1. Gene Aliases

ALDH1A1, Aldehyde Dehydrogenase 1 Family Member A1, RALDH1, ALDH1, PUMB1, 3-Deoxyglucosone Dehydrogenase, Retinaldehyde Dehydrogenase 1, Aldehyde Dehydrogenase 1A1, Retinal Dehydrogenase 1, EC 1.2.1.36, ALDH-E1, RALDH 1, ALHDII, ALDC, Epididymis Secretory Sperm Binding Protein Li 53e, Aldehyde Dehydrogenase 1 Family, Member A1, Aldehyde Dehydrogenase Family 1 Member A1, Aldehyde Dehydrogenase, Liver Cytosolic, Aldehyde Dehydrogenase 1, Soluble, Aldehyde Dehydrogenase, Cytosolic, Epididymis Luminal Protein 12, Acetaldehyde Dehydrogenase 1, Epididymis Luminal Protein 9, ALDH Class 1, EC 1.2.1.19, EC 1.2.1.28, EC 1.2.1.3, HEL-S-53e, EC 1.2.1, ALDH11, RalDH1, HEL-9, HEL12

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=ALDH1A1&keywords=Aldh1a1].

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:

9-cis-retinoic acid biosynthetic process [The chemical reactions and pathways resulting in the formation of 9-cis-retinoic acid, a metabolically active vitamin A derivative. GO:0042904]

9-cis-retinoic acid metabolic process [The chemical reactions and pathways involving 9-cis-retinoic acid, a metabolically active vitamin A derivative. GO:0042905]

apoptotic process [A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. GO:0006915]

cellular detoxification of aldehyde [Any process carried out at the cellular level that reduces or removes the toxicity of an aldehyde. These may include transport of aldehydes away from sensitive areas and to compartments or complexes whose purpose is sequestration of the toxic substance. GO:0110095]

embryonic eye morphogenesis [The process occurring in the embryo by which the anatomical structures of the post-embryonic eye are generated and organized. GO:0048048]

estrous cycle [A type of ovulation cycle, which occurs in most mammalian therian females, where the endometrium is resorbed if pregnancy does not occur. GO:0044849]

fructosamine catabolic process [The chemical reactions and pathways resulting in the breakdown of fructosamine, a fructose molecule containing an amino group in place of a hydroxyl group. GO:0030392]

fructose catabolic process [The chemical reactions and pathways resulting in the breakdown of fructose, the ketohexose arabino-2-hexulose. GO:0006001]

gamma-aminobutyric acid biosynthetic process [The chemical reactions and pathways resulting in the formation of gamma-aminobutyric acid (GABA, 4-aminobutyrate), an amino acid which acts as a neurotransmitter in some organisms.|See also the biological process term 'neurotransmitter biosynthetic process ; GO:0042136'. GO:0009449]

kidney development [The process whose specific outcome is the progression of the kidney over time, from its formation to the mature structure. The kidney is an organ that filters the blood and/or excretes the end products of body metabolism in the form of urine. GO:0001822]

liver development [The process whose specific outcome is the progression of the liver over time, from its formation to the mature structure. The liver is an exocrine gland which secretes bile and functions in metabolism of protein and carbohydrate and fat, synthesizes substances involved in the clotting of the blood, synthesizes vitamin A, detoxifies poisonous substances, stores glycogen, and breaks down worn-out erythrocytes. GO:0001889]

maintenance of lens transparency [A homeostatic process in which the lens is maintained in a highly refractive, transparent state to allow for optimal focusing of light on the retina. GO:0036438]

midgut development [The process whose specific outcome is the progression of the midgut over time, from its formation to the mature structure. The midgut is the middle part of the alimentary canal from the stomach, or entrance of the bile duct, to, or including, the large intestine. GO:0007494]

negative regulation of cold-induced thermogenesis [Any process that stops, prevents, or reduces the rate of cold-induced thermogenesis. GO:0120163]

optic cup morphogenesis involved in camera-type eye development [The invagination of the optic vesicle to form two-walled indentations, the optic cups, that will go on to form the retina. This process begins with the optic vesicle becoming a two-walled structure and its subsequent shape changes. It does not include the fate commitment of cells to become the pigmented retina and the neural retina. An example of this process is found in Mus musculus. GO:0002072]

positive regulation of apoptotic process [Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process.|This term should only be used when it is not possible to determine which phase or subtype of the apoptotic process is positively regulated by a gene product. Whenever detailed information is available, the more granular children terms should be used. GO:0043065]

response to estradiol [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 stimulus by estradiol, a C18 steroid hormone hydroxylated at C3 and C17 that acts as a potent estrogen. GO:0032355]

response to ethanol [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 an ethanol stimulus. GO:0045471]

response to organic cyclic compound [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 an organic cyclic compound stimulus. GO:0014070]

response to oxidative stress [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 oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals. GO:0006979]

response to retinoic acid [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 retinoic acid stimulus. GO:0032526]

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]

retinoic acid biosynthetic process [The chemical reactions and pathways resulting in the biosynthesis of retinoic acid, one of the three components that makes up vitamin A. GO:0002138]

retinoic acid metabolic process [The chemical reactions and pathways involving retinoic acid, one of the three components that makes up vitamin A. GO:0042573]

retinoid metabolic process [The chemical reactions and pathways involving retinoids, any member of a class of isoprenoids that contain or are derived from four prenyl groups linked head-to-tail. Retinoids include retinol and retinal and structurally similar natural derivatives or synthetic compounds, but need not have vitamin A activity. GO:0001523]

retinol metabolic process [The chemical reactions and pathways involving retinol, one of the three compounds that makes up vitamin A. GO:0042572]

MSigDB Signatures:

KEGG_RETINOL_METABOLISM: Retinol metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_RETINOL_METABOLISM.html]

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

REACTOME_ETHANOL_OXIDATION: Ethanol oxidation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_ETHANOL_OXIDATION.html]

REACTOME_METABOLISM_OF_CARBOHYDRATES: Metabolism of carbohydrates [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_METABOLISM_OF_CARBOHYDRATES.html]

WP_DISORDERS_OF_FRUCTOSE_METABOLISM: Disorders of fructose metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_DISORDERS_OF_FRUCTOSE_METABOLISM.html]

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

WP_FATTY_ACID_OMEGA_OXIDATION: Fatty acid omega oxidation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_FATTY_ACID_OMEGA_OXIDATION.html]

WP_FOLATE_ALCOHOL_AND_CANCER_PATHWAY_HYPOTHESES: Folate alcohol and cancer pathway hypotheses [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_FOLATE_ALCOHOL_AND_CANCER_PATHWAY_HYPOTHESES.html]

REACTOME_BIOLOGICAL_OXIDATIONS: Biological oxidations [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_BIOLOGICAL_OXIDATIONS.html]

WP_VITAMIN_A_AND_CAROTENOID_METABOLISM: Vitamin A and carotenoid metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_VITAMIN_A_AND_CAROTENOID_METABOLISM.html]

WP_ETHANOL_EFFECTS_ON_HISTONE_MODIFICATIONS: Ethanol effects on histone modifications [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_ETHANOL_EFFECTS_ON_HISTONE_MODIFICATIONS.html]

REACTOME_RA_BIOSYNTHESIS_PATHWAY: RA biosynthesis pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_RA_BIOSYNTHESIS_PATHWAY.html]

REACTOME_FRUCTOSE_CATABOLISM: Fructose catabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_FRUCTOSE_CATABOLISM.html]

REACTOME_SIGNALING_BY_NUCLEAR_RECEPTORS: Signaling by Nuclear Receptors [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SIGNALING_BY_NUCLEAR_RECEPTORS.html]

REACTOME_SIGNALING_BY_RETINOIC_ACID: Signaling by Retinoic Acid [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SIGNALING_BY_RETINOIC_ACID.html]

REACTOME_PHASE_I_FUNCTIONALIZATION_OF_COMPOUNDS: Phase I - Functionalization of compounds [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_PHASE_I_FUNCTIONALIZATION_OF_COMPOUNDS.html]

7. Gene Descriptions

NCBI Gene Summary: The protein encoded by this gene belongs to the aldehyde dehydrogenase family. Aldehyde dehydrogenase is the next enzyme after alcohol dehydrogenase in the major pathway of alcohol metabolism. There are two major aldehyde dehydrogenase isozymes in the liver, cytosolic and mitochondrial, which are encoded by distinct genes, and can be distinguished by their electrophoretic mobility, kinetic properties, and subcellular localization. This gene encodes the cytosolic isozyme. Studies in mice show that through its role in retinol metabolism, this gene may also be involved in the regulation of the metabolic responses to high-fat diet.

GeneCards Summary: ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1) is a Protein Coding gene. Diseases associated with ALDH1A1 include Alcohol Dependence and Androgen Insensitivity Syndrome. Among its related pathways are Oxidation by cytochrome P450 and Fructose metabolism. Gene Ontology (GO) annotations related to this gene include oxidoreductase activity and acyl-CoA dehydrogenase activity. An important paralog of this gene is ALDH1A2.

UniProtKB/Swiss-Prot Summary: Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid [PMID: 19296407, PMID: 12941160, PMID: 15623782, PMID: 17175089, PMID: 26373694, PMID: 25450233]. Functions downstream of retinol dehydrogenases and catalyzes the oxidation of retinaldehyde into retinoic acid, the second step in the oxidation of retinol/vitamin A into retinoic acid. This pathway is crucial to control the levels of retinol and retinoic acid, two important molecules which excess can be teratogenic and cytotoxic. Also oxidizes aldehydes resulting from lipid peroxidation like (E)-4-hydroxynon-2-enal/HNE, malonaldehyde and hexanal that form protein adducts and are highly cytotoxic. By participating for instance to the clearance of (E)-4-hydroxynon-2-enal/HNE in the lens epithelium prevents the formation of HNE-protein adducts and lens opacification [PMID: 19296407, PMID: 12941160, PMID: 15623782]. Functions also downstream of fructosamine-3-kinase in the fructosamine degradation pathway by catalyzing the oxidation of 3-deoxyglucosone, the carbohydrate product of fructosamine 3-phosphate decomposition, which is itself a potent glycating agent that may react with lysine and arginine side-chains of proteins [PMID: 17175089]. Has also an aminobutyraldehyde dehydrogenase activity and is probably part of an alternative pathway for the biosynthesis of GABA/4-aminobutanoate in midbrain, thereby playing a role in GABAergic synaptic transmission.

8. Cellular Location of Gene Product

Cytoplasmic expression in selected tissues. Localized to the cytosol. Predicted location: Intracellular [https://www.proteinatlas.org/ENSG00000165092/subcellular]

9. Mechanistic Information

Summary

Aldh1a1, as a cytosolic aldehyde dehydrogenase, plays a crucial role in detoxifying aldehydes produced during lipid peroxidation, a process often exacerbated in liver diseases and toxicities [CS: 8]. In conditions like nonalcoholic fatty liver disease (NAFLD), where lipid accumulation and subsequent peroxidation are prominent, Aldh1a1 expression is upregulated as a protective response [CS: 7]. This upregulation aids in reducing the accumulation of cytotoxic aldehydes like (E)-4-hydroxynon-2-enal/HNE, malonaldehyde, and hexanal, which can form harmful protein adducts [CS: 8]. By catalyzing the oxidation of these aldehydes to less harmful carboxylic acids, Aldh1a1 mitigates cellular damage and prevents further disease progression [CS: 9].

In the context of liver toxicity, such as that induced by alpha-naphthyl isothiocyanate (ANIT), the decreased expression of Aldh1a1 contributes to the exacerbation of toxic effects due to reduced detoxification capacity [CS: 7]. Normally, Aldh1a1 would oxidize toxic aldehydes to carboxylic acids, thus neutralizing their harmful effects [CS: 9]. However, in the reduced presence of Aldh1a1, there's an accumulation of these aldehydes, leading to increased cellular damage and toxicity [CS: 7]. This mechanism also explains the observed upregulation of Aldh1a1 in conditions of acute inflammation, as seen in lipopolysaccharide-treated rats, where its increased expression in periportal macrophages might be an adaptive response to counteract the elevated production of cytotoxic aldehydes during inflammatory processes [CS: 6].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: liver (tissue enhanced) [https://www.proteinatlas.org/ENSG00000165092/tissue]

Cell type enchanced: hepatocytes, leydig cells (cell type enhanced) [https://www.proteinatlas.org/ENSG00000165092/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

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