ALDH3A1

Summary

ALDH3A1 (aldehyde dehydrogenase 3 family member A1, HGNC:405) is a protein-coding gene on chromosome 17p11.2, encoding Aldehyde dehydrogenase, dimeric NADP-preferring (P30838). ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde.

Aldehyde dehydrogenases oxidize various aldehydes to the corresponding acids. They are involved in the detoxification of alcohol-derived acetaldehyde and in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation. The enzyme encoded by this gene forms a cytoplasmic homodimer that preferentially oxidizes aromatic and medium-chain (6 carbons or more) saturated and unsaturated aldehyde substrates. It is thought to promote resistance to UV and 4-hydroxy-2-nonenal-induced oxidative damage in the cornea. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 218 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 63 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_000691

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:405
Approved symbol	ALDH3A1
Name	aldehyde dehydrogenase 3 family member A1
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000108602
Ensembl biotype	protein_coding
Entrez	218

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 19 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000225740, ENST00000395555, ENST00000426645, ENST00000439102, ENST00000444455, ENST00000457500, ENST00000468746, ENST00000479677, ENST00000485231, ENST00000485472, ENST00000487650, ENST00000494157, ENST00000570414, ENST00000573368, ENST00000574162, ENST00000575103, ENST00000575860, ENST00000905961, ENST00000905962, ENST00000905963, ENST00000905964, ENST00000905965, ENST00000905966, ENST00000905967, ENST00000905968, ENST00000946889

RefSeq mRNA: 4 — MANE Select: NM_000691 NM_000691, NM_001135167, NM_001135168, NM_001330150

CCDS: CCDS11212, CCDS82090

Canonical transcript exons

ENST00000225740 — 11 exons

Exon	Start	End
ENSE00001827868	19748259	19748298
ENSE00002734215	19744968	19745134
ENSE00003498318	19738996	19739095
ENSE00003520876	19740336	19740477
ENSE00003542414	19742545	19742630
ENSE00003615796	19742004	19742212
ENSE00003624726	19738323	19738453
ENSE00003784936	19739508	19739674
ENSE00003787091	19743232	19743463
ENSE00003787114	19741093	19741210
ENSE00003846695	19737989	19738235

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 99.53.

FANTOM5 (CAGE): breadth broad, TPM avg 5.7469 / max 2341.2054, expressed in 294 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164884	4.8105	167
164886	0.3329	94
164885	0.2655	65
164881	0.0970	31
164887	0.0859	42
164878	0.0652	27
164880	0.0485	23
164882	0.0281	7
164879	0.0133	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nasal cavity epithelium	UBERON:0005384	99.53	gold quality
trachea	UBERON:0003126	99.45	gold quality
lower esophagus mucosa	UBERON:0035834	99.43	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.26	gold quality
pharyngeal mucosa	UBERON:0000355	98.97	gold quality
nasal cavity mucosa	UBERON:0001826	98.95	gold quality
esophagus squamous epithelium	UBERON:0006920	98.18	gold quality
esophagus mucosa	UBERON:0002469	98.11	gold quality
gingiva	UBERON:0001828	97.75	gold quality
gingival epithelium	UBERON:0001949	97.62	gold quality
epithelium of esophagus	UBERON:0001976	97.47	gold quality
oral cavity	UBERON:0000167	97.32	gold quality
tongue squamous epithelium	UBERON:0006919	96.46	gold quality
bronchus	UBERON:0002185	96.34	gold quality
mucosa of stomach	UBERON:0001199	96.28	gold quality
epithelium of bronchus	UBERON:0002031	96.22	gold quality
bronchial epithelial cell	CL:0002328	95.90	gold quality
squamous epithelium	UBERON:0006914	94.36	gold quality
body of tongue	UBERON:0011876	94.28	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.89	gold quality
epithelium of nasopharynx	UBERON:0001951	91.73	gold quality
tongue	UBERON:0001723	91.57	gold quality
skin of abdomen	UBERON:0001416	89.70	gold quality
superior surface of tongue	UBERON:0007371	89.16	gold quality
pylorus	UBERON:0001166	88.86	gold quality
body of stomach	UBERON:0001161	88.74	gold quality
skin of leg	UBERON:0001511	88.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.70	gold quality
zone of skin	UBERON:0000014	87.19	gold quality
palpebral conjunctiva	UBERON:0001812	86.96	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	220.03
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, ARNT, EP300, HNF1A, HNF4A, PAX6, POU2F1, SP1, TCF3, TP53

miRNA regulators (miRDB)

24 targeting ALDH3A1, 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-4481	100.00	66.42	1669
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-628-5P	98.36	67.74	844
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-890	97.47	68.67	982
HSA-MIR-6773-5P	97.04	64.30	595
HSA-MIR-601	95.98	67.59	421

Literature-anchored findings (GeneRIF, showing 30)

• ADH3*1 allele associated with high ADH activity and acetyaldehyde-DNA adducts in lung; may be a risk factor for lung cancer (PMID:12367788)
• ALDH3A1 is a regulatory element of the cellular defense system that protects corneal epithelium against UV-induced oxidative damage (PMID:12706498)
• Enzyme activity and localization of ALDH3A1 in the cornea. (PMID:12943535)
• ALDH3A1 may protect corneal epithelial cells against oxidative damage not only through its metabolic function but also by prolonging the cell cycle (PMID:15905174)
• In most cases, ALDH3A1 activity in tumor and bordering tissues was higher than in a control group (PMID:18536178)
• These kinetic properties ensure that ALDHs, and particularly ALDH2, can complete the ADH-mediated detoxification. (PMID:18621017)
• specific down regulation of ALDH1A1 and ALDH3A1 in Lenti 1+3 cells and in comparison to 12 other ALDH genes detected (PMID:19025616)
• the mechanism of salivary ALDH3A1 inactivation must be related to free radical activity, presumably in the salivary gland, but it is not simply correlated with antioxidatn capacity of saliva (PMID:19894643)
• the UV-induced inactivation of ALDH3A1 is a result of non-native aggregation and associated structural changes rather than specific damage to the active site Cys (PMID:21203538)
• Antihypertensives, nonopioid analgesics and hormonal contraceptives significantly affect the salivary ALDH3A1 activity. (PMID:21229876)
• through modulation of PPARgamma or ALDH3A1, it may be possible to reduce cell proliferation in tumor cells or stimulate cell proliferation in normal cells during tissue regeneration. (PMID:21251908)
• ALDH3A1 provides exceptional protection from the adverse effects of pathophysiological concentrations of 4-HNE such as may occur during periods of oxidative stress (PMID:22406320)
• No correlation between ALDH3A1 expression and patient survival or tumour recurrence was observed.In conclusion, ALDH3A1 is a marker of activation of the Wnt/ss-catenin pathway in hepatocellular carcinoma (PMID:24276407)
• SiRNA-mediated suppression of ALDH3A1 blocked ALDH enzymatic activity and augmented cytotoxicity in CSE-exposed cells. (PMID:24316006)
• While ALDH3A1 was not found in prostate glands, it was present in prostatic intraepithelial neoplasia, further increased in carcinomas, and upregulated in lymphatic metastases. ALDH3A1 increased in DU145-cell-derived lung metastasis vs. local xenografts. (PMID:24762960)
• Reported increased expression of ALDH3A1, PDIA3, and PRDX2 in pterygia using a proteomic approach. These proteins are presumed to have a protective role against oxidative stress-induced apoptosis. (PMID:25221425)
• Down-regulation of ALDH3 activity in trophoblast stem cells initiates trophoblast differentiation during placental development. (PMID:26124079)
• ALDH3A1 has a role in the maintenance of corneal epithelial homeostasis by simultaneously modulating proliferation and differentiation through both enzymatic and non-enzymatic mechanisms (PMID:26751691)
• ALDH3A1 confers a multi-modality resistance phenotype in MCF-7 cells (PMID:27276244)
• ALDH-3A1 expression correlates well with gastric cancer dysplasia and grades, differentiation, lymph node metastasis and cancer stage. (PMID:27279633)
• Molecular docking analysis depicted that Sulforaphane fits into the active site of ALDH3A1, and facilitates the catalytic mechanism of the enzyme. (PMID:27997560)
• ALDH3A1 appears to play an essential role in protecting cellular proteins against aggregation under stress conditions (PMID:28526614)
• higher expression in fetal growth restriction-associated placentas but localized specifically to extravillous trophoblasts (PMID:31138432)
• Gastric cancer depends on aldehyde dehydrogenase 3A1 for fatty acid oxidation. (PMID:31705020)
• Aldehyde dehydrogenase 3A1 confers oxidative stress resistance accompanied by altered DNA damage response in human corneal epithelial cells. (PMID:32006654)
• Exosomes carrying ALDOA and ALDH3A1 from irradiated lung cancer cells enhance migration and invasion of recipients by accelerating glycolysis. (PMID:32297178)
• Association with Corneal Remodeling Related Genes, ALDH3A1, LOX, and SPARC Genes Variations in Korean Keratoconus Patients. (PMID:33596621)
• ALDH3A1 overexpression in OSCC inhibits inflammation via phospho-Ser727 at STAT3 in tumor-associated macrophages. (PMID:35188323)
• Hypoxia-induced ALDH3A1 promotes the proliferation of non-small-cell lung cancer by regulating energy metabolism reprogramming. (PMID:37730658)
• These findings suggest that a high level of expression of ALDH3 in cancerous liver tissues resulted from the expression or activation of at least two nuclear proteins reacting to the ALDH3 promoter region. (PMID:9855707)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	aldh3a2a	ENSDARG00000028259
danio_rerio	aldh3a2b	ENSDARG00000029381
danio_rerio	aldh3b4	ENSDARG00000035606
danio_rerio	aldh9a1b	ENSDARG00000037061
mus_musculus	Aldh3a1	ENSMUSG00000019102
rattus_norvegicus	Aldh3a1	ENSRNOG00000002331
drosophila_melanogaster	CG8665	FBGN0032945
drosophila_melanogaster	CG31075	FBGN0051075
caenorhabditis_elegans		WBGENE00000107
caenorhabditis_elegans		WBGENE00000108
caenorhabditis_elegans		WBGENE00000109
caenorhabditis_elegans		WBGENE00000110
caenorhabditis_elegans		WBGENE00000111

Paralogs (17): ALDH3B1 (ENSG00000006534), ALDH3A2 (ENSG00000072210), 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), ALDH1A1 (ENSG00000165092), ALDH1A3 (ENSG00000184254)

Protein

Protein identifiers

Aldehyde dehydrogenase, dimeric NADP-preferring — P30838 (reviewed: P30838)

Alternative names: ALDHIII, Aldehyde dehydrogenase 3, Aldehyde dehydrogenase family 3 member A1

All UniProt accessions (9): P30838, A8MYB8, C9JKT2, C9JMC5, E9PNN6, I3L1H6, I3L3I9, I3L3W9, I3L4E5

UniProt curated annotations — full annotation on UniProt →

Function. ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde. They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation. Oxidizes medium and long chain aldehydes into non-toxic fatty acids. Preferentially oxidizes aromatic aldehyde substrates. Comprises about 50 percent of corneal epithelial soluble proteins. May play a role in preventing corneal damage caused by ultraviolet light.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. High levels in stomach, esophagus and lung; low level in the liver and kidney.

Similarity. Belongs to the aldehyde dehydrogenase family.

RefSeq proteins (4): NP_000682, NP_001128639, NP_001128640, NP_001317079 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012394	Aldehyde_DH_NAD(P)	Family
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 1.2.1.5 — aldehyde dehydrogenase [NAD(P)+] (BRENDA: 19 organisms, 218 substrates, 93 inhibitors, 198 Km, 45 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
NAD+	0.003–35	30
NADP+	0.01–260	22
BENZALDEHYDE	0.013–4.15	17
ACETALDEHYDE	0.0002–393.4	16
PROPANAL	0.0004–19.06	14
CHLOROACETALDEHYDE	0.01–0.46	7
3,4-DIHYDROXYPHENYLACETALDEHYDE	0.0004–0.015	5
2-BROMOBENZALDEHYDE	0.012–0.379	4
2-FLUOROBENZALDEHYDE	0.008–0.822	4
PROPIONALDEHYDE	0.46–12	4
2-CHLOROBENZALDEHYDE	0.006–0.063	3
4-BROMOBENZALDEHYDE	0.039–0.617	3
4-CHLOROBENZALDEHYDE	0.031–1.159	3
4-FLUOROBENZALDEHYDE	0.012–2.057	3
4-IODOBENZALDEHYDE	0.081–1.103	3

Catalyzed reactions (Rhea), 2 shown:

• an aldehyde + NAD(+) + H2O = a carboxylate + NADH + 2 H(+) (RHEA:16185)
• octanal + NAD(+) + H2O = octanoate + NADH + 2 H(+) (RHEA:44100)

UniProt features (59 total): helix 23, strand 16, sequence conflict 4, turn 4, sequence variant 3, modified residue 3, active site 2, initiator methionine 1, chain 1, mutagenesis site 1, binding site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
3SZA	X-RAY DIFFRACTION	1.48
3SZB	X-RAY DIFFRACTION	1.51
8BB8	X-RAY DIFFRACTION	1.8
4L2O	X-RAY DIFFRACTION	1.94
9IG2	X-RAY DIFFRACTION	2.05
4L1O	X-RAY DIFFRACTION	2.3
4H80	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30838-F1	97.89	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 (2): 210; 244

Ligand- & substrate-binding residues (1): 188–193

Post-translational modifications (3): 2, 178, 194

Mutagenesis-validated functional residues (1):

Position	Phenotype
244	abolishes activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-211945	Phase I - Functionalization of compounds
R-HSA-1430728	Metabolism
R-HSA-211859	Biological oxidations

MSigDB gene sets: 136 (showing top): MODULE_93, REACTOME_BIOLOGICAL_OXIDATIONS, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, MODULE_70, WEINMANN_ADAPTATION_TO_HYPOXIA_UP, YAN_ESCAPE_FROM_ANOIKIS, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, GERY_CEBP_TARGETS, KEGG_HISTIDINE_METABOLISM, MARTINEZ_RB1_TARGETS_DN, MODULE_213, MODULE_373, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ALDEHYDE_METABOLIC_PROCESS, MODULE_464

GO Biological Process (3): aldehyde metabolic process (GO:0006081), lipid metabolic process (GO:0006629), xenobiotic metabolic process (GO:0006805)

GO Molecular Function (8): 3-chloroallyl aldehyde dehydrogenase activity (GO:0004028), aldehyde dehydrogenase (NAD+) activity (GO:0004029), aldehyde dehydrogenase [NAD(P)+] activity (GO:0004030), alcohol dehydrogenase (NADP+) activity (GO:0008106), benzaldehyde dehydrogenase (NAD+) activity (GO:0018479), 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): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Biological oxidations	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
metabolic process	2
oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor	2
cytoplasm	2
primary metabolic process	1
cellular response to xenobiotic stimulus	1
aldehyde dehydrogenase [NAD(P)+] activity	1
alcohol dehydrogenase [NAD(P)+] activity	1
aldehyde dehydrogenase (NAD+) activity	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on the aldehyde or oxo group of donors	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

3803 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALDH3A1	KERA	O60938	760
ALDH3A1	CYP1A1	P04798	623
ALDH3A1	CYP1B1	Q16678	620
ALDH3A1	ADH4	P08319	553
ALDH3A1	KRT12	Q99456	549
ALDH3A1	AKR1C1	P52896	546
ALDH3A1	AKR1B10	O60218	545
ALDH3A1	AKR1B1	P15121	532
ALDH3A1	NQO1	P15559	532
ALDH3A1	ADH7	P40394	530
ALDH3A1	AHR	P35869	507
ALDH3A1	ADH5	P11766	506
ALDH3A1	ALDH18A1	P54886	503
ALDH3A1	ADH1B	P00325	488
ALDH3A1	KRT3	P12035	488

IntAct

45 interactions, top by confidence:

A	B	Type	Score
ALDH3A1	RCCD1	psi-mi:“MI:0914”(association)	0.640
FKBP6	ALDH3A1	psi-mi:“MI:0915”(physical association)	0.560
FRMD1	A2ML1	psi-mi:“MI:0914”(association)	0.530
ALDH3A1	IGLL5	psi-mi:“MI:0914”(association)	0.530
ACAD9	PPL	psi-mi:“MI:0914”(association)	0.530
UCP2	CST4	psi-mi:“MI:0914”(association)	0.530
ALDH3A1	POT1	psi-mi:“MI:0915”(physical association)	0.510
ALDH3A1	SRF	psi-mi:“MI:0915”(physical association)	0.370
ALDH3A1	CYHR1	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
GPR18	ARG1	psi-mi:“MI:0914”(association)	0.350
	AP3B1	psi-mi:“MI:0914”(association)	0.350
OR13C3	POTEF	psi-mi:“MI:0914”(association)	0.350
SRRT	A2ML1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	A2ML1	psi-mi:“MI:0914”(association)	0.350
HSF2	A2ML1	psi-mi:“MI:0914”(association)	0.350
PRXL2A	A2ML1	psi-mi:“MI:0914”(association)	0.350
EBF2	LILRA5	psi-mi:“MI:0914”(association)	0.350
GPR18	FLG	psi-mi:“MI:0914”(association)	0.350
CPN1	ALDH3A1	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
PIGT	A2ML1	psi-mi:“MI:0914”(association)	0.350
CORO1C	A2ML1	psi-mi:“MI:0914”(association)	0.350
FNDC5	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (92): ALDH3A1 (Affinity Capture-MS), ALDH3A1 (Affinity Capture-MS), ALDH3A1 (Affinity Capture-MS), ALDH3A1 (Affinity Capture-MS), ALDH3A1 (Affinity Capture-Western), FBXL12 (Affinity Capture-Western), ALDH3A1 (Biochemical Activity), IGHG3 (Affinity Capture-MS), ZNF446 (Affinity Capture-MS), ALDH3A2 (Affinity Capture-MS), IGHG2 (Affinity Capture-MS), IGKC (Affinity Capture-MS), ALDH3A1 (Affinity Capture-MS), IGLL5 (Affinity Capture-MS), HIST2H2AC (Affinity Capture-MS)

ESM2 similar proteins: A1VTR9, A3RF36, A4G8E9, A5G906, A6VZ85, A9LYY9, B5EEI4, B5FJX5, B5R4S6, B5R5R9, B8FUB6, B9M0D6, C0QLF1, C6BSC1, C6E7L9, E9Q3E1, J3QMK6, O14293, O93344, O94788, P11883, P12693, P30838, P30839, P30907, P39616, P42269, P46329, P47739, P47740, P51648, P54115, P81178, Q02XW0, Q24XR6, Q2YBP9, Q311G6, Q54DG1, Q5RF60, Q5XI42

Diamond homologs: A0A7W3RCJ3, A3M365, A3RF36, A4JJG5, A4XPI6, A7FKL5, A9AN00, B0RNV0, B0V944, B0VST2, B2FQ90, B2HV80, B4SHW0, B7GYG4, B7I896, C6KEM4, C7A2A0, D5E1S7, E9Q3E1, F6IBC7, J3QMK6, O04895, O05619, O24174, O59808, O74187, O86447, P08157, P0DPF0, P11883, P12693, P17202, P25553, P30838, P30839, P30840, P30907, P32872, P39616, P40108

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
FBXL12	“down-regulates quantity by destabilization”	ALDH3A1	binding
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	ALDH3A1	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	38
Likely benign	5
Benign	5

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1047863	GRCh37/hg19 17p11.2(chr17:17145361-20137943)	Pathogenic
145065	GRCh38/hg38 17p11.2(chr17:16854250-20492169)x3	Pathogenic
149203	GRCh38/hg38 17p11.2(chr17:16854250-20492214)x3	Pathogenic
253648	GRCh37/hg19 17p11.2(chr17:16654302-20261250)x1	Pathogenic
2442791	NM_000691.5(ALDH3A1):c.703G>A (p.Gly235Arg)	Likely pathogenic

SpliceAI

2224 predictions. Top by Δscore:

Variant	Effect	Δscore
17:19738449:GTTCC:G	acceptor_gain	1.0000
17:19738450:TTCC:T	acceptor_gain	1.0000
17:19738451:TCC:T	acceptor_gain	1.0000
17:19738452:CC:C	acceptor_gain	1.0000
17:19738452:CCC:C	acceptor_gain	1.0000
17:19738453:CC:C	acceptor_gain	1.0000
17:19738453:CCT:C	acceptor_loss	1.0000
17:19738454:C:CA	acceptor_loss	1.0000
17:19738454:C:CC	acceptor_gain	1.0000
17:19738454:C:T	acceptor_gain	1.0000
17:19738457:C:CT	acceptor_gain	1.0000
17:19738458:G:T	acceptor_gain	1.0000
17:19739504:CCAC:C	donor_loss	1.0000
17:19739505:CACCT:C	donor_loss	1.0000
17:19739506:A:T	donor_loss	1.0000
17:19739507:C:CG	donor_loss	1.0000
17:19739551:CG:C	donor_gain	1.0000
17:19739670:GGGGG:G	acceptor_gain	1.0000
17:19739671:GGGG:G	acceptor_gain	1.0000
17:19739672:GGG:G	acceptor_gain	1.0000
17:19739673:GG:G	acceptor_gain	1.0000
17:19739674:GC:G	acceptor_loss	1.0000
17:19739675:C:CA	acceptor_loss	1.0000
17:19739675:C:CC	acceptor_gain	1.0000
17:19739681:C:CT	acceptor_gain	1.0000
17:19739682:A:T	acceptor_gain	1.0000
17:19740331:CGCA:C	donor_loss	1.0000
17:19740332:GCAC:G	donor_loss	1.0000
17:19740333:CACC:C	donor_loss	1.0000
17:19740475:CTC:C	acceptor_gain	1.0000

AlphaMissense

2979 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:19739616:G:C	F336L	0.997
17:19739616:G:T	F336L	0.997
17:19739618:A:G	F336L	0.997
17:19742094:G:T	A200D	0.995
17:19742042:G:C	C217W	0.994
17:19743281:G:C	N115K	0.994
17:19743281:G:T	N115K	0.994
17:19743286:A:G	W114R	0.994
17:19743286:A:T	W114R	0.994
17:19742116:C:A	G193W	0.993
17:19742611:C:A	K138N	0.993
17:19742611:C:G	K138N	0.993
17:19742630:C:A	G132V	0.993
17:19743232:C:A	G132W	0.993
17:19739614:C:T	G337E	0.992
17:19741178:C:T	G241D	0.992
17:19741208:C:G	R231P	0.992
17:19738416:G:C	S418R	0.991
17:19738416:G:T	S418R	0.991
17:19738418:T:G	S418R	0.991
17:19739006:G:C	F402L	0.991
17:19739006:G:T	F402L	0.991
17:19739008:A:G	F402L	0.991
17:19739523:G:C	F367L	0.991
17:19739523:G:T	F367L	0.991
17:19739525:A:G	F367L	0.991
17:19739623:T:A	E334V	0.991
17:19741178:C:A	G241V	0.991
17:19742048:A:C	S215R	0.991
17:19742048:A:T	S215R	0.991

dbSNP variants (sampled 300 via entrez): RS1000049285 (17:19749241 T>C), RS1000222912 (17:19744520 C>A,T), RS1000557126 (17:19750189 G>A), RS1000858181 (17:19745177 G>A,C,T), RS1001625635 (17:19749717 C>T), RS1001794550 (17:19743764 G>A,C), RS1002060438 (17:19748715 C>T), RS1002187740 (17:19743913 A>T), RS1002385440 (17:19740031 C>A,T), RS1002414518 (17:19745444 T>G), RS1002722376 (17:19741341 C>G,T), RS1002786298 (17:19742916 C>A,T), RS1002972321 (17:19737875 G>A), RS1003207277 (17:19742751 T>C,G), RS1003572147 (17:19746704 T>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:182290, MIM:148300

GenCC curated gene-disease

Mondo (2): Smith-Magenis syndrome (MONDO:0008434), keratoconus (MONDO:0015486)

Orphanet (3): Smith-Magenis syndrome (Orphanet:819), OBSOLETE: Keratoconus (Orphanet:156071), NON RARE IN EUROPE: Isolated keratoconus (Orphanet:2335)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000563	Keratoconus

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002337_59	Amyotrophic lateral sclerosis (sporadic)	4.000000e-08
GCST005580_271	Intraocular pressure	5.000000e-10
GCST005580_276	Intraocular pressure	9.000000e-10
GCST006585_1078	Blood protein levels	1.000000e-13
GCST007160_29	Refractive astigmatism	9.000000e-06
GCST90013442_28	Keratoconus	9.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D007640	Keratoconus	C11.204.627
D058496	Smith-Magenis Syndrome	C10.281.900; C16.131.077.879; C16.131.260.887; C16.320.180.887

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3542434 (PROTEIN FAMILY), CHEMBL3578 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2228100	Toxicity	3	cyclophosphamide;doxorubicin;fluorouracil	Breast Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2228100	ALDH3A1	3	2.75	1	cyclophosphamide;doxorubicin;fluorouracil

Binding affinities (BindingDB)

41 measured of 67 human assays (67 total across all organisms); most potent 41 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-(4-fluorophenyl)sulfonyl-2-methylbenzimidazole	KI	200 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
1-(4-chlorophenyl)sulfonyl-2-methylbenzimidazole	IC50	300 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
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
1-(4-chloro-3-methylphenyl)sulfonyl-2-methylbenzimidazole	IC50	700 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
2-methyl-1-(4-methylphenyl)sulfonyl-benzimidazole	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
1-(4-fluoro-3-methoxyphenyl)sulfonyl-2-methylbenzimidazole	IC50	900 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
1-(4-chloro-3-methoxyphenyl)sulfonyl-2-methylbenzimidazole	IC50	900 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
1-[1-(4-chlorophenyl)sulfonylbenzimidazol-2-yl]ethanone	IC50	1000 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
MLS-0425609.0001	IC50	1200 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
1-(4-chlorophenyl)sulfonylbenzimidazole	IC50	1500 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
1-(4-methoxy-3-methylphenyl)sulfonyl-2-methylbenzimidazole	IC50	2000 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
1-(4-fluorophenyl)sulfonylbenzimidazole	IC50	2100 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
1-(1,3-benzodioxol-5-yl)-3-(diethylamino)propan-1-one	IC50	3200 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
4-(4-chlorophenoxy)butyl thiocyanate	IC50	3700 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
1-(3,4-difluorophenyl)sulfonylbenzimidazole	IC50	4200 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
3,4-difluoro-N-[(2-nitrophenyl)methyl]aniline	IC50	5200 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
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-fluoro-4-methyl-N-(4-methylsulfonyl-2-nitrophenyl)aniline	IC50	10800 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
1-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-morpholin-4-ylpropan-1-one	IC50	11700 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
N-[4-(4-methylsulfonyl-2-nitroanilino)phenyl]acetamide	IC50	16000 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-N,4-N-dimethyl-1-N-[2-nitro-4-(trifluoromethylsulfonyl)phenyl]benzene-1,4-diamine	IC50	17000 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
4-[4-(difluoromethoxy)anilino]-N-methyl-3-nitrobenzenesulfonamide	IC50	24700 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
2-[4-[2-nitro-4-(propan-2-ylsulfamoyl)anilino]piperidin-1-yl]-N-phenylacetamide	IC50	25600 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
4-(4-fluoroanilino)-N-methyl-3-nitrobenzenesulfonamide	IC50	26000 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
3-nitro-N-propan-2-yl-4-[3-(propan-2-ylamino)anilino]benzenesulfonamide	IC50	26300 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
N-(4-methylsulfonyl-2-nitrophenyl)-2,3-dihydro-1H-inden-5-amine	IC50	26900 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
4-(2,3-dihydro-1H-inden-5-ylamino)-3-nitro-N-propan-2-ylbenzenesulfonamide	IC50	30500 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
4-(4-methoxyanilino)-N-methyl-3-nitrobenzenesulfonamide	IC50	31700 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
MLS-0082307.0001	IC50	50000 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
N-[4-[2-nitro-4-(trifluoromethylsulfonyl)phenoxy]phenyl]acetamide	IC50	100000 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods

ChEMBL bioactivities

93 potent at pChembl≥5 of 125 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.09	Ki	82	nM	CHEMBL1378094
6.96	Ki	110	nM	CHEMBL1378094
6.71	IC50	193	nM	CHEMBL4745360
6.70	Ki	200	nM	CHEMBL1378094
6.70	IC50	200	nM	CHEMBL1378094
6.66	IC50	219	nM	CHEMBL4777582
6.66	IC50	219	nM	CHEMBL4754311
6.62	IC50	241	nM	CHEMBL4753971
6.62	Ki	240	nM	CHEMBL5076191
6.61	IC50	246	nM	CHEMBL4755837
6.61	IC50	246	nM	CHEMBL4791741
6.60	IC50	251	nM	CHEMBL4763602
6.52	IC50	300	nM	CHEMBL3112681
6.52	IC50	300	nM	CHEMBL3128211
6.52	Ki	300	nM	CHEMBL5082977
6.51	IC50	310	nM	CHEMBL1453099
6.49	IC50	327	nM	CHEMBL4752256
6.48	IC50	333	nM	CHEMBL4796029
6.46	IC50	344	nM	CHEMBL4755996
6.44	IC50	360	nM	CHEMBL3128208
6.44	IC50	360	nM	CHEMBL4742685
6.43	IC50	368	nM	CHEMBL4764389
6.42	Ki	380	nM	CHEMBL3128208
6.38	IC50	420	nM	CHEMBL3128209
6.35	IC50	450	nM	CHEMBL3128205
6.34	IC50	460	nM	CHEMBL1328547
6.30	Ki	500	nM	CHEMBL3128208
6.16	IC50	700	nM	CHEMBL3112688
6.16	IC50	700	nM	CHEMBL1411903
6.05	IC50	900	nM	CHEMBL1308268
6.05	IC50	900	nM	CHEMBL3112689
6.03	IC50	930	nM	CHEMBL3128204
6.00	IC50	1000	nM	CHEMBL1492620
5.92	IC50	1200	nM	CHEMBL1521474
5.92	Ki	1200	nM	CHEMBL115581
5.92	IC50	1200	nM	CHEMBL3128216
5.89	IC50	1300	nM	CHEMBL222849
5.89	IC50	1290	nM	CHEMBL5076191
5.84	IC50	1450	nM	CHEMBL4871374
5.82	IC50	1500	nM	CHEMBL1493289
5.82	IC50	1500	nM	CHEMBL3128213
5.82	IC50	1500	nM	CHEMBL3971230
5.82	IC50	1520	nM	CHEMBL4781762
5.80	IC50	1600	nM	CHEMBL467081
5.80	IC50	1600	nM	CHEMBL467080
5.79	IC50	1610	nM	CHEMBL5082977
5.77	IC50	1700	nM	CHEMBL3128215
5.75	IC50	1800	nM	CHEMBL3128217
5.72	IC50	1900	nM	CHEMBL3128214
5.72	IC50	1900	nM	CHEMBL4855040

PubChem BioAssay actives

72 with measured affinity, of 271 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-fluorophenyl)sulfonyl-2-methylbenzimidazole	1068468: Competitive inhibition of human ALDH3A1 using benzaldehyde as substrate by Lineweaver-Burk plot analysis in presence of 1.5 mM NADP+	ki	0.0820	uM
[4-[(5,7-dibromo-2,3-dioxoindol-1-yl)methyl]phenyl]methyl carbamimidothioate;hydrobromide	1702904: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate	ic50	0.1930	uM
[4-[(7-bromo-5-fluoro-2,3-dioxoindol-1-yl)methyl]phenyl]methyl carbamimidothioate;hydrobromide	1702904: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate	ic50	0.2190	uM
[4-[(5,7-dichloro-2,3-dioxoindol-1-yl)methyl]phenyl]methyl carbamimidothioate;hydrobromide	1702904: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate	ic50	0.2190	uM
4-(diethylamino)-3-nitrobenzaldehyde	1826428: Competitive inhibition of N-terminal-His6 tagged recombinant human ALDH3A1 using 4-NBA and NADP+ as substrate by Michaelis-Menten based analysis	ki	0.2400	uM
[4-[(7-fluoro-2,3-dioxoindol-1-yl)methyl]phenyl]methyl carbamimidothioate;hydrobromide	1702904: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate	ic50	0.2410	uM
[4-[[2,3-dioxo-7-(trifluoromethyl)indol-1-yl]methyl]phenyl]methyl carbamimidothioate;hydrobromide	1702904: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate	ic50	0.2460	uM
[4-[(7-fluoro-2,3-dioxoindol-1-yl)methyl]phenyl]methyl carbamimidoselenoate;hydrobromide	1702904: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate	ic50	0.2460	uM
[4-[[2,3-dioxo-7-(trifluoromethyl)indol-1-yl]methyl]phenyl]methyl carbamimidoselenoate;hydrobromide	1702904: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate	ic50	0.2510	uM
1-[[4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl]methyl]indole-2,3-dione	1074882: Inhibition of full length human ALDH3A1 expressed in Escherichia coli BL21 (DE3) using benzaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NADP+	ic50	0.3000	uM
4-(dipropylamino)-3-nitrobenzaldehyde	1826428: Competitive inhibition of N-terminal-His6 tagged recombinant human ALDH3A1 using 4-NBA and NADP+ as substrate by Michaelis-Menten based analysis	ki	0.3000	uM
1-(4-chlorophenyl)sulfonyl-2-methylbenzimidazole	1068474: Inhibition of human ALDH3A1-mediated benzaldehyde oxidation preincubated for 1 min followed by substrate addition by spectrophotometric analysis	ic50	0.3000	uM
1-[(E)-3-phenylprop-2-enyl]indole-2,3-dione	1074882: Inhibition of full length human ALDH3A1 expressed in Escherichia coli BL21 (DE3) using benzaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NADP+	ic50	0.3100	uM
[4-[(5,7-dichloro-2,3-dioxoindol-1-yl)methyl]phenyl]methyl carbamimidoselenoate;hydrobromide	1702904: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate	ic50	0.3270	uM
[4-[(5,7-dibromo-2,3-dioxoindol-1-yl)methyl]phenyl]methyl carbamimidoselenoate;hydrobromide	1702904: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate	ic50	0.3330	uM
[4-[(5-bromo-2,3-dioxoindol-1-yl)methyl]phenyl]methyl carbamimidoselenoate;hydrobromide	1702904: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate	ic50	0.3440	uM
[4-[[2,3-dioxo-5-(trifluoromethyl)indol-1-yl]methyl]phenyl]methyl carbamimidothioate;hydrobromide	1702904: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate	ic50	0.3600	uM
7-bromo-5-methyl-1H-indole-2,3-dione	1074882: Inhibition of full length human ALDH3A1 expressed in Escherichia coli BL21 (DE3) using benzaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NADP+	ic50	0.3600	uM
[4-[(7-bromo-5-fluoro-2,3-dioxoindol-1-yl)methyl]phenyl]methyl carbamimidoselenoate;hydrobromide	1702904: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate	ic50	0.3680	uM
1-pentylindole-2,3-dione	1074882: Inhibition of full length human ALDH3A1 expressed in Escherichia coli BL21 (DE3) using benzaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NADP+	ic50	0.4200	uM
1-(2-phenylethyl)indole-2,3-dione	1074882: Inhibition of full length human ALDH3A1 expressed in Escherichia coli BL21 (DE3) using benzaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NADP+	ic50	0.4500	uM
1-(3-phenylpropyl)indole-2,3-dione	1074882: Inhibition of full length human ALDH3A1 expressed in Escherichia coli BL21 (DE3) using benzaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NADP+	ic50	0.4600	uM
1-(4-chloro-3-methylphenyl)sulfonyl-2-methylbenzimidazole	1068474: Inhibition of human ALDH3A1-mediated benzaldehyde oxidation preincubated for 1 min followed by substrate addition by spectrophotometric analysis	ic50	0.7000	uM
2-methyl-1-(4-methylphenyl)sulfonylbenzimidazole	1068474: Inhibition of human ALDH3A1-mediated benzaldehyde oxidation preincubated for 1 min followed by substrate addition by spectrophotometric analysis	ic50	0.7000	uM
1-(4-chloro-3-methoxyphenyl)sulfonyl-2-methylbenzimidazole	1068474: Inhibition of human ALDH3A1-mediated benzaldehyde oxidation preincubated for 1 min followed by substrate addition by spectrophotometric analysis	ic50	0.9000	uM
1-(4-fluoro-3-methoxyphenyl)sulfonyl-2-methylbenzimidazole	1068474: Inhibition of human ALDH3A1-mediated benzaldehyde oxidation preincubated for 1 min followed by substrate addition by spectrophotometric analysis	ic50	0.9000	uM
1-[(4-benzylpiperazin-1-yl)methyl]indole-2,3-dione	1074882: Inhibition of full length human ALDH3A1 expressed in Escherichia coli BL21 (DE3) using benzaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NADP+	ic50	0.9300	uM
1-[1-(4-chlorophenyl)sulfonylbenzimidazol-2-yl]ethanone	1068474: Inhibition of human ALDH3A1-mediated benzaldehyde oxidation preincubated for 1 min followed by substrate addition by spectrophotometric analysis	ic50	1.0000	uM
1-(4-chlorophenyl)sulfonylbenzimidazol-2-amine	1068474: Inhibition of human ALDH3A1-mediated benzaldehyde oxidation preincubated for 1 min followed by substrate addition by spectrophotometric analysis	ic50	1.2000	uM
1-[[4-[(3-methoxyphenyl)methyl]piperazin-1-yl]methyl]indole-2,3-dione	1074882: Inhibition of full length human ALDH3A1 expressed in Escherichia coli BL21 (DE3) using benzaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NADP+	ic50	1.2000	uM
1-benzylindole-2,3-dione	1074876: Inhibition of human ALDH3A1 using benzaldehyde as substrate by Lineweaver-Burk plot analysis	ki	1.2000	uM
1-(morpholin-4-ylmethyl)indole-2,3-dione	1074882: Inhibition of full length human ALDH3A1 expressed in Escherichia coli BL21 (DE3) using benzaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NADP+	ic50	1.3000	uM
[4-[[1-[(3-chlorophenyl)methyl]benzimidazol-2-yl]methyl]piperazin-1-yl]-cyclopropylmethanone	1766112: Inhibition of human ALDH3A1 assessed as NADH formation using propionaldehyde as substrate by spectrophotometry	ic50	1.4500	uM
1-[[4-[(4-fluorophenyl)methyl]piperazin-1-yl]methyl]indole-2,3-dione	1074882: Inhibition of full length human ALDH3A1 expressed in Escherichia coli BL21 (DE3) using benzaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NADP+	ic50	1.5000	uM
1-(4-chlorophenyl)sulfonylbenzimidazole	1068474: Inhibition of human ALDH3A1-mediated benzaldehyde oxidation preincubated for 1 min followed by substrate addition by spectrophotometric analysis	ic50	1.5000	uM
[4-[[2,3-dioxo-5-(trifluoromethyl)indol-1-yl]methyl]phenyl]methyl carbamimidoselenoate;hydrobromide	1702904: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate	ic50	1.5200	uM
1-[(4-methylpiperazin-1-yl)methyl]indole-2,3-dione	1074882: Inhibition of full length human ALDH3A1 expressed in Escherichia coli BL21 (DE3) using benzaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NADP+	ic50	1.6000	uM
1-[[3-[(2,3-dioxoindol-1-yl)methyl]imidazolidin-1-yl]methyl]indole-2,3-dione	1074882: Inhibition of full length human ALDH3A1 expressed in Escherichia coli BL21 (DE3) using benzaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NADP+	ic50	1.6000	uM
1-[[4-[(3-chlorophenyl)methyl]piperazin-1-yl]methyl]indole-2,3-dione	1074882: Inhibition of full length human ALDH3A1 expressed in Escherichia coli BL21 (DE3) using benzaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NADP+	ic50	1.7000	uM
1-[[4-[(2-fluorophenyl)methyl]piperazin-1-yl]methyl]indole-2,3-dione	1074882: Inhibition of full length human ALDH3A1 expressed in Escherichia coli BL21 (DE3) using benzaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NADP+	ic50	1.8000	uM
[4-[[1-[(2-chlorophenyl)methyl]benzimidazol-2-yl]methyl]piperazin-1-yl]-cyclopropylmethanone	1766112: Inhibition of human ALDH3A1 assessed as NADH formation using propionaldehyde as substrate by spectrophotometry	ic50	1.9000	uM
1-[[4-[(3-fluorophenyl)methyl]piperazin-1-yl]methyl]indole-2,3-dione	1074882: Inhibition of full length human ALDH3A1 expressed in Escherichia coli BL21 (DE3) using benzaldehyde as substrate preincubated for 2 mins followed by substrate addition by spectrophotometry in presence of NADP+	ic50	1.9000	uM
1-(4-methoxy-3-methylphenyl)sulfonyl-2-methylbenzimidazole	1068474: Inhibition of human ALDH3A1-mediated benzaldehyde oxidation preincubated for 1 min followed by substrate addition by spectrophotometric analysis	ic50	2.0000	uM
1-(4-fluorophenyl)sulfonylbenzimidazole	1068474: Inhibition of human ALDH3A1-mediated benzaldehyde oxidation preincubated for 1 min followed by substrate addition by spectrophotometric analysis	ic50	2.1000	uM
cyclopropyl-[4-[[1-(3-methylbut-2-enyl)benzimidazol-2-yl]methyl]piperazin-1-yl]methanone	1766112: Inhibition of human ALDH3A1 assessed as NADH formation using propionaldehyde as substrate by spectrophotometry	ic50	2.1500	uM
1-[4-[[1-[(3-methylphenyl)methyl]benzimidazol-2-yl]methyl]piperazin-1-yl]propan-1-one	1766112: Inhibition of human ALDH3A1 assessed as NADH formation using propionaldehyde as substrate by spectrophotometry	ic50	2.3100	uM
[4-[(5-fluoro-2,3-dioxoindol-1-yl)methyl]phenyl]methyl carbamimidoselenoate;hydrobromide	1702904: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate	ic50	2.3640	uM
cyclopropyl-[4-[[1-[[3-(trifluoromethyl)phenyl]methyl]benzimidazol-2-yl]methyl]piperazin-1-yl]methanone	1766112: Inhibition of human ALDH3A1 assessed as NADH formation using propionaldehyde as substrate by spectrophotometry	ic50	2.6200	uM
[4-[(5-chloro-2,3-dioxoindol-1-yl)methyl]phenyl]methyl carbamimidoselenoate;hydrobromide	1702904: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate	ic50	2.7670	uM
[4-[(5-fluoro-2,3-dioxoindol-1-yl)methyl]phenyl]methyl carbamimidothioate;hydrobromide	1702904: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate	ic50	2.8550	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation, decreases reaction	13
Tetrachlorodibenzodioxin	affects expression, affects cotreatment, increases expression	12
Tobacco Smoke Pollution	affects expression, increases expression	9
Particulate Matter	affects cotreatment, decreases expression, decreases reaction, increases expression, affects expression (+1 more)	8
sodium arsenite	decreases expression, increases abundance, increases expression, affects splicing	7
benzaldehyde	increases oxidation, decreases reaction, affects cotreatment	4
Air Pollutants	affects expression, increases abundance, increases expression	4
bisphenol A	affects expression, decreases expression, decreases methylation	3
4-hydroxy-2-nonenal	affects response to substance, decreases response to substance, increases oxidation	3
Vehicle Emissions	decreases expression, increases abundance, decreases reaction, increases expression	3
Aflatoxin B1	affects expression, increases expression	3
beta-Naphthoflavone	increases expression	3
cobaltous chloride	increases expression, decreases expression, decreases reaction	2
phenanthrene	decreases expression, increases expression	2
dibenzo(a,l)pyrene	decreases expression	2
chloropicrin	increases expression	2
Arsenic Trioxide	increases response to substance, decreases response to substance, decreases reaction	2
Arsenic	decreases expression, increases abundance, increases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Smoke	increases abundance, increases expression	2
Tretinoin	decreases activity, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
ME-344	increases expression	1
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, increases expression	1
TAK-243	increases sumoylation	1
PF-06840003	decreases reaction, increases expression	1
methyleugenol	increases expression	1
propionaldehyde	increases metabolic processing	1
propylparaben	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1

ChEMBL screening assays

42 unique, capped per target: 38 binding, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3118113	Binding	Inhibition of ALDH3A1 in human SF-767 cells assessed as reduction of mafosfamide ED50 at 10 uM after 19 hrs by MTT assay relative to control	Selective ALDH3A1 inhibition by benzimidazole analogues increase mafosfamide sensitivity in cancer cells. — J Med Chem
CHEMBL5049241	ADMET	Substrate activity at N-terminal-His6 tagged recombinant human ALDH3A1 at 10 uM in presence of NADPH by fluorimetric analysis relative to 4-NBA	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

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7K0	Ubigene A-549 ALDH3A1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01485211	PHASE4	COMPLETED	Corneal Thickness Changes During Corneal Collagen Cross-linking With Ultraviolet-A Irradiation and Riboflavin
NCT02119039	PHASE4	COMPLETED	Effect of CACICOL20 on Corneal Epithelial Healing After Cross-linking in Patients With Keratoconus
NCT03245853	PHASE4	COMPLETED	Epi-On Corneal Crosslinking for Keratoconus
NCT03429569	PHASE4	UNKNOWN	Cross-Linking ACcéléré Iontophorèse Confocal kératocONE
NCT04427956	PHASE4	COMPLETED	Corneal Crosslinking Treatment Study
NCT07474870	PHASE4	NOT_YET_RECRUITING	Outcomes of CTAK Surgery
NCT00371202	PHASE3	UNKNOWN	Comparison of Penetrating Keratoplasty and Deep Lamellar Keratoplasty With the Big Bubble Technique for Keratoconus
NCT00647699	PHASE3	COMPLETED	Corneal Collagen Cross-linking for Progressive Keratoconus
NCT00815256	PHASE3	UNKNOWN	Safety and Effectiveness of Collagen Cross Linking in Progressive Mild and Moderate Keratoconus
NCT00887900	PHASE3	COMPLETED	Deep Anterior Lamellar Keratoplasty (DALK)
NCT01112072	PHASE3	UNKNOWN	Corneal Collagen Crosslinking and Intacs for Keratoconus and Ectasia
NCT01152541	PHASE3	UNKNOWN	Corneal Collagen Crosslinking for Progressive Keratoconus and Ectasia Using Riboflavin/Dextran and Hypotonic Riboflavin
NCT01190306	PHASE3	TERMINATED	Safety Study of the VEGA UV-A System to Treat Keratoconus
NCT01344187	PHASE3	COMPLETED	Safety and Efficacy Study of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT01459679	PHASE3	TERMINATED	Safety & Efficacy of Corneal Collagen Cross-Linking in Eyes With Keratoconus or Corneal Ectasia After Refractive Surgery
NCT01464268	PHASE3	UNKNOWN	Transepithelial Corneal Collagen Crosslinking for Keratoconus and Corneal Ectasia
NCT01604135	PHASE3	ACTIVE_NOT_RECRUITING	Collagen Crosslinking for Keratoconus - a Randomized Controlled Clinical Trial
NCT01643226	PHASE3	COMPLETED	Safety and Efficacy Study of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT01672814	PHASE3	COMPLETED	Microwave Treatment and Corneal Collagen Crosslinking for Keratoconus
NCT01682993	PHASE3	TERMINATED	Corneal Cross Linking and Topography Guided Excimer Laser Treatment
NCT01972854	PHASE3	TERMINATED	Safety and Efficacy of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT02613780	PHASE3	UNKNOWN	Refractive Treatment of Early Keratoconus
NCT02638376	PHASE3	UNKNOWN	Evaluating the Safety and Efficacy of the KXL System for Corneal Collagen Cross-Linking in Eyes Having Keratoconus
NCT03080077	PHASE3	UNKNOWN	Safety and Effectiveness of Corneal Crosslinking (CXL): Keratoconus and Post-Refractive Ectasia
NCT03187912	PHASE3	COMPLETED	Accelerated Corneal Cross-linking With Different Riboflavin Solutions
NCT03442751	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Epi-on Corneal Cross-linking in Eyes With Progressive Keratoconus
NCT03858036	PHASE3	UNKNOWN	Corneal Collagen Cross-Linking (CXL) Performed With Epi-ON Versus Epi-OFF in Eyes With Keratoconus and Other Corneal Ectatic Disorders
NCT04897503	PHASE3	UNKNOWN	Corneal Collagen Crosslinking for Keratoconus and Ectasia Using Riboflavin/Dextran or Riboflavin/Methylcellulose
NCT04905108	PHASE3	UNKNOWN	Transepithelial (Epi-on) Corneal Collagen Crosslinking to Treat Keratoconus and Corneal Ectasia
NCT05027295	PHASE3	UNKNOWN	Accelerated Corneal Collagen Crosslinking for Keratoconus and Ectasia Using Pulse or Continuous UV-A Light
NCT06100939	PHASE3	ACTIVE_NOT_RECRUITING	Epithelium-On Corneal Cross-linking in Subjects 8 to 45 Years of Age With Keratoconus
NCT06100952	PHASE3	ACTIVE_NOT_RECRUITING	Epithelium-On Corneal Cross-linking in Subjects 8 to 45 Years of Age with Keratoconus
NCT06450470	PHASE3	RECRUITING	Use of a Freeze-dried Amniotic Membrane Post Crosslinking in Subjects With Progressive Keratoconus
NCT06601101	PHASE3	RECRUITING	Effects of Topical Insulin on Corneal Epithelium Healing After Corneal Crosslinking in Patients With Keratoconus
NCT07124910	PHASE3	RECRUITING	Comparison of Epi-ON Corneal Collagen Crosslinking Performed Using an 18-Minute UVA Exposure vs. a 24-Minute UVA Exposure on Eyes With Ectatic Corneal Diseases
NCT07135167	PHASE3	RECRUITING	Compassionate Use Study of Epi-ON Corneal Collagen Crosslinking Performed Using UVA Exposure on Eyes With Ectatic Corneal Diseases for Subjects With Down Syndrome
NCT00409955	PHASE2	COMPLETED	Lamellar Transplant With Lyophilized Corneas
NCT00925327	PHASE2	UNKNOWN	Safety and Effectiveness of the UV-X System for Corneal Collagen Cross-Linking for Compassionate Treatment in Pediatric Patients With Progressive Keratoconus
NCT01143389	PHASE2	COMPLETED	Corneal Crosslinking in Patients With Keratoconus and Post-Refractive Ectasia
NCT01181219	PHASE2	COMPLETED	Transepithelial Corneal Collagen Cross-linking (CXL) in Treatment of Keratoconus