### Therapeutic Potential [AKR7A3](/details-gene/22977) is unlikely to be a target for inhibition, as its function is primarily protective. Instead, it presents a potential target for **activation** or chemoprevention strategies. For individuals with low-activity variants or those at high risk of exposure to carcinogens metabolized by this enzyme, pharmacological agents that upregulate [AKR7A3](/details-gene/22977) expression or enhance its activity could offer a protective benefit. It could also serve as a valuable biomarker for stratifying individuals' risk for developing certain cancers of the liver or gastrointestinal tract based on their genetic or expression status.

Genular Protein ID: 3710659674

Symbol: ARK73_HUMAN

Name: Aflatoxin B1 aldehyde reductase member 3

UniProtKB Accession Codes:

O95154 Q86SR4 Q8IVN6 Q8N5V6 Q8TAX1 Q9NUC3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 6 DNASU 1 DisGeNET 1 EC 1 EMBL 6 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 8 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 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 SABIO-RK 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: 10383892

Title: cDNA cloning, expression and activity of a second human aflatoxin B1-metabolizing member of the aldo-keto reductase superfamily, AKR7A3.

PubMed ID: 10383892

DOI: 10.1093/carcin/20.7.1215

PubMed ID: 12879023

Title: Aflatoxin B1 aldehyde reductase (AFAR) genes cluster at 1p35-1p36.1 in a region frequently altered in human tumour cells.

PubMed ID: 12879023

DOI: 10.1038/sj.onc.1206684

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 18416522

Title: Protection against aflatoxin B1-induced cytotoxicity by expression of the cloned aflatoxin B1-aldehyde reductases rat AKR7A1 and human AKR7A3.

PubMed ID: 18416522

DOI: 10.1021/tx7004458

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

Sequence Information:

  • Length: 331
  • Mass: 37206
  • Checksum: B9C32C33C7102AB3
  • Sequence:
    • MSRQLSRARP ATVLGAMEMG RRMDAPTSAA VTRAFLERGH TEIDTAFVYS EGQSETILGG 
LGLRLGGSDC RVKIDTKAIP LFGNSLKPDS LRFQLETSLK RLQCPRVDLF YLHMPDHSTP 
VEETLRACHQ LHQEGKFVEL GLSNYAAWEV AEICTLCKSN GWILPTVYQG MYNAITRQVE 
TELFPCLRHF GLRFYAFNPL AGGLLTGKYK YEDKNGKQPV GRFFGNTWAE MYRNRYWKEH 
HFEGIALVEK ALQAAYGASA PSMTSATLRW MYHHSQLQGA HGDAVILGMS SLEQLEQNLA 
AAEEGPLEPA VVDAFNQAWH LVTHECPNYF R