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ALDH1A1 (Aldehyde Dehydrogenase 1 family member A1)

Written2019-04Sinem Tunçer, Rümeysa Çamlica, Idris Yilmaz
Vocational School of Health Services, Bilecik Seyh Edebali University, 11230, Bilecik, Turkey Biotechnology Application and Research Center, Bilecik Seyh Edebali University, 11230, Bilecik, Turkey; sinem.tuncer@bilecik.edu.tr (ST); Department of Molecular Biology and Genetics, Bilecik Seyh Edebali University, 11230, Bilecik, Turkey; rumeysacamlca@gmail.com; idris.ylmz2763@gmail.com (RC, IY)

Abstract Aldehyde dehydrogenase 1A1 (ALDH1A1) is a member of the ALDH gene superfamily. Aldehyde dehydrogenases (ALDHs) are responsible for the metabolism of aldehydes (exogenous and endogenous) through NAD(P)+-dependent oxidation to their corresponding carboxylic acids or CoA esters. Different biological functions have been attributed to the different ALDH family members. The cytosolic enzyme ALDH1A1 is involved in the catalysis of retinol (vitamin A) metabolite retinaldehyde to retinoic acid (RA). RA acts as a ligand for the nuclear receptors retinoic receptor (RAR) and the retinoid X receptor (RXR) and therefore regulates the transcriptional activity of genes involved in multiple important processes including proliferation, differentiation, and apoptosis.

Keywords ALDH1A1, retinaldehyde, retinoic acid, retinol, cancer, stem cell, alcohol

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Identity

Alias_namesPUMB1
ALDH1
aldehyde dehydrogenase 1 family
Alias_symbol (synonym)RALDH1
Other aliasALDC
ALDH-E1
ALDH11
HEL-9
HEL-S-53e
HEL12
HGNC (Hugo) ALDH1A1
LocusID (NCBI) 216
Atlas_Id 53077
Location 9q21.13  [Link to chromosome band 9q21]
Location_base_pair Starts at 72900662 and ends at 72953317 bp from pter ( according to hg19-Feb_2009)  [Mapping ALDH1A1.png]
Local_order Starts at 72900662 and ends at 72953317 (according to GRCh38) (Figure 1).
 
  Figure 1. Genomic location of human ALDH1A1 (Chromosome 9 - NC_000009.12, GRCh38.p12 Primary Assembly)
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

DNA/RNA

Note The ALDH gene superfamily is found in Archaea, Eubacteria and Eukarya, indicating a vital role for this family throughout evolutionary history (Jackson et al., 2011). A standardized gene nomenclature system based on divergent evolution and amino acid identity was established for the ALDH superfamily in The Ninth International Symposium on Enzymology and Molecular Biology of Carbonyl Metabolism, in 1998 (Figure 2) (Marchitti et al., 2008). There are 19 known functional aldehyde dehydrogenase (ALDH) genes and many pseudogenes in the human genome (Tomita et al., 2016). ALDH1 family has six members including ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH1L1, and ALDH1L2 (C. K. Yang et al., 2017). Since vertebrate ALDH1A1, ALDH1A2 and ALDH1A3 subunit sequences are highly conserved: subsequent gene duplication events are thought to generate ALDH1A1, ALDH1A2 and ALDH1A3 genes in most vertebrate genomes, except some bony fish (Holmes, 2015). ALDH1A1 homologs are present in most vertebrae species, but are absent in Zebra fish and other fishes in the teleost lineage (Table 1) (Jackson et al., 2011).
Gene SpeciesGene SymbolIdentity (%) DNA
H.sapiensALDH1A1
vs. P.troglodytesALDH1A199,5
vs. M.mulattaALDH1A197,9
vs. C.lupusALDH1A188,4
vs. B.taurusALDH1A190,2
vs. M.musculusAldh1a184,6
vs. R.norvegicusAldh1a183,9
vs. G.gallusALDH1A179,4
vs. X.tropicalisaldh1a174,4
vs. E.gossypiiAGOS_ADR417W54,1
vs. A.thalianaALDH2C457,6
vs. O.sativaOs01g059100056
vs. O.sativaOs01g059130055,5

Table 1. Pairwise alignment of ALDH1A1 gene (in distance from human) (HomoloGene, NCBI).
 
  Figure 2. ALDH Nomenclature
 
  Figure 3. Display of human ALDH1A1 gene transcript exons (Ensembl release 95 - January 2019)
Description The ALDH1A1 gene is a protein coding gene. The gene covers 52656 bp, from 72900662 to 72953317 (NC_000009.12). It is located on the plus strand spanning 13 exons (GRCh38, NCBI Homo sapiens Annotation Release 109).
Transcription This gene has 7 transcripts (splice variants), 161 orthologues and 18 paralogues depending on Ensembl release 95-January 2019 (Table 2). ENST00000297785.7 (ALDH1A1-201) transcript has 13 exons, ENST00000376939.5 (ALDH1A1-202) and ENST00000419959.5 (ALDH1A1-203) transcripts have 8 exons, and ENST00000446946.1 (ALDH1A1-204) transcript has 7 exons (Figure 3).
NameTranscript IDbpCCDSRefSeq
ALDH1A1-201ENST00000297785.72107CCDS6644NM_000689 
ALDH1A1-202ENST00000376939.5822--
ALDH1A1-203ENST00000419959.5806--
ALDH1A1-204ENST00000446946.1805--
ALDH1A1-205ENST00000482210.5879--
ALDH1A1-206ENST00000493113.1604--
ALDH1A1-207ENST00000493311.1209--

Table 2. Transcripts of human ALDH1A1 gene (Ensembl release 95-January 2019)
Studies in human K562 erythroleukemia and Hep3B hepatoma cells showed that the ALDH1A1 promoter contains a positive regulatory region (-91 to +53 bp to the transcription start site) with a CCAAT box as a major cisacting element (Alam et al., 2013). Among CCAAT-recognizing transcription factors, nuclear factor YA ( NFYA) was shown to be involved in ALDH1A1 transcription. Mamat et al. found that in cooperation with POU2F1 (Oct-1), alternatively spliced isoforms of NFYA plays an important role in ALDH1A1 expression in endometrial adenocarcinoma (Mamat et al., 2011). In mouse hepatoma cells, RARA transactivates the Aldh1a1 promoter by binding to the RARE region, located between -91 and -75 bp. Moreover, CEBPB has been demonstrated to transactivate the ALDH1A1 promoter by interacting with the CCAAT box that resides at -75 to -71 bp adjacent to the RARE (Alam et al., 2013).
Pseudogene Not identified.

Protein

Note Aldehyde dehydrogenase 1 family, member A1, also known as ALDH1A1 or retinaldehyde dehydrogenase 1 (RALDH1), is an heterotetramer enzyme that is encoded by the human ALDH1A1 gene. Human ALDH1A1 is 501 amino acids in length (Table 3). ALDH1A1 protein similarity across species are given in Table 4.
NameTranscript IDbpProteinChargeIsoelectric PointMolecular WeightCCDSUniProtRefSeq
ALDH1A1-201ENST00000297785.72107501aa1,06,681154,861.84 g/molCCDS6644P00352 V9HW83NM_000689  NP_000680
ALDH1A1-202ENST00000376939.5822230aa-0,56,242725,314.22 g/mol-Q5SYQ9-
ALDH1A1-203ENST00000419959.5806238aa-1,0 6.106126,097.05 g/mol-Q5SYQ8-
ALDH1A1-204ENST00000446946.1805203aa-1,05,817422,654.11 g/mol-Q5SYQ7-

Table 3. Protein products of human ALDH1A1 gene (Ensembl release 95-January 2019)
Gene SpeciesGene SymbolIdentity (%) Protein
H.sapiensALDH1A1
vs. P.troglodytesALDH1A1100
vs. M.mulattaALDH1A198,8
vs. C.lupusALDH1A189
vs. B.taurusALDH1A191,2
vs. M.musculusAldh1a187
vs. R.norvegicusAldh1a186,4
vs. G.gallusALDH1A184,2
vs. X.tropicalisaldh1a178,2
vs. E.gossypiiAGOS_ADR417W50,7
vs. A.thalianaALDH2C452
vs. O.sativaOs01g059100053,8
vs. O.sativaOs01g059130051,8

Table 4. Pairwise alignment of ALDH1A1 protein sequences (in distance from human) (HomoloGene, NCBI)
Description The human ALDH1 family shares over 60% protein sequence identity and has six subfamily members (C. K. Yang et al., 2017). Crystal structures of mammalian ALDH enzymes have shown that each subunit contains three domains: (1) an NAD(P) + cofactorbinding domain, (2) a catalytic domain, and (3) a bridging domain. A funnel passage leading to the catalytic pocket is found at the interface of these domains. ALDH specificity toward particular aldehyde substrates is thought to be caused by the upper portion of the funnel which is composed of residues from all three domains. The lower portion of the funnel appears to be the catalytic site where hydride transfer from substrate to cofactor occur, is composed of highly conserved residues (Marchitti et al., 2008) (Figure 6).
Expression ALDH1A1 is a highly conserved homotetramer somatic cell plasma protein, expressed in numerous tissues, including liver, kidney, red blood cells, skeletal muscle, lung, breast, lens, stomach, brain, pancreas, testis, prostate, ovary (Jackson et al., 2011; Mamat et al., 2011). The detailed RNA and protein expression information can be found in: Human Protein Atlas (https://www.proteinatlas.org/ENSG00000165092-ALDH1A1/tissue).
Localisation ALDH1A1 is present in the cytosol. Interestingly, Kahlert et al. observed nuclear expression of ALDH1A1 in a small subgroup of patients with colon cancer and rectal cancer, and found that in colon cancer patients, nuclear expression of ALDH1A1 was significantly associated with shortened overall survival (Kahlert et al., 2012).
Function In retinol metabolism (Figure 4), retinol is oxidized by retinol dehydrogenases (RD) to retinal. Later on, retinal is oxidized to retinoic acid (RA) in a reaction catalyzed by the human ALDH isoenzymes ALDH1A1, ALDH1A2, ALDH1A3, and ALDH8A1The metabolized product RA includes all-trans RA (ATRA), 9-cis RA, and 13-cis RA. The ALDH isoforms, especially ALDH1A1, have an affinity for ATRA and 9-cis RA. RA diffuses into the nucleus and acts as a ligand for the retinoic acid receptors (RARA, RARB, RARG) and retinoic X receptors ( RXRA, RXRB, RXRG). Then, the ligand-receptor complex binds to the retinoic acid response element (RARE) in the promoter of target genes and therefore regulates differentiation, apoptosis and/or cell cycle arrest in a context-dependent manner (Marcato et al., 2011b; Tomita et al., 2016). RXRA-/- mice were shown to have decreased liver ALDH1A1 levels, suggesting that RA binding is an activating factor in ALDH1A1 gene expression (Gyamfi, 2006). RA is required for testicular development and ALDH1A1 is absent in genital tissues of humans with androgen receptor-negative testicular feminization. Being an androgen binding protein, ALDH1A1 expression is thought to be regulated also by the androgen receptor (Li et al., 2010; Marchitti et al., 2008).
Aldehyde dehydrogenase (ALDH) enzyme family plays an important role in cellular signal transmission and protection by catalyzing the oxidation of aldehydes (Alam et al., 2013). ALDH1A1 mainly contributes to the biosynthesis of retinoic acid (RA) from vitamin A (Van Der Waals et al., 2018). Inside the cell, Retinol (vitamin A) is oxidized to retinal by retinal dehydrogenases. The retinal is then oxidized to RA in a reaction catalyzed with ALDH1A1, ALDH1A2, ALDH1A3, and ALDH8A1 (Tomita et al., 2016). The RA enters the cell nucleus and binds and activates RA receptors (RARs) or retinoid X receptors (RXRs) to regulate gene expression (Zhao et al., 2014).
ALDH1A1 also plays a role in acetaldehyde metabolism. Acetaldehyde is the first product of ethanol metabolism. Alcohol, taken with alcohol consumption, is converted to acetaldehyde by alcohol dehydrogenase (ADH), catalase and cytochrome P450 2E1. Then, acetaldehyde is metabolized to acetates by ALDH2 and ALDH1A1. Indeed, low ALDH1A1 activity is suggested to be related to alcohol sensitivity in some Caucasian populations ("Identification And Characterisation Of Alcohol-Induced Flushing In Caucasian Subjects", 2017). Moreover, decreased levels of ALDH1A1 were shown in RXRA-/-w/sup> mice, which were more susceptible to alcoholic liver injury (Gyamfi, 2006), while increased ALDH1A1 expression found in brains of alcohol-avoiding DBA/2 mice (Bhave et al., 2006).
ALDH1A1 is predominantly expressed by a subgroup of dopaminergic (DA) neurons in the midbrain (Maring et al., 1985). In DA neurons, ALDH1A1 mediates the oxidation of the cytotoxic dopamine intermediate, 3,4-dihydroxyphenylacetaldehyde (DOPAL), to the less reactive 3,4-dihydroxyphenylacetic acid (DOPAC), and thereby protects the DA neurons from toxicity (Pan et al., 2019). Very recently, ALDH1A1 was reported to mediate the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) (Kim et al., 2015) in DA neurons, where co-release of dopamine and GABA regulates alcohol consumption and preference (Pan et al., 2019). In addition, as a metabolic product of ALDH1A1, RA is known to play a crucial role in neuronal patterning, differentiation, and survival (Pan et al., 2019).
In addition to its role in aldehyde metabolism, ALDH1A1 possesses esterase activity. Collard et al. proposed ALDH1A1 being the major if not the only enzyme responsible for the oxidation of 3-deoxyglucosone to 2-keto-3-deoxygluconate (Collard et al., 2007).
ALDHs are generally categorized as detoxification enzymes. ALDH1A1 was found to offer cellular protection against cytotoxic drugs and implicated in drug-resistance in chemotherapy (Tomita et al., 2016). ALDH1A1 activity has been reported to provide cellular protection against some oxazaphosphorine anticancer drugs, such as cyclophosphamide (CP) and ifosfamide, by detoxifying their major active aldehyde metabolites (Hilton, 1984; Wang et al., 2017).
ALDH1A1 also plays a vital role as a marker of stem cells and cancer stem cells. Experimental data indicate that ALDH1 activity, predominantly attributed to isotype ALDH1A1, is tissue and cancer type specific. On the other hand, although elevated ALDH1 activity and ALDH1A1 overexpression are associated with poor cancer prognosis, high ALDH1 and ALDH1A1 levels are not always correlated with highly malignant phenotypes and poor clinical outcome in a range of cancers (Tomita et al., 2016). It is suggested that ALDH1A1 can be a useful marker for cancer stem cells derived from tumors that normally do not express high levels of ALDH1A1, including breast, lung, esophagus, colon, and stomach (Tomita et al., 2016; Xing et al., 2014).
ALDH1A1 also plays a key role in the cellular defense against oxidative stress: ALDH activity is required to maintain sufficiently low Reactive Oxygen Species (ROS) level. Human ALDH1A1 was shown to efficiently oxidize lipid peroxidation-derived aldehydes, like 4-Hydroxynonenal (4-HNE), hexanal, and Malondialdehyde (MDA) (MANZER et al., 2003), and Aldh1a1 knock-out mouse models demonstrated that ALDH1A1 plays a crucial role in protecting the mouse eye lens and cornea by detoxifying lipid peroxidation-derived aldehydes and preventing cataract formation induced by oxidative stresses (Mice et al., 2008).
In addition to its catalytic functions, ALDH1A1 has also non-catalytic roles. Similar with other ALDHs, ALDH1A1 acts as corneal and lens crystallins in mammalian eye tissue and contributes to the transparent and refractive properties of the eye (Vasiliou et al., 2013), as well as protects the eye from tissue damage as mentioned earlier. Finally, since ALDH1A1 can bind thyroid hormone and its expression is induced by estrogens, it is suggested that the enzyme may be regulated by or involved in hormone signaling (Marchitti et al., 2008).
 
  Figure 4. Retinoic acid signaling pathway: Retinoic acid (RA), generated by ALDHs, can function in the paracrine or endocrine manner by diffusing into neighbouring cells or the nucleus. In the nucleus, RA binds to heterodimers of the retinoic acid receptor (RAR) and retinoid x receptor (RXR). Activated receptor complexes induce transcription of target genes by binding to retinoic acid response elements (RAREs).
 
  Figure 5. ALDH1A1 regulation and function: Once inside the cytoplasm, retinol is oxidized to retinal, then retinal is oxidized to RA by several isoforms of ALDH. RA binds to dimers of RARA and RXRs to induce the expression of its downstream target genes. RA can bind to dimers of RXRs and ESR1 (ERα) as well as induce the expression of MYC and CCND1 (cyclin D1) in ERα-expressing cells. In addition to RA binding to the RAR, CEBPB and OCT1 binding to the ALDH1A1 promoter enhances the ALDH1A1 transcription. NFYA was also shown to activate ALDH1A1 transcription while DDB2 was shown to suppress ALDH1A1 expression by preventing CEBPB binding to the promoter. The details can be found in the text. The figure is modified from Tomita et al. (Tomita et al., 2016)).
 
  Figure 6. Structure of human ALDH1A1: Structure of human ALDH1A1 determined using X-ray diffraction (PDB ID: 4WJ9) (Morgan and Hurley, 2015; Rose et al., 2018).

Mutations

Note A list of ALDH1A1 mutations in cancer can be found in: COSMIC, the Catalogue of Somatic Mutations in Cancer, https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=ALDH1A1
Consequences of indicated ALDH1A1 mutations are necessary to evaluate.

Implicated in

Note ALDH1A1 encodes the enzyme ALDH1A1 (also known as retinaldehyde dehydrogenase 1-RALDH1) which is involved in several metabolic processes and therefore implicated in various diseases and conditions.
  
Entity Parkinson's disease
Note Deficiency in ALDH activity, specifically in ALDH1A1 activity in the substantia nigra, is suggested to lead accumulation of neurotoxic aldehydes and subsequent cell death seen in Parkinson's disease, and possibly in other neurodegenerative disorders. ALDH1 mRNA expression was reported to be decreased in surviving neurons of Parkinson's disease patients (Basso et al., 2004). Wey et al. showed that deletion of two isoforms of aldehyde dehydrogenase, Aldh1a1 and Aldh2, which are known to be involved in dopamine metabolism in the brain, resulted in elevated levels of the neurotoxic aldehydes DOPAL and 4-HNE and loss of dopaminergic neurons in the substantia nigra, and caused a Parkinsonian phenotype characterized by age-dependent deficits in motor performance (Wey et al., 2012).
  
  
Entity Obesity
Note Adipogenesis is a process regulated by retinoids. Being an ALDH1A1 substrate, retinaldehyde was shown to down-regulate the expression of adipogenesis genes in vitro. In vivo, retinaldehyde decreased fat levels and increased insulin sensitivity in an obese mouse model. Therefore, both in vivo and in vitro results suggest that retinaldehyde may act as an adipogenesis inhibiting signaling metabolite (Ziouzenkova et al., 2007).
As an ALDH1A1 metabolite, RA has also an effect on adipogenesis. RA treatment of obese mice resulted in weight loss and increased insulin sensitivity in addition to increased expression of RAR and other genes (Berry and Noy, 2009). In comparison with other vitamin A metabolizing enzymes responsible in the production of RA, the major enzyme expressed during adipogenesis is ALDH1A1, and ALDH1A1 deficiency was shown to result in impaired adipogenesis (Harrison et al., 2011). Retinal, the substrate of ALDH1A1, is suggested to inhibit PPARG (peroxisome proliferator-activated receptor-gamma) a transcription factor known as the master regulator of adipogenesis. Ziouzenkova et al. showed that retinal is present in rodent fat, binds retinol-binding proteins (CRBP1, RBP4), inhibits adipogenesis and suppresses PPARG and RXR responses. In vivo, mice lacking the Aldh1a1 resisted diet-induced obesity and insulin resistance and showed increased energy dissipation. In ob/ob mice, administrating retinal or an Aldh1a1 inhibitor reduced fat and increased insulin sensitivity (Ziouzenkova et al., 2007).
  
  
Entity Alcohol-related phenotypes
Note Because of its involvement in ethanol metabolism, ALDH1A1 is a candidate for alcohol research. ALDH1A1 has been implicated in several alcohol-related phenotypes, including alcoholism, alcohol-induced flushing, and alcohol sensitivity. Studies suggest that low ALDH1A1 activity may contribute to alcohol sensitivity and alcohol-induced flushing reaction in Caucasians and some Asians. Polymorphisms located on both coding and promoter regions of ALDH1A1 were found to influence alcoholic predisposition (Spence et al., 2003).
Kim et al. showed that an evolutionarily conserved GABA synthesis pathway involves Aldh1a1. They found that repeated ethanol exposure reduces GABA co-release from the ventral tegmental area (VTA) dopamine neurons and downregulation of Aldh1a through gene targeting or RNA interference increases alcohol consumption in mice. These findings highlight the importance of Aldh1a1 and VTA GABA co-release in moderating alcohol consumption (Kim et al., 2015).
  
  
Entity Cancer
Note ALDH1A1 has been shown to be related to the stemness of both cancer stem cells and normal tissue stem cells. Recent reports reveal that ALDH1 and specifically ALDH1A1 is a useful cancer stem cell marker that can be used to enrich tumor-initiating subpopulations from various cell lines and primary tumors (Tomita et al., 2016).
  
  
Entity Breast cancer
Note ALDH1A1 is a breast cancer biomarker for prediction of tumor progression and its expression is correlated with poor survival (Liu et al., 2014). High ALDH activity and CD44 expression (ALDHhiCD44+) were found to contribute to metastatic behavior and therapy resistance to breast cancer (Croker et al., 2017).
  
  
Entity Colorectal cancer
Note ALDH1A1 protein expression was found to be increased significantly in colorectal cancer (CRC) tissues compared with matched non-tumor adjacent tissues using immunohistochemistry (IHC). Therefore, the protein is suggested to be a potential prognostic marker in patients with CRC. Moreover, in patients with CRC, increased expression of the ALDH1A1 protein was shown to be associated with the lymph node metastasis (W. et al., 2018). ALDH1A1 expression was found to be associated also with features of poor prognosis, including a poorly differentiated histology and "right-sidedness" of the primary tumor, and with shorter overall survival (Van Der Waals et al., 2018).
  
  
Entity Esophageal cancer (squamous cell carcinoma)
Note Depending on Yang et al., ALDH1A1 (high) cancer stem-like cells contribute to the invasion, metastasis and poor outcome of human esophageal squamous cell carcinoma. ALDH1A1 high esophageal squamous cell carcinoma cells were found to have increased levels of mRNA for VIM (vimentin), matrix metalloproteinase 2, 7, and 9 ( MMP2, MMP7 and MMP9), but decreased the level of CDH1 (E-cadherin) mRNA, suggesting that epithelial-mesenchymal transition and MMPs may be associated with the high invasive and metastatic capabilities of ALDH1A1 high cells (L. Yang et al., 2014).
  
  
Entity Gastric cancer
Note The positive rate of ALDH1A1 expression was shown to be 60% in gastric cancer patients (L. Yang et al., 2017), but there was no significant difference between survival rates of ALDH1A1-positive and ALDH1A1-negative patients (Li et al., 2016; L. Yang et al., 2017).
  
  
Entity Liver cancer
Note Tanaka et al. found there was no significant difference in the ALDH1A1-mRNA level between tumorous and non-tumorous tissues of hepatocellular carcinoma patients. In addition, there was no correlation between tumorous ALDH1A1-mRNA level and the clinic-pathological features. They found that in human hepatocellular carcinoma, ALDH1A1-overexpressing cells are differentiated cells rather than cancer stem or progenitor cells (Tanaka et al., 2015).
  
  
Entity Lung cancer
Note The expression of LGR5 and ALDH1A1 were found to be closely associated with the tumorigenicity, metastasis and poor prognosis of non-small cell lung cancer, and LGR5 + cells in non-small cell lung cancer are proposed to be the cancer cells with stem cell-like properties due to the significant correlation between LGR5 and ALDH1A1 (Gao et al., 2015).
  
  
Entity Multiple myeloma
Note Yang et al. reported that increased expression of ALDH1 in multiple myeloma (MM) is a marker of tumor-initiating cells (TICs) that is further associated with chromosomal instability (CIN). They found, between the ALDH1 members, ALDH1A1 is most abundantly expressed member in myeloma and enforced expression of ALDH1A1 in myeloma cells results in increased clonogenicity, tumor formation in mice, and resistance to myeloma drugs in vitro and in vivo (Y. Yang et al., 2014). 
  
  
Entity Ovarian cancer
Note Landen Jr et al. showed that in ovarian cancer, ALDH1A1-positive population has properties of cancer stem cells, and this population is associated with taxane and platinum resistance. Additionally, this population was found to be resensitized to chemotherapy both in vitro and in vivo by down-regulation of ALDH1A1 expression (Landen et al., 2010).
More recently, Cui et al. showed that in ovarian cancer, DNA damage-binding protein 2 (DDB2) suppresses non-cancer stem cell to cancer stem cell conversion by repressing ALDH1A1 transcription. Mechanistically, DDB2 binds to the ALDH1A1 gene promoter, enhances the enrichment of histone H3K27me3, and thereby competes with the transcription factor CEBPB for binding to this region, and eventually inhibits the promoter activity of the ALDH1A1 gene (Cui et al., 2018) (Figure 5).
  
  
Entity Pancreatic cancer
Note ALDH1A1 is a pancreatic stem cell marker and is highly enriched in a subpopulation of cells which are extremely resistant to chemotherapy. Furthermore, ALDH1 is highly enriched in surgical specimens from patients with pancreatic cancer who had undergone preoperative chemo-radiation therapy compared to untreated patients (Mizukami et al., 2014).
  
  
Entity Papillary thyroid carcinoma
Note ALDH1A1 levels were significantly higher in papillary thyroid carcinoma samples than normal thyroid samples and ALDH1A1 overexpression was significantly associated with extrathyroid extension, pT status, pN status and TNM stage. The Kaplan-Meier survival analysis shows that high ALDH1A1 expression reflects a poorer lymph node recurrence-free survival (LN-RFS) and distant recurrence-free survival (DRFS) in papillary thyroid carcinoma patients, as compared with patients who have low ALDH1A1 expression. Multivariate analysis confirmed ALDH1A1 expression as an independent prognostic factor for LN-RFS and DRFS in papillary thyroid carcinoma patients (Xing et al., 2014).
  
  
Entity Prostate cancer
Note ALDH1A1 is a cancer stem cell marker in prostate cancer (Kalantari et al., 2017). Cojoc et al. found that the expression of ALDH1A1 is regulated by the WNT signaling pathway. Inhibition of the WNT pathway led to a decrease in ALDH(+) tumor progenitor population and to radiosensitization of cancer cells (Cojoc et al., 2015).
  

To be noted

Aldefluor assay is widely used to detect ALDH activity by flow cytometry. This assay is based on the conversion of the ALDH substrate BODIPY- aminoacetaldehyde (BAAA) to the fluorescence product BODIPY-aminoacetate. Therefore, the level of fluorescence corresponds to the amount of ALDH activity present in the cell. N,N-diethylamino-benzaldehyde (DEAB), an inhibitor of ALDH activity, is supplied as a negative control for the assay. When the assay has been developed, DEAB was found to be a potent inhibitor of cytosolic ALDH (ALDH1) but not mitochondrial ALDH (ALDH2). Because of this, the Aldefluor Assay was thought to measure cellular ALDH1A1 activity. However, recent studies have shown that DEAB inhibits other ALDH isoenzymes and as a result, the Aldefluor assay will detect stem cells with high levels of other ALDH isoenzyme activity, including ALDH1A2, ALDH1A3, and ALDH2 (Marcato et al., 2011a; Moreb et al., 2012). Morgan et al. analyzed the mechanism underlying DEAB dependent inhibition and found that DEAB is a substrate for ALDH3A1, ALDH1A1, ALDH1A3, ALDH1B1, ALDH5A1, but the turnover rates are so slow that it acts as an inhibitor for more rapidly metabolized aldehyde substrates. Additionally, they did not found appreciable turnover of DEAB with either ALDH1A2 or ALDH2, where DEAB behaves as a covalent inhibitor for both isoenzymes (Morgan et al., 2015).
In IHC analyses, ALDH1A1 can be specifically identified with isotype-specific antibodies. However, when it is the stem cell population, Aldefluor assay has to be used to identify ALDH1A1 activity (Tomita et al., 2016). Because of the broad and varied nature of the interaction between DEAB and ALDH isoenzymes, the results of Aldefluor assay should be interpreted with caution with regard to which particular ALDH isoenzymes contribute to the observed fluorescence in the flow cytometry assay. Together with Aldefluor assay, other specific measurement methods are needed to determine ALDH1A1 expression and activity in the biological samples. In this sense, the generation of selective inhibitor(s) for ALDH1A1 appears to be particularly important.
Targeting ALDH may be a potential strategy for cancer treatment. Since Aldh1a1<>-/- mice are viable, this means that ALDH1A1 inhibition may not damage normal tissue stem cells. Therefore, ALDH1A1 targeted therapy has a potential for the elimination of cancer stem cells.

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Differential Functional Roles of ALDH1A1 and ALDH1A3 in Mediating Metastatic Behavior and Therapy Resistance of Human Breast Cancer Cells
Croker AK, Rodriguez-Torres M, Xia Y, Pardhan S, Leong HS, Lewis JD, Allan AL
Int J Mol Sci 2017 Sep 22;18(10)
PMID 28937653
 
DDB2 represses ovarian cancer cell dedifferentiation by suppressing ALDH1A1
Cui T, Srivastava AK, Han C, Wu D, Wani N, Liu L, Gao Z, Qu M, Zou N, Zhang X, Yi P, Yu J, Bell EH, Yang SM, Maloney DJ, Zheng Y, Wani AA, Wang QE
Cell Death Dis 2018 May 1;9(5):561
PMID 29752431
 
The role of LGR5 and ALDH1A1 in non-small cell lung cancer: Cancer progression and prognosis
Gao F, Zhou B, Xu JC, Gao X, Li SX, Zhu GC, Zhang XG, Yang C
Biochem Biophys Res Commun 2015 Jun 26;462(2):91-8
PMID 25881507
 
The role of retinoid X receptor alpha in regulating alcohol metabolism
Gyamfi MA, Kocsis MG, He L, Dai G, Mendy AJ, Wan YJ
J Pharmacol Exp Ther 2006 Oct;319(1):360-8
PMID 16829625
 
Role of aldehyde dehydrogenase in cyclophosphamide-resistant L1210 leukemia
Hilton J
Cancer Res 1984 Nov;44(11):5156-60
PMID 6488175
 
Comparative and evolutionary studies of vertebrate ALDH1A-like genes and proteins
Holmes RS
Chem Biol Interact 2015 Jun 5;234:4-11
PMID 25446856
 
Update on the aldehyde dehydrogenase gene (ALDH) superfamily
Jackson B, Brocker C, Thompson DC, Black W, Vasiliou K, Nebert DW, Vasiliou V
Hum Genomics 2011 May;5(4):283-303
PMID 21712190
 
Expression analysis of aldehyde dehydrogenase 1A1 (ALDH1A1) in colon and rectal cancer in association with prognosis and response to chemotherapy
Kahlert C, Gaitzsch E, Steinert G, Mogler C, Herpel E, Hoffmeister M, Jansen L, Benner A, Brenner H, Chang-Claude J, Rahbari N, Schmidt T, Klupp F, Grabe N, Lahrmann B, Koch M, Halama N, Büchler M, Weitz J
Ann Surg Oncol 2012 Dec;19(13):4193-201
PMID 22878609
 
Increased Expression of ALDH1A1 in Prostate Cancer is Correlated With Tumor Aggressiveness: A Tissue Microarray Study of Iranian Patients
Kalantari E, Saadi FH, Asgari M, Shariftabrizi A, Roudi R, Madjd Z
Appl Immunohistochem Mol Morphol 2017 Sep;25(8):592-598
PMID 26894647
 
Aldehyde dehydrogenase 1a1 mediates a GABA synthesis pathway in midbrain dopaminergic neurons
Kim JI, Ganesan S, Luo SX, Wu YW, Park E, Huang EJ, Chen L, Ding JB
Science 2015 Oct 2;350(6256):102-6
PMID 26430123
 
Targeting aldehyde dehydrogenase cancer stem cells in ovarian cancer
Landen CN Jr, Goodman B, Katre AA, Steg AD, Nick AM, Stone RL, Miller LD, Mejia PV, Jennings NB, Gershenson DM, Bast RC Jr, Coleman RL, Lopez-Berestein G, Sood AK
Mol Cancer Ther 2010 Dec;9(12):3186-99
PMID 20889728
 
Multiple and additive functions of ALDH3A1 and ALDH1A1: cataract phenotype and ocular oxidative damage in Aldh3a1(-/-)/Aldh1a1(-/-) knock-out mice
Lassen N, Bateman JB, Estey T, Kuszak JR, Nees DW, Piatigorsky J, Duester G, Day BJ, Huang J, Hines LM, Vasiliou V
J Biol Chem 2007 Aug 31;282(35):25668-76
PMID 17567582
 
The prognostic roles of ALDH1 isoenzymes in gastric cancer
Li K, Guo X, Wang Z, Li X, Bu Y, Bai X, Zheng L, Huang Y
Onco Targets Ther 2016 Jun 7;9:3405-14
PMID 27354812
 
ALDH1A1 is a marker for malignant prostate stem cells and predictor of prostate cancer patients' outcome
Li T, Su Y, Mei Y, Leng Q, Leng B, Liu Z, Stass SA, Jiang F
Lab Invest 2010 Feb;90(2):234-44
PMID 20010854
 
ALDH1A1 expression correlates with clinicopathologic features and poor prognosis of breast cancer patients: a systematic review and meta-analysis
Liu Y, Lv DL, Duan JJ, Xu SL, Zhang JF, Yang XJ, Zhang X, Cui YH, Bian XW, Yu SC
BMC Cancer 2014 Jun 17;14:444
PMID 24938375
 
Transcriptional Regulation of Aldehyde Dehydrogenase 1A1 Gene by Alternative Spliced Forms of Nuclear Factor Y in Tumorigenic Population of Endometrial Adenocarcinoma
Mamat S, Ikeda J, Tian T, Wang Y, Luo W, Aozasa K, Morii E
Genes Cancer 2011 Oct;2(10):979-84
PMID 22701763
 
Aldehyde dehydrogenase: its role as a cancer stem cell marker comes down to the specific isoform
Marcato P, Dean CA, Giacomantonio CA, Lee PW
Cell Cycle 2011 May 1;10(9):1378-84
PMID 21552008
 
Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily
Marchitti SA, Brocker C, Stagos D, Vasiliou V
Expert Opin Drug Metab Toxicol 2008 Jun;4(6):697-720
PMID 18611112
 
Partial purification and properties of human brain aldehyde dehydrogenases
Maring JA, Deitrich RA, Little R
J Neurochem 1985 Dec;45(6):1903-10
 
Immunohistochemical analysis of cancer stem cell markers in pancreatic adenocarcinoma patients after neoadjuvant chemoradiotherapy
Mizukami T, Kamachi H, Mitsuhashi T, Tsuruga Y, Hatanaka Y, Kamiyama T, Matsuno Y, Taketomi A
BMC Cancer 2014 Sep 21;14:687
PMID 25240521
 
The enzymatic activity of human aldehyde dehydrogenases 1A2 and 2 (ALDH1A2 and ALDH2) is detected by Aldefluor, inhibited by diethylaminobenzaldehyde and has significant effects on cell proliferation and drug resistance
Moreb JS, Ucar D, Han S, Amory JK, Goldstein AS, Ostmark B, Chang LJ
Chem Biol Interact 2012 Jan 5;195(1):52-60
PMID 22079344
 
Development of a high-throughput in vitro assay to identify selective inhibitors for human ALDH1A1
Morgan CA, Hurley TD
Chem Biol Interact 2015 Jun 5;234:29-37
PMID 25450233
 
N,N-diethylaminobenzaldehyde (DEAB) as a substrate and mechanism-based inhibitor for human ALDH isoenzymes
Morgan CA, Parajuli B, Buchman CD, Dria K, Hurley TD
Chem Biol Interact 2015 Jun 5;234:18-28
PMID 25512087
 
ALDH1A1 regulates postsynaptic μ-opioid receptor expression in dorsal striatal projection neurons and mitigates dyskinesia through transsynaptic retinoic acid signaling
Pan J, Yu J, Sun L, Xie C, Chang L, Wu J, Hawes S, Saez-Atienzar S, Zheng W, Kung J, Ding J, Le W, Chen S, Cai H
Sci Rep 2019 Mar 5;9(1):3602
PMID 30837649
 
Human aldehyde dehydrogenase 3A1 (ALDH3A1): biochemical characterization and immunohistochemical localization in the cornea
Pappa A, Estey T, Manzer R, Brown D, Vasiliou V
Biochem J 2003 Dec 15;376(Pt 3):615-23
PMID 12943535
 
Concerted action of aldehyde dehydrogenases influences depot-specific fat formation
Reichert B, Yasmeen R, Jeyakumar SM, Yang F, Thomou T, Alder H, Duester G, Maiseyeu A, Mihai G, Harrison EH, Rajagopalan S, Kirkland JL, Ziouzenkova O
Mol Endocrinol 2011 May;25(5):799-809
PMID 21436255
 
NGL viewer: web-based molecular graphics for large complexes
Rose AS, Bradley AR, Valasatava Y, Duarte JM, Prlic A, Rose PW
Bioinformatics 2018 Nov 1;34(21):3755-3758
PMID 29850778
 
Evaluation of aldehyde dehydrogenase 1 promoter polymorphisms identified in human populations
Spence JP, Liang T, Eriksson CJ, Taylor RE, Wall TL, Ehlers CL, Carr LG
Alcohol Clin Exp Res 2003 Sep;27(9):1389-94
PMID 14506398
 
ALDH1A1-overexpressing cells are differentiated cells but not cancer stem or progenitor cells in human hepatocellular carcinoma
Tanaka K, Tomita H, Hisamatsu K, Nakashima T, Hatano Y, Sasaki Y, Osada S, Tanaka T, Miyazaki T, Yoshida K, Hara A
Oncotarget 2015 Sep 22;6(28):24722-32
PMID 26160842
 
Aldehyde dehydrogenase 1A1 in stem cells and cancer
Tomita H, Tanaka K, Tanaka T, Hara A
Oncotarget 2016 Mar 8;7(10):11018-32
PMID 26783961
 
Aldehyde dehydrogenases: from eye crystallins to metabolic disease and cancer stem cells
Vasiliou V, Thompson DC, Smith C, Fujita M, Chen Y
Chem Biol Interact 2013 Feb 25;202(1-3):2-10
PMID 23159885
 
Aldehyde dehydrogenase 1A1 increases NADH levels and promotes tumor growth via glutathione/dihydrolipoic acid-dependent NAD(+) reduction
Wang B, Chen X, Wang Z, Xiong W, Xu T, Zhao X, Cao Y, Guo Y, Li L, Chen S, Huang S, Wang X, Fang M, Shen Z
Oncotarget 2017 May 8;8(40):67043-67055
PMID 28978015
 
Identification and characterisation of alcohol-induced flushing in Caucasian subjects
Ward RJ, McPherson AJ, Chow C, Ealing J, Sherman DI, Yoshida A, Peters TJ
Alcohol Alcohol 1994 Jul;29(4):433-8
PMID 7986281
 
Neurodegeneration and motor dysfunction in mice lacking cytosolic and mitochondrial aldehyde dehydrogenases: implications for Parkinson's disease
Wey MC, Fernandez E, Martinez PA, Sullivan P, Goldstein DS, Strong R
PLoS One 2012;7(2):e31522
PMID 22384032
 
High ALDH1A1 expression correlates with poor survival in papillary thyroid carcinoma
Xing Y, Luo DY, Long MY, Zeng SL, Li HH
World J Surg Oncol 2014 Feb 3;12:29
PMID 24485040
 
Aldehyde dehydrogenase 1 (ALDH1) isoform expression and potential clinical implications in hepatocellular carcinoma
Yang CK, Wang XK, Liao XW, Han CY, Yu TD, Qin W, Zhu GZ, Su H, Yu L, Liu XG, Lu SC, Chen ZW, Liu Z, Huang KT, Liu ZT, Liang Y, Huang JL, Xiao KY, Peng MH, Winkle CA, O'Brien SJ, Peng T
PLoS One 2017 Aug 8;12(8):e0182208
PMID 28792511
 
ALDH1A1 defines invasive cancer stem-like cells and predicts poor prognosis in patients with esophageal squamous cell carcinoma
Yang L, Ren Y, Yu X, Qian F, Bian BS, Xiao HL, Wang WG, Xu SL, Yang J, Cui W, Liu Q, Wang Z, Guo W, Xiong G, Yang K, Qian C, Zhang X, Zhang P, Cui YH, Bian XW
Mod Pathol 2014 May;27(5):775-83
 
Predictive Value of Stemness Factor Sox2 in Gastric Cancer Is Associated with Tumor Location and Stage
Yang L, Xu JF, Kang Q, Li AQ, Jin P, Wang X, He YQ, Li N, Cheng T, Sheng JQ
PLoS One 2017 Jan 3;12(1):e0169124
PMID 28046028
 
Expression of Aldehyde Dehydrogenase 1A1 (ALDH1A1) as a Prognostic Biomarker in Colorectal Cancer Using Immunohistochemistry
Yang W, Wang Y, Wang W, Chen Z, Bai G
Med Sci Monit 2018 May 7 [revised 2018 Jan 1];24:2864-2872
PMID 29748529
 
NEK2 mediates ALDH1A1-dependent drug resistance in multiple myeloma
Yang Y, Zhou W, Xia J, Gu Z, Wendlandt E, Zhan X, Janz S, Tricot G, Zhan F
Oncotarget 2014 Dec 15;5(23):11986-97
PMID 25230277
 
NOTCH-induced aldehyde dehydrogenase 1A1 deacetylation promotes breast cancer stem cells
Zhao D, Mo Y, Li MT, Zou SW, Cheng ZL, Sun YP, Xiong Y, Guan KL, Lei QY
J Clin Invest 2014 Dec;124(12):5453-65
PMID 25384215
 
Retinaldehyde represses adipogenesis and diet-induced obesity
Ziouzenkova O, Orasanu G, Sharlach M, Akiyama TE, Berger JP, Viereck J, Hamilton JA, Tang G, Dolnikowski GG, Vogel S, Duester G, Plutzky J
Nat Med 2007 Jun;13(6):695-702
PMID 17529981
 
ALDH1A1 expression is associated with poor differentiation, 'right-sidedness' and poor survival in human colorectal cancer
van der Waals LM, Borel Rinkes IHM, Kranenburg O
PLoS One 2018 Oct 11;13(10):e0205536
PMID 30308036
 

Citation

This paper should be referenced as such :
Tunçer S, Çamlca R, Yilmaz I.
ALDH1A1 (Aldehyde Dehydrogenase 1 family member A1);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/ALDH1A1ID53077ch9q21.html


External links

Nomenclature
HGNC (Hugo)ALDH1A1   402
Cards
AtlasALDH1A1ID53077ch9q21
Entrez_Gene (NCBI)ALDH1A1  216  aldehyde dehydrogenase 1 family member A1
AliasesALDC; ALDH-E1; ALDH1; ALDH11; 
HEL-9; HEL-S-53e; HEL12; PUMB1; RALDH1
GeneCards (Weizmann)ALDH1A1
Ensembl hg19 (Hinxton)ENSG00000165092 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000165092 [Gene_View]  ENSG00000165092 [Sequence]  chr9:72900662-72953317 [Contig_View]  ALDH1A1 [Vega]
ICGC DataPortalENSG00000165092
TCGA cBioPortalALDH1A1
AceView (NCBI)ALDH1A1
Genatlas (Paris)ALDH1A1
WikiGenes216
SOURCE (Princeton)ALDH1A1
Genetics Home Reference (NIH)ALDH1A1
Genomic and cartography
GoldenPath hg38 (UCSC)ALDH1A1  -     chr9:72900662-72953317 -  9q21.13   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)ALDH1A1  -     9q21.13   [Description]    (hg19-Feb_2009)
GoldenPathALDH1A1 - 9q21.13 [CytoView hg19]  ALDH1A1 - 9q21.13 [CytoView hg38]
ImmunoBaseENSG00000165092
Mapping of homologs : NCBIALDH1A1 [Mapview hg19]  ALDH1A1 [Mapview hg38]
OMIM100640   
Gene and transcription
Genbank (Entrez)AB209821 AF003341 AI074764 AK000118 AK026641
RefSeq transcript (Entrez)NM_000689
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)ALDH1A1
Cluster EST : UnigeneHs.76392 [ NCBI ]
CGAP (NCI)Hs.76392
Alternative Splicing GalleryENSG00000165092
Gene ExpressionALDH1A1 [ NCBI-GEO ]   ALDH1A1 [ EBI - ARRAY_EXPRESS ]   ALDH1A1 [ SEEK ]   ALDH1A1 [ MEM ]
Gene Expression Viewer (FireBrowse)ALDH1A1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)216
GTEX Portal (Tissue expression)ALDH1A1
Human Protein AtlasENSG00000165092-ALDH1A1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP00352   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP00352  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP00352
Splice isoforms : SwissVarP00352
PhosPhoSitePlusP00352
Domaine pattern : Prosite (Expaxy)ALDEHYDE_DEHYDR_CYS (PS00070)    ALDEHYDE_DEHYDR_GLU (PS00687)   
Domains : Interpro (EBI)Ald_DH/histidinol_DH    Ald_DH_C    Ald_DH_CS_CYS    Ald_DH_CS_GLU    Ald_DH_N    Aldehyde_DH_dom   
Domain families : Pfam (Sanger)Aldedh (PF00171)   
Domain families : Pfam (NCBI)pfam00171   
Conserved Domain (NCBI)ALDH1A1
DMDM Disease mutations216
Blocks (Seattle)ALDH1A1
PDB (RSDB)4WB9    4WJ9    4WP7    4WPN    4X4L    5AC2    5L2M    5L2N    5L2O    5TEI   
PDB Europe4WB9    4WJ9    4WP7    4WPN    4X4L    5AC2    5L2M    5L2N    5L2O    5TEI   
PDB (PDBSum)4WB9    4WJ9    4WP7    4WPN    4X4L    5AC2    5L2M    5L2N    5L2O    5TEI   
PDB (IMB)4WB9    4WJ9    4WP7    4WPN    4X4L    5AC2    5L2M    5L2N    5L2O    5TEI   
Structural Biology KnowledgeBase4WB9    4WJ9    4WP7    4WPN    4X4L    5AC2    5L2M    5L2N    5L2O    5TEI   
SCOP (Structural Classification of Proteins)4WB9    4WJ9    4WP7    4WPN    4X4L    5AC2    5L2M    5L2N    5L2O    5TEI   
CATH (Classification of proteins structures)4WB9    4WJ9    4WP7    4WPN    4X4L    5AC2    5L2M    5L2N    5L2O    5TEI   
SuperfamilyP00352
Human Protein Atlas [tissue]ENSG00000165092-ALDH1A1 [tissue]
Peptide AtlasP00352
HPRD00001
IPIIPI00218914   IPI00910463   IPI00642144   IPI00644077   IPI00644628   
Protein Interaction databases
DIP (DOE-UCLA)P00352
IntAct (EBI)P00352
FunCoupENSG00000165092
BioGRIDALDH1A1
STRING (EMBL)ALDH1A1
ZODIACALDH1A1
Ontologies - Pathways
QuickGOP00352
Ontology : AmiGOretinoid metabolic process  retinal dehydrogenase activity  retinal dehydrogenase activity  aldehyde dehydrogenase (NAD) activity  aldehyde dehydrogenase (NAD) activity  aldehyde dehydrogenase (NAD) activity  GTPase activator activity  androgen binding  cytoplasm  cytosol  cytosol  cytosol  ethanol oxidation  cellular aldehyde metabolic process  benzaldehyde dehydrogenase (NAD+) activity  retinol metabolic process  positive regulation of GTPase activity  NAD binding  oxidation-reduction process  fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate  extracellular exosome  negative regulation of cold-induced thermogenesis  
Ontology : EGO-EBIretinoid metabolic process  retinal dehydrogenase activity  retinal dehydrogenase activity  aldehyde dehydrogenase (NAD) activity  aldehyde dehydrogenase (NAD) activity  aldehyde dehydrogenase (NAD) activity  GTPase activator activity  androgen binding  cytoplasm  cytosol  cytosol  cytosol  ethanol oxidation  cellular aldehyde metabolic process  benzaldehyde dehydrogenase (NAD+) activity  retinol metabolic process  positive regulation of GTPase activity  NAD binding  oxidation-reduction process  fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate  extracellular exosome  negative regulation of cold-induced thermogenesis  
Pathways : KEGGRetinol metabolism   
NDEx NetworkALDH1A1
Atlas of Cancer Signalling NetworkALDH1A1
Wikipedia pathwaysALDH1A1
Orthology - Evolution
OrthoDB216
GeneTree (enSembl)ENSG00000165092
Phylogenetic Trees/Animal Genes : TreeFamALDH1A1
HOGENOMP00352
Homologs : HomoloGeneALDH1A1
Homology/Alignments : Family Browser (UCSC)ALDH1A1
Gene fusions - Rearrangements
Fusion : FusionGDB10251    1458    1459    1460    1461    1462    16870   
Fusion : Fusion_HubALDH1A1--ALDH1A1    ALDH1A1--ANXA1    ALDH1A1--CHD2    ALDH1A1--CREBZF    ALDH1A1--ELL    ALDH1A1--EPB41L4A    ALDH1A1--FXYD1    ALDH1A1--PRUNE2    ALDH1A1--SSBP2    ALDH1A1--TG    ALDH1A1--TYK2    ALDH1A1--UPF3A    ALDH1A1--YBX1    ASB3--ALDH1A1    HSPA8--ALDH1A1   
NMRK1--ALDH1A1    RHOBTB3--ALDH1A1    STRBP--ALDH1A1    ZFP1--ALDH1A1   
Fusion : QuiverALDH1A1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerALDH1A1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ALDH1A1
dbVarALDH1A1
ClinVarALDH1A1
1000_GenomesALDH1A1 
Exome Variant ServerALDH1A1
ExAC (Exome Aggregation Consortium)ENSG00000165092
GNOMAD BrowserENSG00000165092
Varsome BrowserALDH1A1
Genetic variants : HAPMAP216
Genomic Variants (DGV)ALDH1A1 [DGVbeta]
DECIPHERALDH1A1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisALDH1A1 
Mutations
ICGC Data PortalALDH1A1 
TCGA Data PortalALDH1A1 
Broad Tumor PortalALDH1A1
OASIS PortalALDH1A1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICALDH1A1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDALDH1A1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch ALDH1A1
DgiDB (Drug Gene Interaction Database)ALDH1A1
DoCM (Curated mutations)ALDH1A1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ALDH1A1 (select a term)
intoGenALDH1A1
NCG5 (London)ALDH1A1
Cancer3DALDH1A1(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM100640   
Orphanet
DisGeNETALDH1A1
MedgenALDH1A1
Genetic Testing Registry ALDH1A1
NextProtP00352 [Medical]
TSGene216
GENETestsALDH1A1
Target ValidationALDH1A1
Huge Navigator ALDH1A1 [HugePedia]
snp3D : Map Gene to Disease216
BioCentury BCIQALDH1A1
ClinGenALDH1A1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD216
Chemical/Pharm GKB GenePA24692
Clinical trialALDH1A1
Miscellaneous
canSAR (ICR)ALDH1A1 (select the gene name)
DataMed IndexALDH1A1
Probes
Litterature
PubMed295 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineALDH1A1
EVEXALDH1A1
GoPubMedALDH1A1
iHOPALDH1A1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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