ALDH1A2

Summary

ALDH1A2 (aldehyde dehydrogenase 1 family member A2, HGNC:15472) is a protein-coding gene on chromosome 15q21.3, encoding Retinal dehydrogenase 2 (O94788). Catalyzes the NAD-dependent oxidation of aldehyde substrates, such as all-trans-retinal and all-trans-13,14-dihydroretinal, to their corresponding carboxylic acids, all-trans-retinoate and all-trans-13,14-dihydroretinoate, respectively. In precision oncology, ALDH1A2 Underexpression confers sensitivity to Tretinoin in Head And Neck Squamous Cell Carcinoma (CIViC Level D).

This protein belongs to the aldehyde dehydrogenase family of proteins. The product of this gene is an enzyme that catalyzes the synthesis of retinoic acid (RA) from retinaldehyde. Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal signaling molecule that functions in developing and adult tissues. The studies of a similar mouse gene suggest that this enzyme and the cytochrome CYP26A1, concurrently establish local embryonic retinoic acid levels which facilitate posterior organ development and prevent spina bifida. Four transcript variants encoding distinct isoforms have been identified for this gene.

Source: NCBI Gene 8854 — RefSeq curated summary.

At a glance

• Gene–disease (curated): diaphragmatic hernia 4, with cardiovascular defects (Strong, GenCC)
• GWAS associations: 56
• Clinical variants (ClinVar): 91 total — 5 pathogenic
• Phenotypes (HPO): 30
• Druggable target: yes
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_003888

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15472
Approved symbol	ALDH1A2
Name	aldehyde dehydrogenase 1 family member A2
Location	15q21.3
Locus type	gene with protein product
Status	Approved
Aliases	RALDH2
Ensembl gene	ENSG00000128918
Ensembl biotype	protein_coding
OMIM	603687
Entrez	8854

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 14 protein_coding_CDS_not_defined, 12 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000249750, ENST00000347587, ENST00000430119, ENST00000537372, ENST00000557967, ENST00000558073, ENST00000558231, ENST00000558239, ENST00000558384, ENST00000558504, ENST00000558524, ENST00000558595, ENST00000558603, ENST00000558946, ENST00000559266, ENST00000559297, ENST00000559517, ENST00000559579, ENST00000559625, ENST00000560122, ENST00000560312, ENST00000560863, ENST00000560923, ENST00000561070, ENST00000561098, ENST00000888709, ENST00000888710, ENST00000888711, ENST00000945725

RefSeq mRNA: 4 — MANE Select: NM_003888 NM_001206897, NM_003888, NM_170696, NM_170697

CCDS: CCDS10163, CCDS10164, CCDS45266, CCDS55968

Canonical transcript exons

ENST00000249750 — 13 exons

Exon	Start	End
ENSE00001415367	58065534	58065711
ENSE00003497088	57960770	57960844
ENSE00003515743	58014177	58014281
ENSE00003542135	58013858	58013998
ENSE00003551802	57963885	57964069
ENSE00003563479	57995078	57995139
ENSE00003595949	57961137	57961294
ENSE00003607946	57992705	57992818
ENSE00003638089	57962012	57962176
ENSE00003644824	57992945	57993073
ENSE00003666599	57965725	57965827
ENSE00003681120	58010649	58010778
ENSE00003844819	57953429	57955269

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 98.91.

FANTOM5 (CAGE): breadth broad, TPM avg 11.6389 / max 342.5884, expressed in 560 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150203	9.7516	496
150204	1.1607	233
150207	0.2101	103
150208	0.1603	68
150200	0.0726	9
150220	0.0614	19
150206	0.0500	18
150205	0.0486	25
150199	0.0380	3
150216	0.0336	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	98.91	gold quality
decidua	UBERON:0002450	98.02	gold quality
sperm	CL:0000019	97.08	gold quality
adrenal tissue	UBERON:0018303	97.01	gold quality
male germ cell	CL:0000015	96.42	gold quality
seminal vesicle	UBERON:0000998	95.68	gold quality
secondary oocyte	CL:0000655	95.60	gold quality
right uterine tube	UBERON:0001302	95.38	gold quality
endometrium	UBERON:0001295	94.85	gold quality
parietal pleura	UBERON:0002400	94.62	gold quality
cauda epididymis	UBERON:0004360	94.57	gold quality
body of uterus	UBERON:0009853	93.65	gold quality
oocyte	CL:0000023	93.30	gold quality
uterus	UBERON:0000995	92.79	gold quality
myometrium	UBERON:0001296	92.68	gold quality
adult organism	UBERON:0007023	92.26	gold quality
endocervix	UBERON:0000458	92.19	gold quality
right atrium auricular region	UBERON:0006631	91.44	gold quality
left testis	UBERON:0004533	90.92	gold quality
right testis	UBERON:0004534	90.70	gold quality
testis	UBERON:0000473	90.66	gold quality
right lobe of liver	UBERON:0001114	90.62	gold quality
cardiac atrium	UBERON:0002081	90.33	gold quality
gall bladder	UBERON:0002110	89.88	gold quality
calcaneal tendon	UBERON:0003701	89.81	gold quality
prostate gland	UBERON:0002367	89.77	gold quality
pleura	UBERON:0000977	89.21	gold quality
ectocervix	UBERON:0012249	89.08	gold quality
metanephros cortex	UBERON:0010533	88.45	gold quality
metanephros	UBERON:0000081	88.19	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	4783.92
E-GEOD-131882	yes	3865.64
E-GEOD-124472	yes	851.31
E-MTAB-10287	yes	128.01
E-HCAD-10	yes	65.00
E-MTAB-6678	yes	27.81
E-ANND-3	yes	16.76
E-MTAB-7303	no	42.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3, HOXA13, HOXA1, IRF4, PBX1, PBX2, PKNOX1, SPI1, TAL1, WT1

miRNA regulators (miRDB)

96 targeting ALDH1A2, 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-5692A	100.00	74.40	6850
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514

Literature-anchored findings (GeneRIF, showing 31)

• polymorphisms in ALDH1A2 may influence the risk for lumbosacral myelomeningocele (PMID:16237707)
• Raldh2-/- knockout embryos exhibit defective morphogenesis of various forebrain derivatives, including the ventral diencephalon, the optic and telencephalic vesicles. (PMID:16368932)
• Gene duplication event that gave rise to Aldh1a1 and Aldh1a2 was more recent than the duplication event that gave rise to Aldh1a3. (PMID:19478994)
• The results of this study suggested a positive association between ALDH1A2 and schizophrenics in the Chinese population and support the retinoid hypothesis of schizophrenia. (PMID:19703508)
• our screen indicates that ALDH1A2 genetic variation is present in tetralogy of Fallot patients, suggesting a possible causal role for this gene in rare cases of human congenital heart disease (PMID:19886994)
• Individual variation in ALDH1A2/CRABP2 genes may account for subtle variations in retinoic acid-dependent human embryogenesis. (PMID:20308937)
• A human ALDH1A2 gene variant is associated with increased newborn kidney size and serum retinoic acid. (PMID:20375987)
• Aberrant methylation of ALDH1a2 gene is the main cause for gene transcriptional inactivation in human bladder cancer cell lines. 5-Aza-2’-deoxycitydine or trichostatin A treatment induces ALDH1a2 expression. (PMID:20450613)
• In vivo reduction of vitamin A levels results in an increase in astrocyte RALDH2 expression in the hippocampus. (PMID:22930583)
• ALDH1A2 protein was effective in AraC resistance. ALDH1A2 knock-down induced sensitivity to AraC treatment in K562AC cells. ALDH1A2 overexpressed K562S cells acquired the AraC resistance. Ara-C-resistant patients had increased ALDH1A2. (PMID:23507523)
• all three proteins (RDH10, RALDH2, and CRABP2) appeared to be required for ATRA production induced by activation of PPARgamma (PMID:23833249)
• DNA methylation at multiple CpG sites is associated with loss of control over alcohol drinking. (PMID:24236815)
• These findings suggest that ALDH1A2 is the enzyme involved in retinoic acid biosynthesis in human germ cells. (PMID:24524833)
• Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31. (PMID:24728293)
• At the transcript level, the cisplatin + DEAB-resistant cells showed upregulated mRNA expression levels for ALDH1A2, ALDH1A3 isozymes and CD44 indicating the involvement of these markers in conferring chemoresistance (PMID:24884875)
• Genetic association replicative and exploratory studies identify SNPs in ADA and MTR highly associated with isolated Neural tube defects (NTD)and SNP in ARID1A and ALDH1A2 associated with NTDs in whites and African Americans respectively. (PMID:25293959)
• ALDH1A2 is involved in the regulation of cancer stem cell properties in neuroblastoma. (PMID:25524880)
• the distribution of RALDH1, RALDH2, and RALDH3 in the postnatal eye was determined. (PMID:25793304)
• High expression of ALDH1A2 and ALDH1B1 mRNA was found to be significantly correlated to worser survival in all NSCLC patients. (PMID:26366059)
• a critical role of ALDH1A2-RAR signaling in the pathogenesis of head and neck cancer. (PMID:26634247)
• Data show that hRALDH2 is not inhibited by its oxidation product, all-trans-RA, suggesting the absence of a negative feedback regulatory loop. Expression of the Raldh2 gene is known to be regulated by RA itself, suggesting that the main regulation of the hRALDH2 activity level is transcriptional. (PMID:27001866)
• high transcription activities of ALDH1A2, ALDH1A3 and ALDH1L1 predicted worsen overall survival in gastric cancer patients (PMID:27015121)
• Study shows no evidence that genetic variants alter prostate cancer incidence, but show that SNPs in the ALDH1A2 gene affect prostate cancer mortality. (PMID:27643404)
• The authors findings indicate that the SNP rs4238326 in ALDH1A2 gene may potentially modify individual susceptibility to knee OA in the Chinese population. (PMID:28089900)
• The ALDH1A2 locus seems to increase the risk of hand osteoarthritis through decreased expression of ALDH1A2 in joint tissues, with the effect dependent on single-nucleotide polymorphism rs12915901. (PMID:29732726)
• ALDH1A2 and ALDH1A3 showed higher catalytic efficiency for all-trans-retinaldehyde. Magnesium inhibited ALDH1A1 and ALDH1A2, while it activated ALDH1A3. (PMID:31923393)
• Peanut protein acts as a TH2 adjuvant by inducing RALDH2 in human antigen-presenting cells. (PMID:33378690)
• The Presence and Potential Role of ALDH1A2 in the Glioblastoma Microenvironment. (PMID:34572134)
• An eQTL variant of ALDH1A2 is associated with Kashin-Beck disease in Chinese population. (PMID:35059888)
• ALDH1A2-related disorder: A new genetic syndrome due to alteration of the retinoic acid pathway. (PMID:36263470)
• A functional variant of ALDH1A2 is associated with hand osteoarthritis in the Chinese population. (PMID:38441233)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	aldh1a2	ENSDARG00000053493
mus_musculus	Aldh1a2	ENSMUSG00000013584
rattus_norvegicus	Aldh1a2	ENSRNOG00000055049
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), ALDH3B2 (ENSG00000132746), ALDH1L2 (ENSG00000136010), ALDH1B1 (ENSG00000137124), ALDH9A1 (ENSG00000143149), ALDH1L1 (ENSG00000144908), ALDH4A1 (ENSG00000159423), ALDH16A1 (ENSG00000161618), ALDH7A1 (ENSG00000164904), ALDH1A1 (ENSG00000165092), ALDH1A3 (ENSG00000184254)

Protein

Protein identifiers

Retinal dehydrogenase 2 — O94788 (reviewed: O94788)

Alternative names: Aldehyde dehydrogenase family 1 member A2, Retinaldehyde-specific dehydrogenase type 2

All UniProt accessions (7): O94788, A0A0G2JL97, E9PF31, H0YKL3, H0YMG7, H0YMT5, Q9UED3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the NAD-dependent oxidation of aldehyde substrates, such as all-trans-retinal and all-trans-13,14-dihydroretinal, to their corresponding carboxylic acids, all-trans-retinoate and all-trans-13,14-dihydroretinoate, respectively. Retinoate signaling is critical for the transcriptional control of many genes, for instance it is crucial for initiation of meiosis in both male and female. Recognizes retinal as substrate, both in its free form and when bound to cellular retinol-binding protein. Can metabolize octanal and decanal, but has only very low activity with benzaldehyde, acetaldehyde and propanal. Displays complete lack of activity with citral.

Subunit / interactions. Homotetramer.

Subcellular location. Cytoplasm.

Disease relevance. Diaphragmatic hernia 4, with cardiovascular defects (DIH4) [MIM:620025] An autosomal recessive form of congenital diaphragmatic hernia, a posterolateral defect of the diaphragm, generally located on the left side, that permits the herniation of abdominal viscera into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Cofactor metabolism; retinol metabolism.

Similarity. Belongs to the aldehyde dehydrogenase family.

Isoforms (4)

UniProt ID	Names	Canonical?
O94788-1	1	yes
O94788-2	2
O94788-3	3
O94788-4	4

RefSeq proteins (4): NP_001193826, NP_003879, NP_733797, NP_733798 (=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), 3 shown:

• retinal + NAD(+) + H2O = retinoate + NADH + 2 H(+) (RHEA:16177)
• all-trans-retinal + NAD(+) + H2O = all-trans-retinoate + NADH + 2 H(+) (RHEA:42080)
• all-trans-13,14-dihydroretinal + NAD(+) + H2O = all-trans-13,14-dihydroretinoate + NADH + 2 H(+) (RHEA:75119)

UniProt features (68 total): strand 24, helix 19, sequence variant 8, binding site 5, splice variant 3, active site 2, modified residue 2, turn 2, chain 1, sequence conflict 1, site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
9R6N	X-RAY DIFFRACTION	1.4
6ALJ	X-RAY DIFFRACTION	1.89
6B5G	X-RAY DIFFRACTION	2.2
6B5H	X-RAY DIFFRACTION	2.3
6B5I	X-RAY DIFFRACTION	2.6
9R3Z	X-RAY DIFFRACTION	2.8
4X2Q	X-RAY DIFFRACTION	2.94

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94788-F1	95.97	0.95

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): 286 (proton acceptor); 320 (nucleophile); 187 (transition state stabilizer)

Ligand- & substrate-binding residues (5): 184–186; 210–213; 264–266; 366–370; 417

Post-translational modifications (2): 351, 168

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5365859	RA biosynthesis pathway
R-HSA-162582	Signal Transduction
R-HSA-5362517	Signaling by Retinoic Acid
R-HSA-9006931	Signaling by Nuclear Receptors

MSigDB gene sets: 509 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, FXR_IR1_Q6, GOBP_HINDBRAIN_DEVELOPMENT, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_URETER_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, MYOGENIN_Q6, GOBP_RESPONSE_TO_ESTRADIOL, CCAWYNNGAAR_UNKNOWN, GOBP_PROTEIN_HOMOTETRAMERIZATION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID

GO Biological Process (47): blood vessel development (GO:0001568), somitogenesis (GO:0001756), kidney development (GO:0001822), liver development (GO:0001889), retinoic acid biosynthetic process (GO:0002138), heart morphogenesis (GO:0003007), aldehyde metabolic process (GO:0006081), vitamin A metabolic process (GO:0006776), midgut development (GO:0007494), cell population proliferation (GO:0008283), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), determination of bilateral symmetry (GO:0009855), proximal/distal pattern formation (GO:0009954), positive regulation of gene expression (GO:0010628), neural crest cell development (GO:0014032), morphogenesis of embryonic epithelium (GO:0016331), neural tube development (GO:0021915), pituitary gland development (GO:0021983), neuron differentiation (GO:0030182), lung development (GO:0030324), hindbrain development (GO:0030902), pancreas development (GO:0031016), embryonic camera-type eye development (GO:0031076), response to estradiol (GO:0032355), response to retinoic acid (GO:0032526), response to vitamin A (GO:0033189), response to cytokine (GO:0034097), embryonic forelimb morphogenesis (GO:0035115), ureter maturation (GO:0035799), retinol metabolic process (GO:0042572), retinoic acid metabolic process (GO:0042573), retinal metabolic process (GO:0042574), 9-cis-retinoic acid biosynthetic process (GO:0042904), positive regulation of apoptotic process (GO:0043065), retinoic acid receptor signaling pathway (GO:0048384), embryonic digestive tract development (GO:0048566), cardiac muscle tissue development (GO:0048738), protein homotetramerization (GO:0051289), face development (GO:0060324)

GO Molecular Function (6): retinal dehydrogenase (NAD+) activity (GO:0001758), 3-chloroallyl aldehyde dehydrogenase activity (GO:0004028), aldehyde dehydrogenase (NAD+) activity (GO:0004029), retinal binding (GO:0016918), 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 (3): cytoplasm (GO:0005737), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by Retinoic Acid	1
Signaling by Nuclear Receptors	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
chordate embryonic development	2
gland development	2
cell population proliferation	2
regulation of cell population proliferation	2
cytoplasm	2
vasculature development	1
anatomical structure development	1
anterior/posterior pattern specification	1
segmentation	1
anatomical structure formation involved in morphogenesis	1
somite development	1
animal organ development	1
renal system development	1
hepaticobiliary system development	1
diterpenoid biosynthetic process	1
retinoic acid metabolic process	1
monocarboxylic acid biosynthetic process	1
heart development	1
animal organ morphogenesis	1
metabolic process	1
retinoid metabolic process	1
digestive tract development	1
cellular process	1
positive regulation of cellular process	1
negative regulation of cellular process	1
specification of symmetry	1
regionalization	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
neural crest cell differentiation	1
stem cell development	1
morphogenesis of an epithelium	1
embryonic morphogenesis	1
nervous system development	1
tube development	1
epithelium development	1
diencephalon development	1
endocrine system development	1

Protein interactions and networks

STRING

4206 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALDH1A2	CYP26A1	O43174	905
ALDH1A2	CYP26B1	Q9NR63	876
ALDH1A2	CYP26C1	Q6V0L0	825
ALDH1A2	RDH10	Q8IZV5	719
ALDH1A2	RARS1	P54136	668
ALDH1A2	TBX18	O95935	665
ALDH1A2	RARA	P10276	623
ALDH1A2	RARB	P10826	622
ALDH1A2	RARG	P13631	620
ALDH1A2	STRA6	Q9BX79	601
ALDH1A2	CRABP2	P29373	581
ALDH1A2	ITGAE	P38570	577
ALDH1A2	RBP1	P09455	576
ALDH1A2	TCF21	O43680	576
ALDH1A2	FOXP3	Q9BZS1	572

IntAct

26 interactions, top by confidence:

A	B	Type	Score
PRKAA1	PRKAB2	psi-mi:“MI:0914”(association)	0.950
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
WASHC3	WASH3P	psi-mi:“MI:0914”(association)	0.530
ALDH1A1	ALDH1A2	psi-mi:“MI:0915”(physical association)	0.400
ZNF69	ALDH1A2	psi-mi:“MI:0915”(physical association)	0.400
SH3BGRL3	ALDH1A2	psi-mi:“MI:0915”(physical association)	0.400
ANKRD33	ALDH1A2	psi-mi:“MI:0915”(physical association)	0.400
CA4	ALDH1A2	psi-mi:“MI:0915”(physical association)	0.400
OR3A1	ALDH1A2	psi-mi:“MI:0915”(physical association)	0.400
ALDH1A2	UBE2D4	psi-mi:“MI:0915”(physical association)	0.370
NA	IPO5	psi-mi:“MI:0914”(association)	0.350
	DENND11	psi-mi:“MI:0914”(association)	0.350
ALDH2	ALDH1A2	psi-mi:“MI:0914”(association)	0.350
IDS	RTCA	psi-mi:“MI:0914”(association)	0.350
ERLEC1	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
GAL	GNPAT	psi-mi:“MI:0914”(association)	0.350
SFXN2	RBFOX2	psi-mi:“MI:0914”(association)	0.350
KPTN	ALDH1A2	psi-mi:“MI:0914”(association)	0.350
BOC	ALDH1A2	psi-mi:“MI:0914”(association)	0.350
CHMP6	ALDH1A2	psi-mi:“MI:0914”(association)	0.350
METTL6	ALDH1A2	psi-mi:“MI:0914”(association)	0.350
AKTIP	ALDH1A2	psi-mi:“MI:0914”(association)	0.350
NANS	ALDH1A2	psi-mi:“MI:0914”(association)	0.350
CANX	PDLIM1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (57): ALDH1A2 (Affinity Capture-MS), ALDH1A2 (Proximity Label-MS), ALDH1A2 (Affinity Capture-MS), ALDH1A2 (Affinity Capture-MS), ALDH1A2 (Proximity Label-MS), ALDH1A2 (Proximity Label-MS), ALDH1A2 (Proximity Label-MS), ALDH1A2 (Proximity Label-MS), ALDH1A2 (Affinity Capture-MS), ALDH1A2 (Affinity Capture-MS), ALDH1A2 (Proximity Label-MS), ALDH1A2 (Two-hybrid), ALDH1A2 (Affinity Capture-Western), ALDH1A2 (Biochemical Activity), ALDH1A2 (Reconstituted Complex)

ESM2 similar proteins: A0A0E3T3B5, A0A0E3T552, A0A2I7G3B0, A0A5C1REZ4, A7ZI51, B0CKN3, B1J0W5, B3VMC0, B6ECN9, B7M2V6, B7MCD1, B7N8L4, B7NK50, B8M9K4, C0P9J6, C6KEM4, G5DDC2, H8ZPX2, O04895, O06837, O14293, O24174, O59808, O74187, O93344, O94788, P13601, P17202, P28237, P42269, P42757, P47895, Q0TKW0, Q28399, Q29490, Q32FQ5, Q40024, Q56R04, Q62148, Q63639

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

3 interactions.

A	Effect	B	Mechanism
ALDH1A2	“down-regulates quantity”	retinal	“chemical modification”
ALDH1A2	“up-regulates quantity”	“all-trans-retinoic acid”	“chemical modification”
UBE3A	“down-regulates quantity by destabilization”	ALDH1A2	ubiquitination

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	37
Likely benign	8
Benign	34

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1703736	NM_003888.4(ALDH1A2):c.544C>A (p.Gln182Lys)	Pathogenic
1703737	NM_003888.4(ALDH1A2):c.1382C>A (p.Ser461Tyr)	Pathogenic
1703738	NM_003888.4(ALDH1A2):c.1147G>A (p.Ala383Thr)	Pathogenic
1703739	NM_003888.4(ALDH1A2):c.1040G>A (p.Arg347His)	Pathogenic
3391924	GRCh37/hg19 15q21.3(chr15:54281939-58773686)x1	Pathogenic

SpliceAI

3385 predictions. Top by Δscore:

Variant	Effect	Δscore
15:57960768:A:AC	donor_gain	1.0000
15:57960769:C:CC	donor_gain	1.0000
15:57960769:CATTT:C	donor_gain	1.0000
15:57961132:CTTA:C	donor_loss	1.0000
15:57961134:TACCA:T	donor_loss	1.0000
15:57961135:A:AC	donor_gain	1.0000
15:57961136:C:CC	donor_gain	1.0000
15:57961136:C:T	donor_loss	1.0000
15:57961136:CCAAA:C	donor_gain	1.0000
15:57961290:AAGAT:A	acceptor_gain	1.0000
15:57961291:AGAT:A	acceptor_gain	1.0000
15:57961292:GAT:G	acceptor_gain	1.0000
15:57961293:AT:A	acceptor_gain	1.0000
15:57961294:TC:T	acceptor_loss	1.0000
15:57961295:C:CC	acceptor_gain	1.0000
15:57961295:C:CG	acceptor_loss	1.0000
15:57962007:GATAC:G	donor_loss	1.0000
15:57962008:ATAC:A	donor_loss	1.0000
15:57962009:TACCT:T	donor_loss	1.0000
15:57962010:AC:A	donor_loss	1.0000
15:57962014:C:A	donor_gain	1.0000
15:57962016:T:TA	donor_gain	1.0000
15:57962172:TCAAT:T	acceptor_gain	1.0000
15:57962173:CAAT:C	acceptor_gain	1.0000
15:57962173:CAATC:C	acceptor_gain	1.0000
15:57962174:AAT:A	acceptor_gain	1.0000
15:57962174:AATCT:A	acceptor_loss	1.0000
15:57962177:C:CC	acceptor_gain	1.0000
15:57962177:CT:C	acceptor_loss	1.0000
15:57962178:T:A	acceptor_loss	1.0000

AlphaMissense

3409 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:57960785:C:T	G490E	0.999
15:57961147:C:A	G467W	0.999
15:57993068:G:C	N187K	0.999
15:57993068:G:T	N187K	0.999
15:57960800:C:T	G485E	0.998
15:57960803:C:T	G484E	0.998
15:57961146:C:A	G467V	0.998
15:57961146:C:T	G467E	0.998
15:57961200:A:T	V449D	0.998
15:57961212:A:G	L445P	0.998
15:57961262:A:C	F428L	0.998
15:57961262:A:T	F428L	0.998
15:57961264:A:G	F428L	0.998
15:57961281:A:T	V422D	0.998
15:57961289:A:C	F419L	0.998
15:57961289:A:T	F419L	0.998
15:57961291:A:G	F419L	0.998
15:57964049:C:G	A308P	0.998
15:57965766:A:G	L287P	0.998
15:57992716:C:A	G263W	0.998
15:57993065:G:C	F188L	0.998
15:57993065:G:T	F188L	0.998
15:57993067:A:G	F188L	0.998
15:57960785:C:A	G490V	0.997
15:57960805:A:C	F483L	0.997
15:57960805:A:T	F483L	0.997
15:57960807:A:G	F483L	0.997
15:57960839:T:A	N472I	0.997
15:57961138:A:G	W470R	0.997
15:57961138:A:T	W470R	0.997

dbSNP variants (sampled 300 via entrez): RS1000050330 (15:57990472 C>G,T), RS1000061772 (15:58065235 G>A,C), RS1000073619 (15:58011949 G>A,T), RS1000082056 (15:57975521 G>C,T), RS1000151899 (15:58027484 C>T), RS1000157438 (15:57961137 C>A,G,T), RS1000265728 (15:58025170 A>T), RS1000279107 (15:57987667 T>G), RS1000382251 (15:58066470 C>A), RS1000384773 (15:58062565 C>A), RS1000437020 (15:58062280 A>C), RS1000493582 (15:58029270 T>C), RS1000506185 (15:58016228 T>C), RS1000513784 (15:57983163 G>T), RS1000538801 (15:58015990 A>G)

Disease associations

OMIM: gene MIM:603687 | disease phenotypes: MIM:620025

GenCC curated gene-disease

Disease	Classification	Inheritance
diaphragmatic hernia 4, with cardiovascular defects	Strong	Autosomal recessive

Mondo (1): diaphragmatic hernia 4, with cardiovascular defects (MONDO:0859571)

Orphanet (0):

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000256	Macrocephaly
HP:0000331	Short chin
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000414	Bulbous nose
HP:0000465	Webbed neck
HP:0000494	Downslanted palpebral fissures
HP:0000609	Optic nerve hypoplasia
HP:0000878	11 pairs of ribs
HP:0001561	Polyhydramnios
HP:0001629	Ventricular septal defect
HP:0001762	Talipes equinovarus
HP:0002089	Pulmonary hypoplasia
HP:0002092	Pulmonary arterial hypertension
HP:0002240	Hepatomegaly
HP:0002616	Aortic root aneurysm
HP:0002643	Neonatal respiratory distress
HP:0002719	Recurrent infections
HP:0003417	Coronal cleft vertebrae
HP:0004209	Clinodactyly of the 5th finger
HP:0004691	2-3 toe syndactyly
HP:0004971	Pulmonary artery hypoplasia
HP:0006101	Finger syndactyly
HP:0009110	Diaphragmatic eventration
HP:0009112	Aplasia of the left hemidiaphragm
HP:0011604	Aortopulmonary window
HP:0030674	Antenatal onset
HP:0031834	Aortopulmonary collateral arteries

GWAS associations

56 associations (top):

Study	Trait	p-value
GCST000447_2	Hypertension	3.000000e-06
GCST002410_1	Osteoarthritis (hand, severe)	1.000000e-11
GCST002875_16	Diisocyanate-induced asthma	1.000000e-06
GCST002875_20	Diisocyanate-induced asthma	1.000000e-06
GCST002987_11	Stroke	4.000000e-08
GCST002987_25	Stroke	4.000000e-08
GCST002988_7	Ischemic stroke	5.000000e-07
GCST002988_9	Ischemic stroke	5.000000e-07
GCST003738_1	Barrett’s esophagus	3.000000e-10
GCST003740_2	Barrett’s esophagus or Esophageal adenocarcinoma	5.000000e-10
GCST004207_7	HDL cholesterol	3.000000e-25
GCST004746_44	Small cell lung carcinoma	4.000000e-06
GCST005039_2	Uncontrolled blood pressure in combination therapy (beta blocker and thiazide diuretic)	9.000000e-08
GCST006611_79	HDL cholesterol	6.000000e-216
GCST006612_110	LDL cholesterol	4.000000e-09
GCST006614_89	Total cholesterol levels	4.000000e-78
GCST007931_47	Medication use (HMG CoA reductase inhibitors)	8.000000e-10
GCST007931_68	Medication use (HMG CoA reductase inhibitors)	4.000000e-08
GCST008163_625	Height	9.000000e-06
GCST009367_54	HDL cholesterol levels x short total sleep time interaction (2df test)	4.000000e-09
GCST009367_55	HDL cholesterol levels x short total sleep time interaction (2df test)	1.000000e-19
GCST009367_56	HDL cholesterol levels x short total sleep time interaction (2df test)	1.000000e-10
GCST009367_57	HDL cholesterol levels x short total sleep time interaction (2df test)	2.000000e-83
GCST009367_58	HDL cholesterol levels x short total sleep time interaction (2df test)	4.000000e-13
GCST009367_59	HDL cholesterol levels x short total sleep time interaction (2df test)	3.000000e-83
GCST009656_2	Low HDL-cholesterol levels	7.000000e-06
GCST009661_14	Low HDL-cholesterol levels	2.000000e-08
GCST010060_2	Cholesterol	2.000000e-18
GCST010173_41	Triglyceride levels	5.000000e-45
GCST010204_98	Low density lipoprotein cholesterol levels	2.000000e-30

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007766	response to beta blocker
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0004530	triglyceride measurement
EFO:0004346	neuroimaging measurement
EFO:0006925	lipoprotein A measurement
EFO:0004842	eosinophil count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004587	lymphocyte count
EFO:0004305	erythrocyte count
EFO:0006941	grip strength measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3112384 (SINGLE PROTEIN), CHEMBL3542434 (PROTEIN FAMILY)

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items; also 2 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
ALDH1A2 Underexpression	Tretinoin	Head And Neck Squamous Cell Carcinoma	Sensitivity/Response	CIViC D	EID1115

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12903202	Efficacy	3	Bisphosphonates	Osteonecrosis
rs261316	Efficacy	3	atenolol;hydrochlorothiazide	Hypertension

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12903202	ALDH1A2	3	0.00	1	Bisphosphonates
rs12915901	ALDH1A2		0.00	0

ChEMBL bioactivities

79 potent at pChembl≥5 of 84 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.68	IC50	21	nM	CHEMBL4849586
7.40	IC50	40	nM	CHEMBL4876602
7.25	Ki	56	nM	CHEMBL3276621
7.24	IC50	58	nM	CHEMBL4846203
7.20	IC50	63	nM	CHEMBL4875157
7.19	IC50	65	nM	CHEMBL4090473
7.19	Ki	64.35	nM	CHEMBL4286209
7.19	IC50	65	nM	CHEMBL4847114
7.16	IC50	69	nM	CHEMBL1562069
7.10	IC50	80	nM	CHEMBL4859904
7.05	IC50	89	nM	CHEMBL4855442
7.00	IC50	100	nM	CHEMBL4848831
7.00	IC50	100	nM	CHEMBL5283146
7.00	IC50	100	nM	CHEMBL5269320
6.97	IC50	108	nM	CHEMBL4846491
6.96	IC50	110	nM	CHEMBL4862833
6.96	IC50	110	nM	CHEMBL4848258
6.95	IC50	112	nM	CHEMBL4861872
6.89	IC50	130	nM	CHEMBL1349972
6.87	IC50	136	nM	CHEMBL4874309
6.82	IC50	150	nM	CHEMBL4213331
6.77	IC50	170	nM	CHEMBL4873090
6.75	IC50	179	nM	CHEMBL4876076
6.72	IC50	191.3	nM	CHEMBL4286209
6.67	IC50	216	nM	CHEMBL4867380
6.64	IC50	230	nM	CHEMBL4216790
6.62	IC50	240	nM	CHEMBL4873315
6.60	IC50	250	nM	CHEMBL4210115
6.57	IC50	270	nM	CHEMBL4868666
6.52	IC50	300	nM	CHEMBL4099822
6.52	IC50	300	nM	CHEMBL4863668
6.48	IC50	330	nM	CHEMBL4072941
6.47	IC50	340	nM	CHEMBL4214509
6.42	IC50	380	nM	CHEMBL4849624
6.40	IC50	400	nM	CHEMBL4860590
6.38	Ki	420	nM	CHEMBL3276621
6.36	IC50	440	nM	CHEMBL4848961
6.32	IC50	480	nM	CHEMBL4217452
6.25	IC50	560	nM	CHEMBL4210318
6.22	IC50	600	nM	CHEMBL4866017
6.17	IC50	670	nM	CHEMBL4217294
6.14	IC50	720	nM	CHEMBL4209261
6.12	IC50	760	nM	CHEMBL4064364
6.10	IC50	800	nM	CHEMBL4877915
6.09	IC50	810	nM	CHEMBL4865571
6.05	IC50	900	nM	CHEMBL4213859
6.05	IC50	890	nM	CHEMBL4871374
6.04	Ki	920	nM	CHEMBL4642789
6.00	IC50	1000	nM	CHEMBL5271934
6.00	IC50	1000	nM	CHEMBL5274968

PubChem BioAssay actives

79 with measured affinity, of 229 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
2-(oxetan-3-yl)-5-phenyl-6-(1-pyridin-2-ylethylsulfanyl)pyrazolo[3,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.0210	uM
1-methyl-5-phenyl-6-[(1R)-1-phenylethyl]sulfanylpyrazolo[5,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.0400	uM
2,2-dichloro-N-[8-[(2,2-dichloroacetyl)amino]octyl]acetamide	1387302: Inhibition of human ALDH1A2	ki	0.0560	uM
2-(oxetan-3-yl)-5-phenyl-6-(1-pyridin-3-ylethylsulfanyl)pyrazolo[3,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.0580	uM
1-methyl-5-phenyl-6-(1-pyridin-2-ylethylsulfanyl)pyrazolo[5,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.0630	uM
(3E,5E,7E,9E)-1,1-dichloro-4,8-dimethyl-10-(2,6,6-trimethylcyclohexen-1-yl)deca-3,5,7,9-tetraen-2-one	1418965: Inhibition of N-terminal His6-tagged recombinant human RALDH2 using RAL as substrate measured after 30 mins in presence of NADH by Morrison’s plot analysis	ki	0.0644	uM
2-(oxetan-3-yl)-5-phenyl-6-(1-phenylethylsulfanyl)pyrazolo[3,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.0650	uM
9,10-dimethyl-1,2,3,4-tetrahydro-[1]benzofuro[6,5-c]isochromen-5-one	1441743: Inhibition of full length recombinant human ALDH1A2 expressed in Escherichia coli BL21(DE3) assessed as reduction in dehydrogenase activity by measuring NAD(P)H level preincubated for 2 mins followed by addition of propionaldehyde as substrate in presence of NAD+ by spectrophotometric method	ic50	0.0650	uM
2,3-dimethyl-5-propylfuro[3,2-g]chromen-7-one	1441743: Inhibition of full length recombinant human ALDH1A2 expressed in Escherichia coli BL21(DE3) assessed as reduction in dehydrogenase activity by measuring NAD(P)H level preincubated for 2 mins followed by addition of propionaldehyde as substrate in presence of NAD+ by spectrophotometric method	ic50	0.0690	uM
2-(oxetan-3-ylmethyl)-5-phenyl-6-(1-phenylethylsulfanyl)pyrazolo[3,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.0800	uM
1-methyl-5-phenyl-6-(1-pyridin-3-ylethylsulfanyl)pyrazolo[5,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.0890	uM
6-[1-(3-hydroxyphenyl)ethylsulfanyl]-1-methyl-5-phenylpyrazolo[5,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.1000	uM
6-[2-[2-(3-fluorophenyl)pyrrolidin-1-yl]ethoxy]-3,4-dihydro-1H-quinolin-2-one	1923283: Inhibition of full length human ALDH1A2 using propionaldehyde as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of NAD by luminescence microplate reader analysis	ic50	0.1000	uM
6-[2-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]ethoxy]-3,4-dihydro-1H-quinolin-2-one	1923283: Inhibition of full length human ALDH1A2 using propionaldehyde as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of NAD by luminescence microplate reader analysis	ic50	0.1000	uM
6-[1-(3-methoxyphenyl)ethylsulfanyl]-1-methyl-5-phenylpyrazolo[5,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.1080	uM
1-methyl-5-phenyl-6-(1-phenylethylsulfanyl)pyrazolo[5,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.1100	uM
6-[1-(3-fluorophenyl)ethylsulfanyl]-1-methyl-5-phenylpyrazolo[5,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.1100	uM
2-(3-methyloxetan-3-yl)-5-phenyl-6-(1-phenylethylsulfanyl)pyrazolo[3,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.1120	uM
13,14-dimethyl-8,12-dioxatetracyclo[7.7.0.02,6.011,15]hexadeca-1(9),2(6),10,13,15-pentaen-7-one	1441743: Inhibition of full length recombinant human ALDH1A2 expressed in Escherichia coli BL21(DE3) assessed as reduction in dehydrogenase activity by measuring NAD(P)H level preincubated for 2 mins followed by addition of propionaldehyde as substrate in presence of NAD+ by spectrophotometric method	ic50	0.1300	uM
6-[1-(2-methoxyphenyl)ethylsulfanyl]-1-methyl-5-phenylpyrazolo[5,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.1360	uM
6-[(3-fluorophenyl)methylsulfanyl]-1-methyl-5-phenylpyrazolo[5,4-d]pyrimidin-4-one	1387318: Inhibition of human recombinant ALDH1A2 assessed as reduction in of NAD(P)H formation incubated for 2 mins by spectrophotometry	ic50	0.1500	uM
3-methyl-8,11-diphenyl-10-thia-3,4,8-triazatricyclo[7.3.0.02,6]dodeca-1(9),2(6),4-triene-7,12-dione	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.1700	uM
1-methyl-5-phenyl-6-(1-phenylpropylsulfanyl)pyrazolo[5,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.1790	uM
5-[4-(2-hydroxyethyl)phenyl]-1-methyl-6-(1-phenylethylsulfanyl)pyrazolo[5,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.2160	uM
6-[(3-fluorophenyl)methylsulfanyl]-1-(oxetan-3-yl)-5-phenylpyrazolo[5,4-d]pyrimidin-4-one	1387318: Inhibition of human recombinant ALDH1A2 assessed as reduction in of NAD(P)H formation incubated for 2 mins by spectrophotometry	ic50	0.2300	uM
6-[(3-fluorophenyl)methylsulfanyl]-1-methyl-5-phenylpyrazolo[4,5-c]pyridin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.2400	uM
6-[(3-fluorophenyl)methylsulfanyl]-2-(oxetan-3-yl)-5-phenylpyrazolo[3,4-d]pyrimidin-4-one	1387318: Inhibition of human recombinant ALDH1A2 assessed as reduction in of NAD(P)H formation incubated for 2 mins by spectrophotometry	ic50	0.2500	uM
3-methyl-8,11-diphenyl-10-thia-3,4,8-triazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,12-tetraen-7-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.2700	uM
1-methyl-6-(2-methyl-1-phenylpropyl)sulfanyl-5-phenylpyrazolo[5,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.3000	uM
2,3,5-trimethyl-6-propylfuro[3,2-g]chromen-7-one	1441743: Inhibition of full length recombinant human ALDH1A2 expressed in Escherichia coli BL21(DE3) assessed as reduction in dehydrogenase activity by measuring NAD(P)H level preincubated for 2 mins followed by addition of propionaldehyde as substrate in presence of NAD+ by spectrophotometric method	ic50	0.3000	uM
2,3,5,6-tetramethylfuro[3,2-g]chromen-7-one	1441743: Inhibition of full length recombinant human ALDH1A2 expressed in Escherichia coli BL21(DE3) assessed as reduction in dehydrogenase activity by measuring NAD(P)H level preincubated for 2 mins followed by addition of propionaldehyde as substrate in presence of NAD+ by spectrophotometric method	ic50	0.3300	uM
6-[(3-fluorophenyl)methylsulfanyl]-2-methyl-5-phenylpyrazolo[3,4-d]pyrimidin-4-one	1387318: Inhibition of human recombinant ALDH1A2 assessed as reduction in of NAD(P)H formation incubated for 2 mins by spectrophotometry	ic50	0.3400	uM
1-methyl-5-phenyl-6-(1-pyrimidin-5-ylethylsulfanyl)pyrazolo[5,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.3800	uM
3-methyl-8,11-diphenyl-10-thia-3,4,8-triazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4-triene-7,13-dione	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.4000	uM
6-[(E)-2-(3-fluorophenyl)ethenyl]-1-methyl-5-phenylpyrazolo[5,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.4400	uM
6-[(3-fluorophenyl)methylsulfanyl]-2-(oxetan-3-ylmethyl)-5-phenylpyrazolo[3,4-d]pyrimidin-4-one	1387318: Inhibition of human recombinant ALDH1A2 assessed as reduction in of NAD(P)H formation incubated for 2 mins by spectrophotometry	ic50	0.4800	uM
5-(3-chlorophenyl)-6-[(3-fluorophenyl)methylsulfanyl]-1-methylpyrazolo[5,4-d]pyrimidin-4-one	1387318: Inhibition of human recombinant ALDH1A2 assessed as reduction in of NAD(P)H formation incubated for 2 mins by spectrophotometry	ic50	0.5600	uM
5-[4-(hydroxymethyl)phenyl]-1-methyl-6-(1-phenylethylsulfanyl)pyrazolo[5,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.6000	uM
6-[(3-fluorophenyl)methylsulfanyl]-5-phenyl-1H-pyrazolo[5,4-d]pyrimidin-4-one	1387318: Inhibition of human recombinant ALDH1A2 assessed as reduction in of NAD(P)H formation incubated for 2 mins by spectrophotometry	ic50	0.6700	uM
5-benzyl-6-[(3-fluorophenyl)methylsulfanyl]-1-methylpyrazolo[5,4-d]pyrimidin-4-one	1387318: Inhibition of human recombinant ALDH1A2 assessed as reduction in of NAD(P)H formation incubated for 2 mins by spectrophotometry	ic50	0.7200	uM
3,5-dimethyl-6-propylfuro[3,2-g]chromen-7-one	1441743: Inhibition of full length recombinant human ALDH1A2 expressed in Escherichia coli BL21(DE3) assessed as reduction in dehydrogenase activity by measuring NAD(P)H level preincubated for 2 mins followed by addition of propionaldehyde as substrate in presence of NAD+ by spectrophotometric method	ic50	0.7600	uM
5-(4-ethynylphenyl)-1-methyl-6-(1-phenylethylsulfanyl)pyrazolo[5,4-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.8000	uM
2-[(3-fluorophenyl)methylsulfanyl]-7-methyl-3-phenylpyrrolo[2,3-d]pyrimidin-4-one	1752914: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery	ic50	0.8100	uM
[4-[[1-[(3-chlorophenyl)methyl]benzimidazol-2-yl]methyl]piperazin-1-yl]-cyclopropylmethanone	1766109: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometry	ic50	0.8900	uM
6-[(3-fluorophenyl)methylsulfanyl]-1-methyl-5-(2-phenylethyl)pyrazolo[5,4-d]pyrimidin-4-one	1387318: Inhibition of human recombinant ALDH1A2 assessed as reduction in of NAD(P)H formation incubated for 2 mins by spectrophotometry	ic50	0.9000	uM
methyl 4-(2-phenylimidazo[1,2-a]pyridin-8-yl)benzoate	1649843: Competitive inhibition of human recombinant ALDH1A2 pre-incubated for 5 mins before acetaldehyde addition by continuous spectrometric assay relative to control	ki	0.9200	uM
2-(dimethylamino)-4-(3-fluorophenyl)-N-(2-oxo-3,4-dihydro-1H-quinolin-6-yl)-1,3-thiazole-5-carboxamide	1923283: Inhibition of full length human ALDH1A2 using propionaldehyde as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of NAD by luminescence microplate reader analysis	ic50	1.0000	uM
4-(3-fluorophenyl)-N-(2-oxo-3,4-dihydro-1H-quinolin-6-yl)-1,3-thiazole-5-carboxamide	1923283: Inhibition of full length human ALDH1A2 using propionaldehyde as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of NAD by luminescence microplate reader analysis	ic50	1.0000	uM
4-(2-fluorophenyl)-N-(2-oxo-3,4-dihydro-1H-quinolin-6-yl)-1,3-thiazole-5-carboxamide	1923283: Inhibition of full length human ALDH1A2 using propionaldehyde as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of NAD by luminescence microplate reader analysis	ic50	1.0000	uM
5-(4-chlorophenyl)-6-[(3-fluorophenyl)methylsulfanyl]-1-methylpyrazolo[5,4-d]pyrimidin-4-one	1387318: Inhibition of human recombinant ALDH1A2 assessed as reduction in of NAD(P)H formation incubated for 2 mins by spectrophotometry	ic50	1.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects reaction, increases expression, affects cotreatment, decreases expression, increases methylation	8
Tretinoin	decreases expression, increases chemical synthesis, affects cotreatment, increases expression	3
N,N’-bis(dichloroacetyl)-1,8-octamethylenediamine	decreases activity	2
trichostatin A	decreases expression	2
entinostat	affects cotreatment, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Doxorubicin	decreases response to substance, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	increases expression, decreases expression	2
bisphenol F	increases expression	1
sotorasib	affects cotreatment, increases expression	1
daidzein	affects cotreatment, affects expression	1
methylmercuric chloride	increases expression	1
bisphenol A	increases methylation, decreases methylation, affects cotreatment	1
molinate	decreases activity	1
perfosfamide	decreases response to substance	1
tributyltin	decreases activity	1
ethyl-p-hydroxybenzoate	decreases expression	1
triphenyltin chloride	decreases activity	1
tris(2-butoxyethyl) phosphate	affects expression	1
daidzin	affects cotreatment, affects expression	1
arsenite	decreases expression	1
decamethrin	increases activity	1
enilconazole	increases activity	1
sodium arsenite	affects methylation	1
cobaltous chloride	decreases expression	1
doxylamine succinate	decreases expression	1
procymidone	decreases activity	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression, affects cotreatment	1

ChEMBL screening assays

32 unique, capped per target: 32 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3118129	Binding	Inhibition of human ALDH1A2 using propionaldehyde as substrate up to 100 uM preincubated for 1 min followed by substrate addition by spectrophotometric analysis	Selective ALDH3A1 inhibition by benzimidazole analogues increase mafosfamide sensitivity in cancer cells. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D2I1	Abcam Raji ALDH1A2 KO	Cancer cell line	Male
CVCL_UQ12	Abcam Jurkat ALDH1A2 KO	Cancer cell line	Male
CVCL_WQ96	Abcam K-562 ALDH1A2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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