ALDH1B1

Summary

ALDH1B1 (aldehyde dehydrogenase 1 family member B1, HGNC:407) is a protein-coding gene on chromosome 9p13.1, encoding Aldehyde dehydrogenase X, mitochondrial (P30837). ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde.

This protein belongs to the aldehyde dehydrogenases family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. This gene does not contain introns in the coding sequence. The variation of this locus may affect the development of alcohol-related problems.

Source: NCBI Gene 219 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 96 total — 8 pathogenic, 2 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_000692

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:407
Approved symbol	ALDH1B1
Name	aldehyde dehydrogenase 1 family member B1
Location	9p13.1
Locus type	gene with protein product
Status	Approved
Aliases	ALDHX
Ensembl gene	ENSG00000137124
Ensembl biotype	protein_coding
Entrez	219

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000377698, ENST00000635162, ENST00000897464, ENST00000897465, ENST00000928834, ENST00000969483

RefSeq mRNA: 1 — MANE Select: NM_000692 NM_000692

CCDS: CCDS6615

Canonical transcript exons

ENST00000377698 — 2 exons

Exon	Start	End
ENSE00001474883	38395740	38398661
ENSE00001474887	38392702	38392807

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 99.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.6276 / max 413.5930, expressed in 1754 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96755	26.6276	1754

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	99.44	silver quality
right coronary artery	UBERON:0001625	97.46	gold quality
tendon of biceps brachii	UBERON:0008188	97.39	gold quality
popliteal artery	UBERON:0002250	97.20	gold quality
tibial artery	UBERON:0007610	97.19	gold quality
aorta	UBERON:0000947	96.81	gold quality
thoracic aorta	UBERON:0001515	96.52	gold quality
ascending aorta	UBERON:0001496	96.51	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.05	gold quality
lower esophagus	UBERON:0013473	94.97	gold quality
descending thoracic aorta	UBERON:0002345	94.91	gold quality
left coronary artery	UBERON:0001626	94.54	gold quality
coronary artery	UBERON:0001621	93.41	gold quality
left uterine tube	UBERON:0001303	93.37	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.10	gold quality
smooth muscle tissue	UBERON:0001135	92.39	gold quality
blood vessel layer	UBERON:0004797	92.21	gold quality
rectum	UBERON:0001052	92.09	gold quality
mucosa of stomach	UBERON:0001199	92.01	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.86	gold quality
gall bladder	UBERON:0002110	91.84	gold quality
saphenous vein	UBERON:0007318	91.63	gold quality
right lobe of liver	UBERON:0001114	91.25	gold quality
liver	UBERON:0002107	90.15	gold quality
gastrocnemius	UBERON:0001388	89.88	gold quality
muscle of leg	UBERON:0001383	89.58	gold quality
transverse colon	UBERON:0001157	89.24	gold quality
adrenal tissue	UBERON:0018303	89.23	gold quality
vermiform appendix	UBERON:0001154	88.82	gold quality
body of uterus	UBERON:0009853	88.80	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	17.29
E-ANND-3	yes	9.34
E-HCAD-11	yes	9.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting ALDH1B1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-6770-5P	98.97	66.76	1853

Literature-anchored findings (GeneRIF, showing 24)

• Retinoic-acid-induced RAR-CAK signaling events appear to proceed intrinsically during granulocytic development of normal primitive hematopoietic cells. ALDH-governed RA availability may mediate this process by initiating RAR-CAK signaling. (PMID:17628022)
• ALDH1b1 ala69val was associated with diastolic blood pressure in a Caucasian population sample (PMID:18782342)
• a common SNP encoding ALDH1b1 (rs2228093) was found to be significantly associated with alcohol-induced hypersensitivity. (PMID:20205700)
• An ALDHX model based on the crystal structure of human ALDH2, reveals similarities with the previously described ALDH structures. Analyses indicate a close structural and functional relationship between the two isoenzymes of human origin (PMID:20955166)
• ALDH1B1 is more profoundly expressed in the adenocarcinomas examined in this study relative to ALDH1A1 and that ALDH1B1 is dramatically upregulated in human colonic adenocarcinoma, making it a potential biomarker for human colon cancer. (PMID:21216231)
• Molecular modeling studies examining predicted protein-protein interactions indicated that heterotetramerization between ALDH2 and ALDH1B1 subunits was highly probable and may partially explain a lack of compensation by ALDH1B1 in ALDH2( *)2 individuals. (PMID:23247008)
• Mitochondrial NAD dependent aldehyde dehydrogenase either from yeast or human replaces yeast cytoplasmic NADP dependent aldehyde dehydrogenase for the aerobic growth of yeast on ethanol. (PMID:23454351)
• Telomere lengths in 52 distinct iodine-unstained lesions with reference to both their size and multiplicity, ALDH2 and ADH1B genotypes, and smoking history, were investigated. (PMID:23667679)
• ALDH1 is indicative of stemness and is a biomarker marker in colon cancer. (PMID:24953984)
• Our findings provide clear evidence for both individual and interactive associations of ALDH1b1 and ALDH2 genes with the development of coronary artery disease in Han Chinese. (PMID:25047496)
• ALDH1B1 SNPs play a role in shaping the alcohol drinking patterns among the Inuit in Greenland. (PMID:25311581)
• ALDH1B1 metabolizes nitroglycerin and all-trans-retinaldehyde. One of the three human polymorphisms, ALDH1B1*2, is catalytically inactive, likely due to poor NAD(+) binding. (PMID:25413692)
• Data show that ALDH1B1 may promote colon cancer tumorigenesis by modulating the Wnt/beta-catenin, Notch and PI3K/Akt signaling pathways. (PMID:25950950)
• High expression of ALDH1A2 and ALDH1B1 mRNA was found to be significantly correlated to worser survival in all NSCLC patients. (PMID:26366059)
• ALDH1B1 is expressed at very high levels in human pancreatic cancer, and it contributes to proliferation in these tumor cells. (PMID:26566217)
• The aims of this study were: (i) to use bioinformatic techniques to characterize the possible effects of selected variants in ALDH1B1 on protein structure and function; and, (ii) to genotype three missense and one stop-gain, protein-altering, non-synonymous single nucleotide polymorphisms in 1478 alcohol dependent cases and 1254 controls of matched British and Irish ancestry. (PMID:28594837)
• These results suggest that ALDH1B1 is a novel human colorectal cancer biomarker (PMID:28881356)
• We identified AMI-5, a protein methyltransferase inhibitor, as an Aldh1b1 inducer and showed that it can maintain Aldh1b1 expression in embryonic pancreas explants. This led to a selective reduction in endocrine specification. This effect was due to a downregulation of Ngn3, and it was mediated through Aldh1b1 since the effect was abolished in Aldh1b1 null pancreata. (PMID:30681750)
• Role of aldehyde dehydrogenases, alcohol dehydrogenase 1B genotype, alcohol consumption, and their combination in breast cancer in East-Asian women. (PMID:32300124)
• Aldehyde dehydrogenase 1B1 is a potential marker of colorectal tumors. (PMID:33438176)
• AMBRA1 Negatively Regulates the Function of ALDH1B1, a Cancer Stem Cell Marker, by Controlling Its Ubiquitination. (PMID:34769507)
• Targeting colorectal cancer with small-molecule inhibitors of ALDH1B1. (PMID:35788181)
• Aldehyde Dehydrogenase 1B1 Is Implicated in DNA Damage Response in Human Colorectal Adenocarcinoma. (PMID:35805102)
• Multi-omics profiling reveals cellular pathways and functions regulated by ALDH1B1 in colon cancer cells. (PMID:37716420)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	aldh3a2a	ENSDARG00000028259
danio_rerio	aldh3a2b	ENSDARG00000029381
danio_rerio	aldh9a1b	ENSDARG00000037061
mus_musculus	Aldh1b1	ENSMUSG00000035561
rattus_norvegicus	Aldh1b1	ENSRNOG00000011497
drosophila_melanogaster	CG8665	FBGN0032945
drosophila_melanogaster	CG31075	FBGN0051075
caenorhabditis_elegans		WBGENE00000107
caenorhabditis_elegans		WBGENE00000108
caenorhabditis_elegans		WBGENE00000109

Paralogs (17): ALDH3B1 (ENSG00000006534), ALDH3A2 (ENSG00000072210), ALDH3A1 (ENSG00000108602), ALDH2 (ENSG00000111275), ALDH5A1 (ENSG00000112294), ALDH8A1 (ENSG00000118514), ALDH6A1 (ENSG00000119711), ALDH1A2 (ENSG00000128918), ALDH3B2 (ENSG00000132746), ALDH1L2 (ENSG00000136010), ALDH9A1 (ENSG00000143149), ALDH1L1 (ENSG00000144908), ALDH4A1 (ENSG00000159423), ALDH16A1 (ENSG00000161618), ALDH7A1 (ENSG00000164904), ALDH1A1 (ENSG00000165092), ALDH1A3 (ENSG00000184254)

Protein

Protein identifiers

Aldehyde dehydrogenase X, mitochondrial — P30837 (reviewed: P30837)

Alternative names: Aldehyde dehydrogenase 5, Aldehyde dehydrogenase family 1 member B1

All UniProt accessions (3): A0A0U1RQK9, A0A384MTJ7, P30837

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.

Subunit / interactions. Homotetramer.

Subcellular location. Mitochondrion matrix.

Tissue specificity. Liver, testis and to a lesser extent in brain.

Pathway. Alcohol metabolism; ethanol degradation; acetate from ethanol: step 2/2.

Similarity. Belongs to the aldehyde dehydrogenase family.

RefSeq proteins (1): NP_000683* (*=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 1.2.1.3 — aldehyde dehydrogenase (NAD+) (BRENDA: 46 organisms, 365 substrates, 267 inhibitors, 547 Km, 169 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
NAD+	0.0003–16	121
ACETALDEHYDE	0.0001–80	59
PROPANAL	—	54
BENZALDEHYDE	—	21
HEXANAL	—	15
PROPIONALDEHYDE	0.0028–12	15
PHOSPHONOACETALDEHYDE	0.0032–0.5	13
GLYCOLALDEHYDE	0.005–0.69	10
FORMALDEHYDE	0.031–0.7	7
P-NITROBENZALDEHYDE	—	7
6-DIMETHYLAMINO-2-NAPHTHALDEHYDE	0.0017–0.02	6
BUTANAL	0.0002–0.045	6
METHYLGLYOXAL	0.0086–1.876	6
NADP+	0.27–8.47	6
OCTANAL	—	6

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (72 total): strand 22, helix 20, modified residue 15, sequence variant 4, turn 3, active site 2, sequence conflict 2, transit peptide 1, chain 1, binding site 1, site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7MJD	X-RAY DIFFRACTION	2.12
7RAD	X-RAY DIFFRACTION	2.3
7MJC	X-RAY DIFFRACTION	2.68

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30837-F1	95.49	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): 285 (proton acceptor); 319 (nucleophile); 186 (transition state stabilizer)

Ligand- & substrate-binding residues (1): 262–267

Post-translational modifications (15): 364, 364, 383, 383, 399, 399, 414, 414, 426, 426, 429, 51, 52, 52, 81

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-71384	Ethanol oxidation
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-1430728	Metabolism
R-HSA-211859	Biological oxidations
R-HSA-211945	Phase I - Functionalization of compounds
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 199 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MODULE_255, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION, KEGG_HISTIDINE_METABOLISM, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, chr9p13, MODULE_480, DELYS_THYROID_CANCER_DN, VANHARANTA_UTERINE_FIBROID_WITH_7Q_DELETION_DN, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, KEGG_LYSINE_DEGRADATION

GO Biological Process (3): carbohydrate metabolic process (GO:0005975), ethanol catabolic process (GO:0006068), aldehyde metabolic process (GO:0006081)

GO Molecular Function (4): aldehyde dehydrogenase (NAD+) activity (GO:0004029), NAD binding (GO:0051287), 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 (4): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Phase I - Functionalization of compounds	1
Metabolism of proteins	1
Metabolism	1
Biological oxidations	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
primary metabolic process	1
ethanol metabolic process	1
primary alcohol catabolic process	1
metabolic process	1
aldehyde dehydrogenase [NAD(P)+] activity	1
adenyl nucleotide binding	1
catalytic activity	1
oxidoreductase activity, acting on the aldehyde or oxo group of donors	1
nuclear lumen	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

3323 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALDH1B1	ALDH18A1	P54886	646
ALDH1B1	ADH1B	P00325	608
ALDH1B1	ADH1C	P00326	605
ALDH1B1	ADH6	P28332	602
ALDH1B1	ADH7	P40394	571
ALDH1B1	ESD	P10768	562
ALDH1B1	AKR1B1	P15121	540
ALDH1B1	ADH1A	P07327	539
ALDH1B1	ADH5	P11766	539
ALDH1B1	ADH4	P08319	539
ALDH1B1	ABCC6	P78420	512
ALDH1B1	H7C2H4	H7C2H4	486
ALDH1B1	P0DN79	P0DN79	486
ALDH1B1	MUC1	P13931	478
ALDH1B1	CNBP	P20694	467

IntAct

82 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
ALDH1B1	DHRS4	psi-mi:“MI:0914”(association)	0.530
PITPNM3	ALDH1B1	psi-mi:“MI:0915”(physical association)	0.400
ZNF341	ALDH1B1	psi-mi:“MI:0915”(physical association)	0.400
COL6A6	ALDH1B1	psi-mi:“MI:0915”(physical association)	0.400
CHLSN	ALDH1B1	psi-mi:“MI:0915”(physical association)	0.400
TOP1	ALDH1B1	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
ALDH1B1	FABP2	psi-mi:“MI:0915”(physical association)	0.370
Bub1	PEX10	psi-mi:“MI:0914”(association)	0.350
SGO1	ELOC	psi-mi:“MI:0914”(association)	0.350
Bag2		psi-mi:“MI:0914”(association)	0.350
Tubg1	RTL8C	psi-mi:“MI:0914”(association)	0.350
ATL3	SNX14	psi-mi:“MI:0914”(association)	0.350
Lgals3bp	CS	psi-mi:“MI:0914”(association)	0.350
HDAC1	TRAK1	psi-mi:“MI:0914”(association)	0.350
LLGL1	ALDH1B1	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
MYC	ILVBL	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (234): FEM1B (Affinity Capture-MS), SUFU (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), ALDH1B1 (Affinity Capture-MS), ALDH1B1 (Co-fractionation), ALDH1B1 (Co-fractionation), ALDH1B1 (Co-fractionation), ALDH1B1 (Co-fractionation), ALDH1B1 (Co-fractionation), ALDH1B1 (Co-fractionation), ALDH1B1 (Co-fractionation), ALDH1B1 (Co-fractionation), ALDH1B1 (Co-fractionation), ALDH1B1 (Co-fractionation), ESD (Co-fractionation)

ESM2 similar proteins: A0A2I7G3B0, A6ZR27, C5I9X1, C7A2A0, O14293, O35945, O74187, P00352, P05091, P08157, P11884, P12762, P13601, P15437, P17202, P20000, P24549, P30837, P30841, P40047, P40108, P41751, P42041, P42757, P46367, P47738, P47771, P48644, P51647, P51977, P54114, P54115, P81178, P86886, Q25417, Q27640, Q28399, Q29490, Q2XQV4, Q5R6B5

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 104 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
autophagosome maturation	5	19.3×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	2
Uncertain significance	65
Likely benign	5
Benign	12

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1210151	GRCh37/hg19 9p13.2-13.1(chr9:36426622-38787479)x1	Pathogenic
1210152	GRCh37/hg19 9p13.2-13.1(chr9:36442195-39156958)x1	Pathogenic
144347	GRCh38/hg38 9p13.3-13.1(chr9:33225730-38529813)x3	Pathogenic
144556	GRCh38/hg38 9p13.3-13.1(chr9:35623500-38815474)x3	Pathogenic
3242301	GRCh37/hg19 9p13.3-13.1(chr9:35495055-39184042)x1	Pathogenic
57406	GRCh38/hg38 9p24.3-13.1(chr9:204193-38741440)x3	Pathogenic
689135	GRCh37/hg19 9p13.3-q13(chr9:34542635-68210033)x3	Pathogenic
815190	GRCh37/hg19 9p24.3-q21.11(chr9:203861-70984588)x3	Pathogenic
214113	NM_000692.5(ALDH1B1):c.764T>C (p.Val255Ala)	Likely pathogenic
3063115	GRCh37/hg19 9p13.3-13.1(chr9:35440393-38787480)x1	Likely pathogenic

SpliceAI

215 predictions. Top by Δscore:

Variant	Effect	Δscore
9:38392805:CAGGT:C	donor_loss	1.0000
9:38392806:AGG:A	donor_loss	1.0000
9:38392808:GTA:G	donor_loss	1.0000
9:38395738:A:AG	acceptor_gain	1.0000
9:38395739:G:GG	acceptor_gain	1.0000
9:38395739:GA:G	acceptor_gain	1.0000
9:38395739:GAGT:G	acceptor_gain	1.0000
9:38392804:GCAG:G	donor_gain	0.9900
9:38392808:G:GG	donor_gain	0.9900
9:38392809:T:A	donor_loss	0.9900
9:38395727:T:TA	acceptor_gain	0.9900
9:38395735:TCCAG:T	acceptor_gain	0.9900
9:38395736:CCAG:C	acceptor_gain	0.9900
9:38395737:CAG:C	acceptor_gain	0.9900
9:38395737:CAGAG:C	acceptor_gain	0.9900
9:38395738:A:C	acceptor_loss	0.9900
9:38395738:AGA:A	acceptor_gain	0.9900
9:38395738:AGAGT:A	acceptor_gain	0.9900
9:38395739:G:T	acceptor_gain	0.9900
9:38395739:GAGTG:G	acceptor_gain	0.9900
9:38395736:CCAGA:C	acceptor_gain	0.9700
9:38395738:AGAG:A	acceptor_gain	0.9700
9:38394564:GC:G	donor_gain	0.9600
9:38394633:GAT:G	donor_gain	0.9200
9:38395727:T:A	acceptor_loss	0.8900
9:38392805:C:T	donor_gain	0.8800
9:38394566:G:GG	donor_gain	0.8800
9:38394635:T:TG	donor_gain	0.8700
9:38395734:CTCCA:C	acceptor_gain	0.8700
9:38394635:T:G	donor_gain	0.8200

AlphaMissense

3383 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:38396306:C:A	N186K	0.999
9:38396306:C:G	N186K	0.999
9:38396301:T:A	W185R	0.998
9:38396301:T:C	W185R	0.998
9:38396307:T:C	F187L	0.998
9:38396309:C:A	F187L	0.998
9:38396309:C:G	F187L	0.998
9:38397000:T:C	F418L	0.998
9:38397002:T:A	F418L	0.998
9:38397002:T:G	F418L	0.998
9:38397192:T:C	F482L	0.998
9:38397194:T:A	F482L	0.998
9:38397194:T:G	F482L	0.998
9:38397144:G:T	G466W	0.997
9:38396304:A:C	N186H	0.996
9:38396304:A:G	N186D	0.996
9:38396526:T:C	F260L	0.996
9:38396528:C:A	F260L	0.996
9:38396528:C:G	F260L	0.996
9:38396616:A:C	S290R	0.996
9:38396618:C:A	S290R	0.996
9:38396618:C:G	S290R	0.996
9:38396695:G:A	G316D	0.996
9:38396695:G:T	G316V	0.996
9:38396719:G:C	R324P	0.996
9:38397084:G:C	A446P	0.996
9:38397196:G:A	G483E	0.996
9:38396025:T:A	W93R	0.995
9:38396025:T:C	W93R	0.995
9:38396130:G:T	G128W	0.995

dbSNP variants (sampled 300 via entrez): RS1000614162 (9:38391156 G>T), RS1000702909 (9:38395615 T>A), RS1001624753 (9:38391867 A>G), RS1001643120 (9:38390937 A>C), RS1001664325 (9:38391435 C>A,T), RS1002076225 (9:38390754 C>G), RS1002348391 (9:38396437 T>G), RS1003162730 (9:38397836 C>A), RS1003314235 (9:38393575 C>A), RS1004215748 (9:38399103 G>A,T), RS1004320698 (9:38394880 C>A,T), RS1004578490 (9:38391819 C>A), RS1004643833 (9:38393214 G>A), RS1005244085 (9:38395982 G>T), RS1005370310 (9:38390832 C>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (2): neurodevelopmental disorder (MONDO:0700092), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (1): Non-specific syndromic intellectual disability (Orphanet:528084)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004125_12	Type 2 diabetes (age of onset)	4.000000e-06
GCST007096_135	Pulse pressure	7.000000e-09
GCST007097_64	Pulse pressure	4.000000e-06
GCST007099_140	Systolic blood pressure	3.000000e-06
GCST007327_149	Smoking status (ever vs never smokers)	5.000000e-09
GCST008476_8	Emphysema annual change measurement in smokers (percent low attenuation area)	4.000000e-06
GCST009391_36	Metabolite levels	4.000000e-06
GCST009799_3	Alcohol consumption (drinkers vs non-drinkers)	3.000000e-19
GCST012276_11	Clostridioides difficle infection in antibiotics-users	5.000000e-06
GCST012419_2	Longevity (100 years and older)	2.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0004318	smoking behavior
EFO:0007626	emphysema imaging measurement
EFO:0010116	choline measurement
EFO:0004329	alcohol drinking
EFO:0009130	clostridium difficile infection

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3542434 (PROTEIN FAMILY), CHEMBL4881 (SINGLE PROTEIN)

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

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2073478	ALDH1B1		0.00	0
rs2228093	ALDH1B1		0.00	0
rs4878199	ALDH1B1		0.00	0
rs142427338	ALDH1B1		0.00	0

ChEMBL bioactivities

14 potent at pChembl≥5 of 15 total, top 13 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.14	Kd	7.196	nM	CHEMBL5653589
8.14	ED50	7.196	nM	CHEMBL5653589
8.03	Kd	9.432	nM	CHEMBL3752910
8.03	ED50	9.432	nM	CHEMBL3752910
7.52	IC50	30	nM	CHEMBL5723324
7.07	IC50	86	nM	CHEMBL1562069
7.02	IC50	95	nM	CHEMBL4090473
6.80	IC50	160	nM	CHEMBL1349972
6.51	IC50	310	nM	CHEMBL4072941
6.44	IC50	360	nM	CHEMBL4099822
6.06	IC50	880	nM	CHEMBL4064364
5.58	IC50	2600	nM	CHEMBL1335126
5.29	IC50	5100	nM	DAIDZIN

PubChem BioAssay actives

11 with measured affinity, of 84 total; 10 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147841: Binding affinity to human ALDH1B1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0072	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147841: Binding affinity to human ALDH1B1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0094	uM
2,3-dimethyl-5-propylfuro[3,2-g]chromen-7-one	1441739: Inhibition of full length recombinant human ALDH1B1 expressed in Escherichia coli TunerDE3 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	0.0860	uM
9,10-dimethyl-1,2,3,4-tetrahydro-[1]benzofuro[6,5-c]isochromen-5-one	1441739: Inhibition of full length recombinant human ALDH1B1 expressed in Escherichia coli TunerDE3 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	0.0950	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	1441739: Inhibition of full length recombinant human ALDH1B1 expressed in Escherichia coli TunerDE3 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	0.1600	uM
2,3,5,6-tetramethylfuro[3,2-g]chromen-7-one	1441739: Inhibition of full length recombinant human ALDH1B1 expressed in Escherichia coli TunerDE3 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	0.3100	uM
2,3,5-trimethyl-6-propylfuro[3,2-g]chromen-7-one	1441739: Inhibition of full length recombinant human ALDH1B1 expressed in Escherichia coli TunerDE3 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	0.3600	uM
3,5-dimethyl-6-propylfuro[3,2-g]chromen-7-one	1441739: Inhibition of full length recombinant human ALDH1B1 expressed in Escherichia coli TunerDE3 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	0.8800	uM
2,3,5-trimethyl-6-(3-oxo-3-piperidin-1-ylpropyl)furo[3,2-g]chromen-7-one	1441739: Inhibition of full length recombinant human ALDH1B1 expressed in Escherichia coli TunerDE3 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	2.6000	uM
3-(4-hydroxyphenyl)-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one	1441739: Inhibition of full length recombinant human ALDH1B1 expressed in Escherichia coli TunerDE3 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	5.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	increases expression	5
Valproic Acid	affects expression, decreases expression, increases expression	4
bisphenol A	decreases expression, increases expression	3
Cyclosporine	decreases expression	3
cobaltous chloride	decreases expression	2
entinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Acetaminophen	decreases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
testosterone enanthate	affects expression	1
apocarotenal	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	affects cotreatment, increases metabolic processing	1
perfosfamide	affects response to substance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
zinc chromate	increases abundance, decreases expression	1
manganese chloride	increases abundance, increases expression	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1

ChEMBL screening assays

16 unique, capped per target: 15 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1019416	Binding	Effect on human recombinant his-tagged mitochondrial ALDH5 activity expressed in Escherichia coli BL21 cells at 100 uM	Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. — Science
CHEMBL5723253	Functional	Affinity Biochemical interaction: (inhibition of enzyme activity with DH fluorescence as readout) EUB0002600aFA ALDH1B1	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8HA	Ubigene HCT 116 ALDH1B1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism