ALDH1A1

Summary

ALDH1A1 (aldehyde dehydrogenase 1 family member A1, HGNC:402) is a protein-coding gene on chromosome 9q21.13, encoding Aldehyde dehydrogenase 1A1 (P00352). Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid.

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.

Source: NCBI Gene 216 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 57 total — 1 pathogenic
• Druggable target: yes — 468 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000689

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:402
Approved symbol	ALDH1A1
Name	aldehyde dehydrogenase 1 family member A1
Location	9q21.13
Locus type	gene with protein product
Status	Approved
Aliases	RALDH1
Ensembl gene	ENSG00000165092
Ensembl biotype	protein_coding
Entrez	216

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 21 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000297785, ENST00000376939, ENST00000419959, ENST00000446946, ENST00000482210, ENST00000493113, ENST00000493311, ENST00000856200, ENST00000856201, ENST00000856202, ENST00000856203, ENST00000856204, ENST00000856205, ENST00000856206, ENST00000856207, ENST00000856208, ENST00000856209, ENST00000856210, ENST00000856211, ENST00000856212, ENST00000856213, ENST00000966554, ENST00000966555, ENST00000966556

RefSeq mRNA: 1 — MANE Select: NM_000689 NM_000689

CCDS: CCDS6644

Canonical transcript exons

ENST00000297785 — 13 exons

Exon	Start	End
ENSE00001090236	72918720	72918822
ENSE00001090238	72909602	72909759
ENSE00001090239	72916920	72917104
ENSE00001090241	72924019	72924132
ENSE00001090244	72905958	72906032
ENSE00001090246	72911958	72912122
ENSE00001709544	72900671	72901280
ENSE00001876240	72952935	72953053
ENSE00003480541	72930879	72931019
ENSE00003491402	72928892	72929021
ENSE00003493396	72940148	72940252
ENSE00003559685	72927116	72927177
ENSE00003602265	72925484	72925612

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 99.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 66.8859 / max 12137.3800, expressed in 990 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100982	58.6676	957
100981	6.0105	592
100995	1.7376	96
100984	0.1169	16
100979	0.0840	37
100994	0.0808	37
100993	0.0714	39
100992	0.0536	27
100985	0.0491	21
100983	0.0145	5

Top tissues by expression

300 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.84	gold quality
nasal cavity epithelium	UBERON:0005384	99.76	gold quality
epithelium of bronchus	UBERON:0002031	99.71	gold quality
bronchus	UBERON:0002185	99.69	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.68	gold quality
islet of Langerhans	UBERON:0000006	99.62	gold quality
jejunal mucosa	UBERON:0000399	99.60	gold quality
nasal cavity mucosa	UBERON:0001826	99.59	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.59	gold quality
duodenum	UBERON:0002114	99.58	gold quality
corpus epididymis	UBERON:0004359	99.54	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.22	gold quality
body of pancreas	UBERON:0001150	99.19	gold quality
cardia of stomach	UBERON:0001162	99.08	gold quality
caput epididymis	UBERON:0004358	98.99	gold quality
seminal vesicle	UBERON:0000998	98.96	gold quality
right lobe of liver	UBERON:0001114	98.91	gold quality
gall bladder	UBERON:0002110	98.87	gold quality
liver	UBERON:0002107	98.82	gold quality
pancreas	UBERON:0001264	98.81	gold quality
substantia nigra pars compacta	UBERON:0001965	98.81	gold quality
body of stomach	UBERON:0001161	98.66	gold quality
trachea	UBERON:0003126	98.65	gold quality
right lung	UBERON:0002167	98.60	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.60	gold quality
stomach	UBERON:0000945	98.46	gold quality
tibial nerve	UBERON:0001323	98.35	gold quality
pylorus	UBERON:0001166	98.29	gold quality
left ovary	UBERON:0002119	98.29	gold quality
small intestine	UBERON:0002108	98.28	gold quality

Single-cell (SCXA)

Detected in 34 experiment(s), a significant marker in 32.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	4692.84
E-GEOD-83139	yes	4149.43
E-CURD-46	yes	3790.19
E-ENAD-27	yes	3253.72
E-HCAD-31	yes	2931.19
E-MTAB-10283	yes	2418.77
E-MTAB-8495	yes	2311.12
E-MTAB-9906	yes	1134.06
E-GEOD-124472	yes	917.17
E-HCAD-10	yes	639.20
E-MTAB-3929	yes	258.47
E-MTAB-10432	yes	232.02
E-CURD-6	yes	200.45
E-HCAD-4	yes	142.89
E-MTAB-6701	yes	127.69

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CTNNB1, EZH2, PITX3, RARA, RXRA, RXRB, TLX1

miRNA regulators (miRDB)

36 targeting ALDH1A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-590-5P	99.25	70.76	930
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-6830-3P	98.62	68.07	1760

Literature-anchored findings (GeneRIF, showing 40)

• Effect of gene on proliferation arrest in a non-small cell bronchopulmonary cancer line (PMID:12174908)
• The promoter region of a gene can influence gene expression, the ALDH1A1 promoter regions were studied to identify polymorphism, to assess their functional significance, and to determine whether they were associated with a risk for developing alcoholism. (PMID:14506398)
• ALDH1 is strongly and specifically expressed in human mesencephalic dopamine neurons. Low levels of ALDH1 expression correlate with dopamine neuron dysfunction in the two investigated human conditions. (PMID:14678778)
• ALDH1A1*2 may be associated with protection from the development of alcohol and other substance use disorders. (PMID:15597079)
• Results demonstrate that aldehyde dehydrogenase is a key regulator of hematopoietic stem cell differentiation. (PMID:16857736)
• Random mutagenesis followed by a filter-based screening assay has been used to identify a mutant of human class 1 aldehyde dehydrogenase (ALDH1) that was no longer inhibited by Mg(2+) ions but was activated in their presence. (PMID:16878979)
• ALDH1A1 appears to be the major if not the only enzyme responsible for the oxidation of 3-deoxyglucosone to 2-keto-3-deoxygluconate. (PMID:17175089)
• ALDH1 can be a dermal biomarker for atopic dermatitis disease. (PMID:17222227)
• promoter polymorphism ALDH1A1*2 may be associated with increased risk for the development of alcohol dependence in Indo-Trinidadians (PMID:17286337)
• Retinoic-acid-induced RAR-CAK signaling events appear to proceed intrinsically during granulocytic development of normal primitive hematopoietic cells. ALDH-governed RA availability may mediate this process by initiating RAR-CAK signaling. (PMID:17628022)
• Overexpression of ALDH1A1 inhibits lymphopoiesis and promotes myelopoiesis in murine hematopoietic progenitors to alter cell fate and induce tumor growth (PMID:18082256)
• findings show differential expression of aldehyde dehydrogenase 1 between fibroids & myometrium is maintained in cell culture (without endothelial cells), & that this gene is differentially regulated by retinoids in myometrial compared with fibroid cells (PMID:18343808)
• ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. (PMID:18371393)
• analysis of bioactivation of nitroglycerin by purified mitochondrial and cytosolic aldehyde dehydrogenases ALDH1 and ALDH2 (PMID:18450747)
• ALDH, expressed along CD133, can more specifically characterize the tumorigenic liver cancer stem cells population. (PMID:18644979)
• Down-regulation of aldehyde dehydrogenase 1A1 by siRNA transfection reveals its involvement in promoting and inhibiting pancreatic cancer cell lines. (PMID:18848913)
• In summary, we have identified a molecular signature that distinguishes NF1-PA from S-PA and found that ALDH1L1 underexpression is associated with aggressive histology and/or biologic behavior (PMID:19018242)
• specific down regulation of ALDH1A1 and ALDH3A1 in Lenti 1+3 cells and in comparison to 12 other ALDH genes detected (PMID:19025616)
• This study provides further evidence for a role for ALDH1A1 in alcohol consumption behaviour, including problem drinking and possibly alcohol dependence, in Finnish population. (PMID:19129088)
• lens ALDH1A1(acetaldehyde dehydrogenase 1) is an important defense enzyme against oxidative stress, protecting the eye lens from oxidative damage leading to cataracts (PMID:19296407)
• ALDH1 was a favorable prognostic factor in ovarian carcinoma (PMID:19329942)
• Breast cancers with ALDH1+ cancer stem cells posses biologically aggressive phenotypes that tend to have a poor prognosis. (PMID:19385968)
• ALDH1L1 had higher mean expression levels across regions in all psychiatric groups relative to normal control. (PMID:19447584)
• it is likely that ALDH1 is a specific marker for the cancer stem-like cells of head and neck squamous cell carcinoma. (PMID:19450560)
• Gene duplication event that gave rise to Aldh1a1 and Aldh1a2 was more recent than the duplication event that gave rise to Aldh1a3. (PMID:19478994)
• novel ALDH1A1 allele, ALDH1A1*4 , was identified in an Indo-Trinidadian alcoholic with an A inserted at position -554 relative to the translational start site, +1 (PMID:19706361)
• results indicate that targeting up-regulation of 4-hydroxynonenal-detoxifying enzymes like ALDH1A1, possibly by gene therapy, may be a therapeutic strategy for protecting neurons against oxidative damage in neurodegenerative diseases. (PMID:19774675)
• Increased expression of aldehyde dehydrogenase is associated with colon cancer. (PMID:19808966)
• high degree of stromal expression of ALDH1 was significantly associated with best disease-free survival as well as a trend for overall survival in breast cancer (PMID:19911270)
• ALDH1A1 (aldehyde dehydrogenase 1 family member A1) is a marker for malignant prostate stem cells and predictor of prostate cancer patients’ outcome (PMID:20010854)
• ata demonstrate that the overexpression of Twist in breast cells can promote the generation of a cancer stem cell phenotype characterized by the high expression of CD44, little or no expression of CD24, and increased aldehyde dehydrogenase 1 activity. (PMID:20019840)
• ALDH1A1 may serve as a useful marker for monitoring the progression of bladder tumo (PMID:20142235)
• ALDH1, CD44, and cytokeratin have roles in breast cancer progression (PMID:20228222)
• a novel cancer stem cell marker, ALDH1 can be used for tumors whose corresponding normal tissues express ALDH1 in relatively restricted or limited levels such as breast, lung, ovarian or colon cancer (PMID:20422001)
• High aldehyde dehydrogenase activity is associated with tumor-initiating and metastasis-initiating cells in prostate cancer (PMID:20516116)
• The benign stroma of BRCA1 mutation carriers shows higher ALDH1 expression than age-matched controls, implying that BRCA1 may be an (in)direct regulator of mammary stromal ALDH1 expression. (PMID:20585849)
• Sphere-forming cells with elevated ALDH1 are a possible candidate for sarcoma stem cells, possessing strong chemo-resistant capacities. (PMID:20596639)
• Prognostic impact of this and other cancer stem cell markers expression in colorectal cancer. (PMID:20606680)
• The ALDH1A1 subpopulation is associated with chemoresistance and outcome in ovarian cancer patients, and targeting ALDH1A1 sensitizes resistant cells to chemotherapy. (PMID:20889728)
• aldehyde dehydrogenase 1 has a role in the antitumor effect of the Src inhibitor dasatinib (PMID:20959018)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Aldh1a7	ENSMUSG00000024747
mus_musculus	Aldh1a1	ENSMUSG00000053279
rattus_norvegicus	Aldh1a1	ENSRNOG00000017619
rattus_norvegicus	Aldh1a7	ENSRNOG00000017878
drosophila_melanogaster	CG8665	FBGN0032945
drosophila_melanogaster	CG31075	FBGN0051075
caenorhabditis_elegans		WBGENE00000107
caenorhabditis_elegans		WBGENE00000108
caenorhabditis_elegans		WBGENE00000109

Paralogs (17): ALDH3B1 (ENSG00000006534), ALDH3A2 (ENSG00000072210), ALDH3A1 (ENSG00000108602), ALDH2 (ENSG00000111275), ALDH5A1 (ENSG00000112294), ALDH8A1 (ENSG00000118514), ALDH6A1 (ENSG00000119711), ALDH1A2 (ENSG00000128918), ALDH3B2 (ENSG00000132746), ALDH1L2 (ENSG00000136010), ALDH1B1 (ENSG00000137124), ALDH9A1 (ENSG00000143149), ALDH1L1 (ENSG00000144908), ALDH4A1 (ENSG00000159423), ALDH16A1 (ENSG00000161618), ALDH7A1 (ENSG00000164904), ALDH1A3 (ENSG00000184254)

Protein

Protein identifiers

Aldehyde dehydrogenase 1A1 — P00352 (reviewed: P00352)

Alternative names: 3-deoxyglucosone dehydrogenase, ALDH-E1, ALHDII, Aldehyde dehydrogenase family 1 member A1, Aldehyde dehydrogenase, cytosolic, Retinal dehydrogenase 1

All UniProt accessions (5): P00352, Q5SYQ7, Q5SYQ8, Q5SYQ9, V9HW83

UniProt curated annotations — full annotation on UniProt →

Function. Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid. 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. Also functions 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. Also has 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.

Subunit / interactions. Homotetramer. Interacts with PRMT3; the interaction is direct, inhibits ALDH1A1 aldehyde dehydrogenase activity and is independent of the methyltransferase activity of PRMT3.

Subcellular location. Cytoplasm. Cytosol. Cell projection. Axon.

Tissue specificity. Expressed by erythrocytes (at protein level).

Post-translational modifications. The N-terminus is blocked most probably by acetylation.

Activity regulation. Inhibited by citral, disulfiram, and cyanamide. Activated by diethylstilbestrol. Inhibited by duocarmycin analogs.

Pathway. Cofactor metabolism; retinol metabolism.

Similarity. Belongs to the aldehyde dehydrogenase family.

RefSeq proteins (1): NP_000680* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015590	Aldehyde_DH_dom	Domain
IPR016160	Ald_DH_CS_CYS	Conserved_site
IPR016161	Ald_DH/histidinol_DH	Homologous_superfamily
IPR016162	Ald_DH_N	Homologous_superfamily
IPR016163	Ald_DH_C	Homologous_superfamily
IPR029510	Ald_DH_CS_GLU	Conserved_site

Pfam: PF00171

Enzyme classification (BRENDA):

• EC 1.2.1.36 — retinal dehydrogenase (BRENDA: 12 organisms, 91 substrates, 181 inhibitors, 94 Km, 24 kcat entries)

Substrate kinetics (BRENDA)

23 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ALL-TRANS-RETINAL	0.0002–0.015	14
ACETALDEHYDE	0.014–3.4	12
RETINAL	0.0007–0.76	12
NAD+	0.022–0.39	10
HEXANAL	0.0003–0.023	6
9-CIS-RETINAL	0.0022–0.0087	5
DECANAL	0.0003–0.01	5
OCTANAL	0.0003–0.01	5
BENZALDEHYDE	0.0003–0.103	3
13-CIS-RETINAL	0.0006	2
ALL-TRANS RETINAL	0.0039	2
BETA-APO-12’-CAROTENAL	0.0018–0.003	2
BETA-APO-14’-CAROTENAL	0.005–0.012	2
13-CIS RETINAL	0.0034	1
2,4-DECADIENAL	0.0063	1

Catalyzed reactions (Rhea), 12 shown:

• benzaldehyde + NAD(+) + H2O = benzoate + NADH + 2 H(+) (RHEA:11840)
• an aldehyde + NAD(+) + H2O = a carboxylate + NADH + 2 H(+) (RHEA:16185)
• 4-aminobutanal + NAD(+) + H2O = 4-aminobutanoate + NADH + 2 H(+) (RHEA:19105)
• acetaldehyde + NAD(+) + H2O = acetate + NADH + 2 H(+) (RHEA:25294)
• all-trans-retinal + NAD(+) + H2O = all-trans-retinoate + NADH + 2 H(+) (RHEA:42080)
• 9-cis-retinal + NAD(+) + H2O = 9-cis-retinoate + NADH + 2 H(+) (RHEA:42084)
• 11-cis-retinal + NAD(+) + H2O = 11-cis-retinoate + NADH + 2 H(+) (RHEA:47132)
• 3-deoxyglucosone + NAD(+) + H2O = 2-dehydro-3-deoxy-D-gluconate + NADH + 2 H(+) (RHEA:67244)
• (E)-4-hydroxynon-2-enal + NAD(+) + H2O = (E)-4-hydroxynon-2-enoate + NADH + 2 H(+) (RHEA:67248)
• malonaldehyde + NAD(+) + H2O = 3-oxopropanoate + NADH + 2 H(+) (RHEA:67252)
• propanal + NAD(+) + H2O = propanoate + NADH + 2 H(+) (RHEA:67256)
• hexanal + NAD(+) + H2O = hexanoate + NADH + 2 H(+) (RHEA:67276)

UniProt features (81 total): strand 27, helix 21, modified residue 12, binding site 7, sequence variant 3, mutagenesis site 2, active site 2, turn 2, initiator methionine 1, chain 1, site 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

24 structures.

PDB	Method	Resolution (Å)
7JWS	X-RAY DIFFRACTION	1.6
7JWV	X-RAY DIFFRACTION	1.6
7JWW	X-RAY DIFFRACTION	1.6
5L2M	X-RAY DIFFRACTION	1.7
5L2N	X-RAY DIFFRACTION	1.7
4WJ9	X-RAY DIFFRACTION	1.74
8T0T	X-RAY DIFFRACTION	1.75
4WP7	X-RAY DIFFRACTION	1.8
7JWT	X-RAY DIFFRACTION	1.8
7UM9	X-RAY DIFFRACTION	1.8
4X4L	X-RAY DIFFRACTION	1.85
5AC2	X-RAY DIFFRACTION	1.85
8T0N	X-RAY DIFFRACTION	1.86
7JWU	X-RAY DIFFRACTION	1.9
4WPN	X-RAY DIFFRACTION	1.95
6DUM	X-RAY DIFFRACTION	2
5L2O	X-RAY DIFFRACTION	2.05
4WB9	X-RAY DIFFRACTION	2.07
5TEI	X-RAY DIFFRACTION	2.1
8ENE	ELECTRON MICROSCOPY	2.64
8D46	ELECTRON MICROSCOPY	2.84
8PVH	ELECTRON MICROSCOPY	2.9
8DNO	ELECTRON MICROSCOPY	3.4
8WFQ	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00352-F1	97.96	0.98

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 170 (transition state stabilizer); 269 (proton acceptor); 303 (nucleophile)

Ligand- & substrate-binding residues (7): 349–353; 400–402; 167–170; 193–196; 226–227; 246–247; 269–271

Post-translational modifications (12): 2, 91, 128, 252, 337, 353, 367, 410, 413, 419, 435, 495

Mutagenesis-validated functional residues (2):

Position	Phenotype
302	does not prevent inhibition by duocarmycin analogs.
458	no significant effect on aldehyde dehydrogenase activity. prevents the inhibition by aldh1a1-specific inhibitors.

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-5365859	RA biosynthesis pathway
R-HSA-70350	Fructose catabolism
R-HSA-71384	Ethanol oxidation
R-HSA-9927418	Developmental Lineage of Mammary Gland Luminal Epithelial Cells
R-HSA-9927432	Developmental Lineage of Mammary Gland Myoepithelial Cells
R-HSA-9938206	Developmental Lineage of Mammary Stem Cells
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-211859	Biological oxidations
R-HSA-211945	Phase I - Functionalization of compounds
R-HSA-5362517	Signaling by Retinoic Acid
R-HSA-5652084	Fructose metabolism
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives
R-HSA-9006931	Signaling by Nuclear Receptors

MSigDB gene sets: 404 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, MODULE_93, MODULE_52, REACTOME_BIOLOGICAL_OXIDATIONS, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GRUETZMANN_PANCREATIC_CANCER_DN, DORSAM_HOXA9_TARGETS_UP, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_REGULATION_OF_HORMONE_LEVELS, AREB6_01, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN

GO Biological Process (9): retinoid metabolic process (GO:0001523), aldehyde metabolic process (GO:0006081), GABA biosynthetic process (GO:0009449), fructosamine catabolic process (GO:0030392), maintenance of lens transparency (GO:0036438), retinol metabolic process (GO:0042572), cellular detoxification of aldehyde (GO:0110095), negative regulation of cold-induced thermogenesis (GO:0120163), lipid metabolic process (GO:0006629)

GO Molecular Function (13): retinal dehydrogenase (NAD+) activity (GO:0001758), aldehyde dehydrogenase (NAD+) activity (GO:0004029), GTPase activator activity (GO:0005096), androgen binding (GO:0005497), benzaldehyde dehydrogenase (NAD+) activity (GO:0018479), aminobutyraldehyde dehydrogenase (NAD+) activity (GO:0019145), NAD binding (GO:0051287), 3-deoxyglucosone dehydrogenase activity (GO:0106373), acetaldehyde dehydrogenase (NAD+) activity (GO:0140087), nucleotide binding (GO:0000166), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor (GO:0016620)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), axon (GO:0030424), synapse (GO:0045202), extracellular exosome (GO:0070062), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Developmental Lineages of the Mammary Gland	3
Metabolism	2
Signaling by Retinoic Acid	1
Fructose metabolism	1
Phase I - Functionalization of compounds	1
Biological oxidations	1
Signaling by Nuclear Receptors	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
aldehyde dehydrogenase (NAD+) activity	5
cellular anatomical structure	3
diterpenoid metabolic process	1
metabolic process	1
amino acid biosynthetic process	1
non-proteinogenic amino acid biosynthetic process	1
fructosamine metabolic process	1
amino sugar catabolic process	1
tissue homeostasis	1
retinoid metabolic process	1
primary alcohol metabolic process	1
hormone metabolic process	1
olefinic compound metabolic process	1
cellular response to aldehyde	1
cellular detoxification	1
negative regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
primary metabolic process	1
aldehyde dehydrogenase [NAD(P)+] activity	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
hormone binding	1
adenyl nucleotide binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on the aldehyde or oxo group of donors	1
intracellular anatomical structure	1
cytoplasm	1
neuron projection	1
cell junction	1
extracellular vesicle	1

Protein interactions and networks

STRING

5136 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALDH1A1	PROM1	O43490	872
ALDH1A1	ADH1A	P07327	853
ALDH1A1	CD44	P16070	840
ALDH1A1	ADH4	P08319	822
ALDH1A1	CD24	P25063	815
ALDH1A1	ADH1B	P00325	814
ALDH1A1	NANOG	Q9H9S0	771
ALDH1A1	SOX2	P48431	770
ALDH1A1	RBP1	P09455	746
ALDH1A1	ADH7	P40394	741
ALDH1A1	POU5F1	P31359	739
ALDH1A1	AVP	P01185	739
ALDH1A1	ABCG2	Q9UNQ0	728
ALDH1A1	EPCAM	P16422	719
ALDH1A1	IDH1	O75874	707

IntAct

58 interactions, top by confidence:

A	B	Type	Score
ALDH1A1	DBH	psi-mi:“MI:0915”(physical association)	0.560
ALDH1A1	GFAP	psi-mi:“MI:0915”(physical association)	0.560
ALDH1A1	JPH3	psi-mi:“MI:0915”(physical association)	0.560
ALDH1A1	ALDH1A1	psi-mi:“MI:0915”(physical association)	0.550
ALDH2	ALDH1A1	psi-mi:“MI:0915”(physical association)	0.490
ALDH1A1	ALDH2	psi-mi:“MI:0915”(physical association)	0.490
IL21	ALDH1A1	psi-mi:“MI:0915”(physical association)	0.400
CHN1	ALDH1A1	psi-mi:“MI:0915”(physical association)	0.400
ALDH1A1	PI4K2A	psi-mi:“MI:0915”(physical association)	0.400
PIP5K1A	ALDH1A1	psi-mi:“MI:0915”(physical association)	0.400
ALDH1A1	ALDH1A2	psi-mi:“MI:0915”(physical association)	0.400
POT1	ALDH1A1	psi-mi:“MI:0915”(physical association)	0.370
NUPR1	ALDH1A1	psi-mi:“MI:0915”(physical association)	0.370
PB1	HAX1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
INPPL1	ACTN4	psi-mi:“MI:0914”(association)	0.350
PIK3C2A	ACTN4	psi-mi:“MI:0914”(association)	0.350
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
OR13C3	POTEF	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
RIPPLY3	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (62): ALDH1A1 (Two-hybrid), ALDH1A1 (Two-hybrid), ALDH1A1 (Affinity Capture-MS), ALDH1A1 (Affinity Capture-MS), ALDH1A1 (Affinity Capture-MS), ALDH1A1 (Affinity Capture-MS), ALDH1A1 (Proximity Label-MS), ALDH1A1 (Affinity Capture-MS), ALDH1A1 (Affinity Capture-MS), ALDH1A1 (Affinity Capture-MS), ALDH1A1 (Affinity Capture-MS), ALDH1A1 (Affinity Capture-MS), ALDH1A1 (Affinity Capture-MS), ALDH1A1 (Affinity Capture-MS), ALDH1A1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0E3T3B5, A0A0E3T552, A0A2I7G3B0, A5WA96, B0KN18, B1J2K9, B6ECN9, B7M2V6, C5I9X1, O14293, O35945, O74187, O93344, O94788, P00352, P08157, P12762, P13601, P17202, P27463, P28237, P40108, P41751, P42041, P42757, P54115, P71016, P81178, P86886, Q25417, Q27640, Q28399, Q29490, Q3K5H4, Q48CM6, Q4K4K8, Q4ZM62, Q56R04, Q56YU0, Q62148

Diamond homologs: A0A0E3T3B5, A0A0E3T552, A0A2I7G3B0, A0B2F6, A4JJG5, A4VKC2, A4XPI6, A5WA96, A6VEI4, A6ZR27, A8GBX8, A9AN00, B0KN18, B1J2K9, B1JSQ9, B1K708, B1Z033, B2FQ90, B3VMC0, B4EHJ1, B6ECN9, B7V5R4, C0P9J6, C3K3D2, C5I9X1, C6DKY5, C6KEM4, G5DDC2, H8ZPX2, O04895, O14293, O24174, O34660, O35945, O59808, O74187, O93344, O94788, P00352, P05091

SIGNOR signaling

14 interactions.

A	Effect	B	Mechanism
EZH2	“down-regulates quantity by repression”	ALDH1A1	“transcriptional regulation”
ALDH1A1	“down-regulates quantity”	retinal	“chemical modification”
ALDH1A1	“up-regulates quantity”	“all-trans-retinoic acid”	“chemical modification”
PRMT3	“down-regulates activity”	ALDH1A1	binding
AURKA	“up-regulates quantity”	ALDH1A1	phosphorylation
CDK5	“up-regulates quantity”	ALDH1A1	phosphorylation
ALDH1A1	“down-regulates quantity”	D-glyceraldehyde	“chemical modification”
ALDH1A1	“up-regulates quantity”	D-glycerate	“chemical modification”
AURKA	“up-regulates activity”	ALDH1A1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

57 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	36
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
59108	GRCh38/hg38 9q21.13-21.2(chr9:72224348-77332127)x1	Pathogenic

SpliceAI

1416 predictions. Top by Δscore:

Variant	Effect	Δscore
9:72905956:A:AC	donor_gain	1.0000
9:72905957:C:CC	donor_gain	1.0000
9:72905957:CAGTT:C	donor_gain	1.0000
9:72906031:CC:C	acceptor_gain	1.0000
9:72906032:CC:C	acceptor_gain	1.0000
9:72909594:GGACT:G	donor_loss	1.0000
9:72909595:GACTT:G	donor_loss	1.0000
9:72909596:ACT:A	donor_loss	1.0000
9:72909597:CTTA:C	donor_loss	1.0000
9:72909598:TTACC:T	donor_loss	1.0000
9:72909599:T:TC	donor_loss	1.0000
9:72909600:A:AA	donor_loss	1.0000
9:72909600:A:AC	donor_gain	1.0000
9:72909601:C:CC	donor_gain	1.0000
9:72909601:CCA:C	donor_gain	1.0000
9:72909601:CCACA:C	donor_gain	1.0000
9:72909757:AATC:A	acceptor_loss	1.0000
9:72909759:TC:T	acceptor_loss	1.0000
9:72909760:C:CA	acceptor_loss	1.0000
9:72909760:C:CC	acceptor_gain	1.0000
9:72909766:C:CT	acceptor_gain	1.0000
9:72911953:TTTA:T	donor_loss	1.0000
9:72911954:TTA:T	donor_loss	1.0000
9:72911955:TAC:T	donor_loss	1.0000
9:72911956:A:T	donor_loss	1.0000
9:72911956:ACCT:A	donor_gain	1.0000
9:72911957:C:G	donor_loss	1.0000
9:72911957:CCTC:C	donor_gain	1.0000
9:72911959:T:TA	donor_gain	1.0000
9:72912119:CAAT:C	acceptor_gain	1.0000

AlphaMissense

3273 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:72905973:C:T	G473E	0.999
9:72909754:A:C	F402L	0.999
9:72909754:A:T	F402L	0.999
9:72909756:A:G	F402L	0.999
9:72918761:A:G	L270P	0.999
9:72924029:C:T	G246E	0.999
9:72925607:A:C	N170K	0.999
9:72925607:A:T	N170K	0.999
9:72909752:C:T	G403E	0.998
9:72918748:G:C	S274R	0.998
9:72918748:G:T	S274R	0.998
9:72918750:T:G	S274R	0.998
9:72918818:C:T	G251D	0.998
9:72924034:G:C	F244L	0.998
9:72924034:G:T	F244L	0.998
9:72924036:A:G	F244L	0.998
9:72924101:A:T	V222D	0.998
9:72925538:T:A	K193N	0.998
9:72925538:T:G	K193N	0.998
9:72925540:T:C	K193E	0.998
9:72925545:A:T	V191D	0.998
9:72930962:A:G	W77R	0.998
9:72930962:A:T	W77R	0.998
9:72905973:C:A	G473V	0.997
9:72905976:G:A	S472F	0.997
9:72905988:C:T	G468E	0.997
9:72909672:C:G	A430P	0.997
9:72909680:C:T	G427D	0.997
9:72911998:A:G	F387S	0.997
9:72912001:A:T	V386E	0.997

dbSNP variants (sampled 300 via entrez): RS1000006795 (9:72906448 A>C), RS1000037475 (9:72942653 C>T), RS1000173214 (9:72950275 G>A), RS1000282660 (9:72920494 T>G), RS1000304706 (9:72939039 G>A,T), RS1000415650 (9:72939314 T>A), RS1000594311 (9:72925555 T>C), RS1000708669 (9:72925870 C>G), RS1000717684 (9:72941604 C>A,T), RS1000735238 (9:72917093 C>T), RS1000902207 (9:72911889 A>G,T), RS1000930370 (9:72932342 T>A), RS1001016677 (9:72912244 C>G,T), RS1001131237 (9:72905092 G>A), RS1001179748 (9:72918592 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST008360_3	Response to cognitive-behavioural therapy in anxiety disorder	4.000000e-06
GCST009310_26	Sensorimotor dexterity	9.000000e-06
GCST009799_4	Alcohol consumption (drinkers vs non-drinkers)	5.000000e-14
GCST010002_321	Refractive error	6.000000e-36

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy
EFO:0008354	cognitive function measurement
EFO:0004329	alcohol drinking

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3542434 (PROTEIN FAMILY), CHEMBL3577 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

468 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 779,723 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL101	PHENYLBUTAZONE	4	59,455
CHEMBL1017	TELMISARTAN	4	27,457
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL1042	CHOLECALCIFEROL	4	64,162
CHEMBL1046	AMINOCAPROIC ACID	4	95,343
CHEMBL1065	METHYSERGIDE	4	8,455
CHEMBL1068	OXCARBAZEPINE	4	16,118
CHEMBL1072	BUMETANIDE	4	22,087
CHEMBL1082607	SALMETEROL XINAFOATE	4	15,201
CHEMBL1083993	AMIODARONE HYDROCHLORIDE	4	3,265
CHEMBL1086	DIBUCAINE	4	17,231
CHEMBL1089	PHENELZINE	4	18,793
CHEMBL1091250	INDIGOTINDISULFONATE	4	340
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1103	FURAZOLIDONE	4	14,492
CHEMBL110691	CHLORMADINONE ACETATE	4	9,747
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1116	RALOXIFENE HYDROCHLORIDE	4	28,574
CHEMBL1117	IDARUBICIN	4	136,065
CHEMBL112	ACETAMINOPHEN	4
CHEMBL1131	ACITRETIN	4
CHEMBL11359	CISPLATIN	4
CHEMBL1139	EPOPROSTENOL	4
CHEMBL1159	PINACIDIL ANHYDROUS	4
CHEMBL117785	TETRABENAZINE	4
CHEMBL119	TRIMETREXATE	4
CHEMBL1191	SULFAMETHIZOLE	4
CHEMBL1198	PRAMOXINE	4
CHEMBL1200323	LABETALOL HYDROCHLORIDE	4

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs6151031	Toxicity	3	carboplatin;cyclophosphamide;thiotepa
rs6151031	Efficacy	3	cyclophosphamide;doxorubicin	Breast Neoplasms

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs63319	ALDH1A1		0.00	0
rs168351	ALDH1A1		0.00	0
rs3764435	ALDH1A1		0.00	0
rs6151031	ALDH1A1	3	3.00	2	cyclophosphamide;doxorubicin;carboplatin;cyclophosphamide;thiotepa
rs8187996	ALDH1A1		0.00	0
rs13959	ALDH1A1		0.00	0

Binding affinities (BindingDB)

15 measured of 21 human assays (21 total across all organisms); most potent 15 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
ethyl 2-[3-hydroxy-2-oxo-3-(2-oxo-2-pyridin-2-ylethyl)indol-1-yl]acetate	IC50	700 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
ethyl 2-[3-hydroxy-2-oxo-3-(2-oxo-2-pyridin-4-ylethyl)indol-1-yl]acetate	IC50	800 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
N-(1-hydroxy-2-oxo-2-thiophen-2-ylethyl)-4-methylbenzenesulfonamide	IC50	4000 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
N-(1-hydroxy-2-oxo-2-thiophen-2-ylethyl)pyridine-4-carboxamide	IC50	4200 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
[ethyl-[[4-(trifluoromethyl)phenyl]methyl]carbamothioyl]sulfanyl N-ethyl-N-[[4-(trifluoromethyl)phenyl]methyl]carbamodithioate	IC50	5760 nM	US-20250145565: DITHIENYL DISULFIRAM DERIVATIVES AS SELECTIVE ALDH1A1 INHIBITORS
N-(1-hydroxy-2-oxo-2-thiophen-2-ylethyl)pyridine-3-carboxamide	IC50	5900 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
3-ethyl-4-(3-fluoro-4-methoxyphenyl)-N-phenyl-1,3-thiazol-2-imine	IC50	6300 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
2-phenylspiro[1,10b-dihydropyrazolo[1,5-c][1,3]benzoxazine-5,3’-1H-indole]-2’-one	IC50	6500 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
(3-ethylsulfanyl-6,7-dihydro-[1,2,4]triazino[5,6-d][3,1]benzoxazepin-6-yl)-(4-methoxyphenyl)methanone	IC50	8200 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
5-acetyl-2-[2-(4-bromophenyl)-2-oxoethyl]sulfanyl-6-methyl-4-propyl-1,4-dihydropyridine-3-carbonitrile	IC50	10400 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
3-methyl-N-[4-[4-(methylsulfamoyl)-2-nitroanilino]phenyl]butanamide	IC50	11600 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
2-methyl-N-[4-(4-methylsulfonyl-2-nitroanilino)phenyl]propanamide	IC50	16800 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
(4-methoxyphenyl)-(3-propylsulfanyl-6,7-dihydro-[1,2,4]triazino[5,6-d][3,1]benzoxazepin-6-yl)methanone	IC50	21200 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
2-[4-(2,5-dichlorophenyl)sulfonylpiperazin-1-yl]-1-(3-methylphenyl)ethanone	IC50	33000 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
2-(4-methylsulfonyl-2-nitroanilino)propanoic acid	IC50	50000 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.49	Potency	3.2	nM	CHEMBL1607827
8.46	Potency	3.5	nM	CHEMBL1498452
8.35	Potency	4.5	nM	CHEMBL600769
8.35	Potency	4.5	nM	CHEMBL1542395
8.35	Potency	4.5	nM	VANCOMYCIN HYDROCHLORIDE
8.30	IC50	5	nM	CHEMBL4207222
8.30	Potency	5	nM	CHEMBL1576608
8.30	Potency	5	nM	CHEMBL1441067
8.30	Potency	5	nM	CHEMBL2369196
8.26	Ki	5.5	nM	CHEMBL4206892
8.25	Potency	5.6	nM	CHEMBL1300462
8.25	Potency	5.6	nM	CHEMBL1328800
8.25	Potency	5.6	nM	CHEMBL1361393
8.25	Potency	5.6	nM	CHEMBL1376427
8.22	IC50	6	nM	CHEMBL4212671
8.22	IC50	6	nM	CHEMBL4207514
8.22	IC50	6	nM	CHEMBL4211904
8.22	IC50	6	nM	CHEMBL4215704
8.22	Potency	6	nM	CHEMBL3189457
8.19	IC50	6.5	nM	CHEMBL4206892
8.15	IC50	7	nM	CHEMBL4209722
8.15	IC50	7	nM	CHEMBL4207617
8.15	IC50	7	nM	CHEMBL4206606
8.15	IC50	7	nM	CHEMBL4202680
8.15	IC50	7	nM	CHEMBL4206272
8.15	IC50	7	nM	CHEMBL4206892
8.15	Potency	7.1	nM	CHEMBL1492006
8.15	Potency	7.1	nM	CHEMBL1336893
8.14	Ki	7.2	nM	CHEMBL4206272
8.12	Potency	7.5	nM	CHEMBL1327135
8.10	IC50	8	nM	CHEMBL4212891
8.10	IC50	8	nM	CHEMBL4218688
8.10	IC50	8	nM	CHEMBL4213848
8.10	Potency	7.9	nM	CHEMBL1489143
8.10	Potency	7.9	nM	CHEMBL1507858
8.05	IC50	9	nM	CHEMBL4213604
8.05	IC50	9	nM	CHEMBL4217115
8.05	IC50	9	nM	CHEMBL4214724
8.05	Potency	8.9	nM	CHEMBL3189647
8.05	Potency	8.9	nM	KHELLIN
8.05	Potency	8.9	nM	CHEMBL1355293
8.05	Potency	8.9	nM	CHEMBL1575066
8.04	IC50	9.2	nM	CHEMBL4206892
8.00	IC50	10	nM	CHEMBL4207953
8.00	IC50	10	nM	CHEMBL4210671
8.00	IC50	10	nM	CHEMBL115581
8.00	Potency	10	nM	CHEMBL1330916
8.00	Potency	10	nM	CHEMBL1509142
7.96	IC50	11	nM	CHEMBL4215957
7.96	IC50	11	nM	CHEMBL4205368

PubChem BioAssay actives

433 with measured affinity, of 805 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[4-[7-methoxy-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]phenyl]cyclopropane-1-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0050	uM
1-[6-fluoro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]-4-phenylpiperidine-4-carbonitrile	1375893: Inhibition of human ALDH1A1 using propionaldehyde as substrate and varied concentration of NAD+ as cofactor preincubated for 15 mins followed by substrate addition measured for 30 mins by fluorescence assay	ki	0.0055	uM
4-[4-[4-(1-cyanocyclopropyl)phenyl]-6-fluoroquinoline-3-carbonyl]-N,N-dimethylpiperazine-1-sulfonamide	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0060	uM
1-[4-[3-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]-6-fluoroquinolin-4-yl]phenyl]cyclopropane-1-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0060	uM
2-[4-[3-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]-6-fluoroquinolin-4-yl]phenyl]-2-methylpropanenitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0060	uM
4-[4-(4-cyano-4-phenylpiperidin-1-yl)-6-fluoroquinoline-3-carbonyl]-N,N-dimethylpiperazine-1-carboxamide	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0060	uM
1-[4-[6-fluoro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]phenyl]cyclopropane-1-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0070	uM
1-[4-[6-chloro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]phenyl]cyclopropane-1-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0070	uM
1-[6-fluoro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]-4-(2-fluorophenyl)piperidine-4-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0070	uM
1-[4-[6-methoxy-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]phenyl]cyclopropane-1-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0070	uM
1-[4-[6-fluoro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]phenyl]cyclobutane-1-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0070	uM
4-[4-[4-(1-cyanocyclopropyl)phenyl]-6-fluoroquinoline-3-carbonyl]-N,N-dimethylpiperazine-1-carboxamide	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0080	uM
1-[3-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]-6-fluoroquinolin-4-yl]-4-phenylpiperidine-4-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0080	uM
1-[4-[6,7-difluoro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]phenyl]cyclopropane-1-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0080	uM
2-[3-fluoro-4-[6-fluoro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]phenyl]-2-methylpropanenitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0090	uM
2-[4-[6-fluoro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]phenyl]-2-methylpropanenitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0090	uM
1-[4-[6,8-difluoro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]phenyl]cyclopropane-1-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0090	uM
1-[6-fluoro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]-4-phenylpiperidine-4-carbaldehyde	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0100	uM
1-[6-(4-methylsulfonylpiperazine-1-carbonyl)thieno[3,2-b]pyridin-7-yl]-4-phenylpiperidine-4-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0100	uM
1-benzylindole-2,3-dione	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0100	uM
1-[1-[6-fluoro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]-4-phenylpiperidin-4-yl]ethanone	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0110	uM
1-[6-fluoro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]-4-(4-fluorophenyl)piperidine-4-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0110	uM
1-[6,8-difluoro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]-4-phenylpiperidine-4-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0110	uM
1-[6,7-difluoro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]-4-phenylpiperidine-4-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0120	uM
1-[6-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]thieno[3,2-b]pyridin-7-yl]-4-phenylpiperidine-4-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0120	uM
1-[6-methoxy-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]-4-phenylpiperidine-4-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0120	uM
4-ethyl-1-[6-fluoro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]piperidine-4-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0120	uM
[4-(4-tert-butylphenyl)-6-fluoroquinolin-3-yl]-(4-methylsulfonylpiperazin-1-yl)methanone	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0120	uM
[4-[6-chloro-4-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)quinoline-3-carbonyl]piperazin-1-yl]-cyclopropylmethanone	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0130	uM
1-[3-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]-6-fluoroquinolin-4-yl]-4-(cyclopropylmethyl)piperidine-4-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0130	uM
cyclopropyl-[4-[4-(4,4-dimethylcyclohexen-1-yl)-6-fluoroquinoline-3-carbonyl]piperazin-1-yl]methanone	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0130	uM
1-[4-[6-chloro-3-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]quinolin-4-yl]phenyl]cyclopropane-1-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0130	uM
[4-[4-(4-tert-butylphenyl)-6-fluoroquinoline-3-carbonyl]piperazin-1-yl]-cyclopropylmethanone	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0140	uM
1-[6-chloro-3-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]quinolin-4-yl]-4-phenylpiperidine-4-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0140	uM
4-[4-(4-cyano-4-phenylpiperidin-1-yl)-6-fluoroquinoline-3-carbonyl]-N,N-dimethylpiperazine-1-sulfonamide	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0140	uM
1-[7-methoxy-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]-4-phenylpiperidine-4-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0140	uM
1-[4-[6-fluoro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]phenyl]cyclopentane-1-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0140	uM
1-[3-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]-6-fluoroquinolin-4-yl]-4-ethylpiperidine-4-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0150	uM
1-[6-chloro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]-4-phenylpiperidine-4-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0150	uM
1-[3-fluoro-4-[6-fluoro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]phenyl]cyclopropane-1-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0160	uM
8-[6-methoxy-3-(4-methoxyphenyl)sulfonylquinolin-4-yl]-1,4-dioxa-8-azaspiro[4.5]decane	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0170	uM
1-[4-[6-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]thieno[3,2-b]pyridin-7-yl]phenyl]cyclopropane-1-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0170	uM
1-[6-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]thieno[3,2-b]pyridin-7-yl]-4-methylpiperidine-4-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0170	uM
1’-[6-fluoro-3-(4-methylsulfonylpiperazine-1-carbonyl)quinolin-4-yl]spiro[1H-indene-3,4’-piperidine]-2-one	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0180	uM
cyclopropyl-[4-[4-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-6-methoxyquinoline-3-carbonyl]piperazin-1-yl]methanone	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0190	uM
cyclopropyl-[4-[4-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-6-fluoroquinoline-3-carbonyl]piperazin-1-yl]methanone	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0190	uM
[4-[4-(3-azaspiro[5.5]undecan-3-yl)-6-fluoroquinoline-3-carbonyl]piperazin-1-yl]-cyclopropylmethanone	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0190	uM
1-[4-[6-(4-methylsulfonylpiperazine-1-carbonyl)thieno[3,2-b]pyridin-7-yl]phenyl]cyclopropane-1-carbonitrile	1375824: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay	ic50	0.0200	uM
ethyl 2-[[4-oxo-3-(3-pyrrolidin-1-ylpropyl)-[1]benzothiolo[3,2-d]pyrimidin-2-yl]sulfanyl]acetate	1646925: Inhibition of ALDH1A (unknown origin)	ic50	0.0200	uM
dimethylcarbamothioylsulfanyl N,N-dimethylcarbamodithioate	1762210: Inhibition of ALDH1A1 (unknown origin)	ic50	0.0200	uM

CTD chemical–gene interactions

159 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases oxidation, affects cotreatment, decreases activity, decreases reaction, affects binding	5
Cyclosporine	affects cotreatment, affects expression, decreases expression	5
sodium arsenite	increases expression	4
Benzo(a)pyrene	increases expression, increases reaction, decreases expression, increases methylation	4
NAD	increases reduction, increases oxidation, affects cotreatment, increases activity, decreases activity (+2 more)	4
bisphenol A	affects expression, decreases expression, increases expression	3
cobaltous chloride	decreases expression	3
4-(diethylamino)benzaldehyde	decreases activity, increases oxidation, decreases reaction, decreases response to substance	3
Cisplatin	affects reaction, decreases expression, decreases response to substance, increases expression	3
Cyclophosphamide	affects response to substance, decreases response to substance, increases expression	3
Disulfiram	decreases expression, decreases reaction, decreases response to substance, decreases activity	3
Ethinyl Estradiol	affects expression, decreases expression	3
Tretinoin	affects cotreatment, increases chemical synthesis, decreases activity, decreases expression	3
Valproic Acid	decreases expression, decreases methylation, increases expression	3
Cadmium Chloride	decreases expression, increases expression	3
aldophosphamide	affects cotreatment, increases oxidation	2
titanium dioxide	increases phosphorylation, affects binding, decreases expression	2
salinomycin	decreases expression	2
perfosfamide	decreases response to substance	2
sulforaphane	affects binding, decreases expression, increases reaction	2
enilconazole	decreases expression, increases activity, affects cotreatment	2
diallyl trisulfide	decreases reaction, increases expression, decreases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
cyproconazole	decreases expression, increases activity	2
Arsenic Trioxide	affects binding, decreases reaction, decreases expression	2
Acetaldehyde	decreases reaction, increases oxidation	2
Acetaminophen	decreases expression	2
Hydrogen Peroxide	affects expression	2
Nickel	decreases expression	2
Phenobarbital	increases expression	2

ChEMBL screening assays

105 unique, capped per target: 100 binding, 4 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1019415	Binding	Effect on human recombinant his-tagged cytosolic ALDH1A1 activity expressed in Escherichia coli BL21 cells at 100 uM	Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. — Science
CHEMBL1614458	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of Aldehyde Dehydrogenase 1 (ALDH1A1). (Class of assay: confirmatory) [Related pubchem assays: 1030 (qHTS Validation Assay for Inhibitors of aldehyde dehydrogenase 1 (ALDH1A1))]	PubChem BioAssay data set
CHEMBL5049237	ADMET	Substrate activity at N-terminal-His6 tagged recombinant human ALDH1A1 at 10 uM in presence of NADH by fluorimetric analysis relative to hexanal	Expansion of the 4-(Diethylamino)benzaldehyde Scaffold to Explore the Impact on Aldehyde Dehydrogenase Activity and Antiproliferative Activity in Prostate Cancer. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2M1	Abcam A-549 ALDH1A1 KO	Cancer cell line	Male
CVCL_D1RK	Abcam U-87MG ALDH1A1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.