ALDH9A1

Summary

ALDH9A1 (aldehyde dehydrogenase 9 family member A1, HGNC:412) is a protein-coding gene on chromosome 1q24.1, encoding 4-trimethylaminobutyraldehyde dehydrogenase (P49189). Converts gamma-trimethylaminobutyraldehyde into gamma-butyrobetaine with high efficiency (in vitro).

This protein belongs to the aldehyde dehydrogenase family of proteins. It has a high activity for oxidation of gamma-aminobutyraldehyde and other amino aldehydes. The enzyme catalyzes the dehydrogenation of gamma-aminobutyraldehyde to gamma-aminobutyric acid (GABA). This isozyme is a tetramer of identical 54-kD subunits.

Source: NCBI Gene 223 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 93 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_000696

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:412
Approved symbol	ALDH9A1
Name	aldehyde dehydrogenase 9 family member A1
Location	1q24.1
Locus type	gene with protein product
Status	Approved
Aliases	E3
Ensembl gene	ENSG00000143149
Ensembl biotype	protein_coding
OMIM	602733
Entrez	223

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000354775, ENST00000461664, ENST00000463610, ENST00000471457, ENST00000491436, ENST00000865474, ENST00000865475, ENST00000865476, ENST00000923581

RefSeq mRNA: 2 — MANE Select: NM_000696 NM_000696, NM_001365774

CCDS: CCDS1250

Canonical transcript exons

ENST00000354775 — 11 exons

Exon	Start	End
ENSE00000958358	165698378	165698562
ENSE00000958365	165668926	165669013
ENSE00000958366	165667309	165667450
ENSE00000958367	165665018	165665130
ENSE00000958368	165662216	165663144
ENSE00003467443	165695252	165695397
ENSE00003541963	165679442	165679582
ENSE00003603928	165682981	165683110
ENSE00003626215	165680487	165680683
ENSE00003633692	165669262	165669450
ENSE00003690245	165682107	165682241

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.7337 / max 508.0769, expressed in 1822 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15734	23.7368	1819
15735	12.7851	1805
15733	3.2118	1439

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	98.39	gold quality
right adrenal gland	UBERON:0001233	98.36	gold quality
left adrenal gland	UBERON:0001234	97.99	gold quality
left adrenal gland cortex	UBERON:0035825	97.80	gold quality
adrenal gland	UBERON:0002369	97.77	gold quality
saliva-secreting gland	UBERON:0001044	97.58	gold quality
minor salivary gland	UBERON:0001830	97.53	gold quality
esophagus mucosa	UBERON:0002469	97.52	gold quality
adrenal tissue	UBERON:0018303	97.37	gold quality
left lobe of thyroid gland	UBERON:0001120	97.05	gold quality
thyroid gland	UBERON:0002046	97.01	gold quality
right lobe of thyroid gland	UBERON:0001119	96.94	gold quality
liver	UBERON:0002107	96.62	gold quality
corpus callosum	UBERON:0002336	96.58	gold quality
thoracic mammary gland	UBERON:0005200	96.44	gold quality
right lobe of liver	UBERON:0001114	96.41	gold quality
islet of Langerhans	UBERON:0000006	96.25	gold quality
skin of abdomen	UBERON:0001416	96.13	gold quality
zone of skin	UBERON:0000014	96.10	gold quality
tonsil	UBERON:0002372	96.08	gold quality
skin of leg	UBERON:0001511	96.06	gold quality
adult mammalian kidney	UBERON:0000082	96.05	gold quality
ventricular zone	UBERON:0003053	96.03	gold quality
amygdala	UBERON:0001876	96.01	gold quality
temporal lobe	UBERON:0001871	95.91	gold quality
rectum	UBERON:0001052	95.89	gold quality
adipose tissue	UBERON:0001013	95.77	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.76	gold quality
duodenum	UBERON:0002114	95.74	gold quality
omental fat pad	UBERON:0010414	95.70	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.69
E-MTAB-10290	no	113.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

51 targeting ALDH9A1, 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-4262	100.00	73.26	3931
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-4784	99.15	67.41	1733

Literature-anchored findings (GeneRIF, showing 3)

• TMABA-DH colocalized with myosin light chains in cardiac myocytes. (PMID:26010099)
• structural comparison reveals a position and a fold of the inter-domain linker of ALDH9A1 never observed in any other ALDH so far. (PMID:30914451)
• N6-methyladenosine-modified ALDH9A1 modulates lipid accumulation and tumor progression in clear cell renal cell carcinoma through the NPM1/IQGAP2/AKT signaling pathway. (PMID:39039052)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	aldh9a1a.2	ENSDARG00000055331
danio_rerio	aldh9a1a.1	ENSDARG00000069100
mus_musculus	Aldh9a1	ENSMUSG00000026687
rattus_norvegicus	Aldh9a1	ENSRNOG00000004027
drosophila_melanogaster	CG8665	FBGN0032945
drosophila_melanogaster	CG31075	FBGN0051075
caenorhabditis_elegans		WBGENE00000107
caenorhabditis_elegans		WBGENE00000108
caenorhabditis_elegans		WBGENE00000109
caenorhabditis_elegans		WBGENE00000117

Paralogs (17): ALDH3B1 (ENSG00000006534), ALDH3A2 (ENSG00000072210), ALDH3A1 (ENSG00000108602), ALDH2 (ENSG00000111275), ALDH5A1 (ENSG00000112294), ALDH8A1 (ENSG00000118514), ALDH6A1 (ENSG00000119711), ALDH1A2 (ENSG00000128918), ALDH3B2 (ENSG00000132746), ALDH1L2 (ENSG00000136010), ALDH1B1 (ENSG00000137124), ALDH1L1 (ENSG00000144908), ALDH4A1 (ENSG00000159423), ALDH16A1 (ENSG00000161618), ALDH7A1 (ENSG00000164904), ALDH1A1 (ENSG00000165092), ALDH1A3 (ENSG00000184254)

Protein

Protein identifiers

4-trimethylaminobutyraldehyde dehydrogenase — P49189 (reviewed: P49189)

Alternative names: Aldehyde dehydrogenase E3 isozyme, Aldehyde dehydrogenase family 9 member A1, Formaldehyde dehydrogenase, Gamma-aminobutyraldehyde dehydrogenase, R-aminobutyraldehyde dehydrogenase

All UniProt accessions (2): P49189, B4DX14

UniProt curated annotations — full annotation on UniProt →

Function. Converts gamma-trimethylaminobutyraldehyde into gamma-butyrobetaine with high efficiency (in vitro). Can catalyze the irreversible oxidation of a broad range of aldehydes to the corresponding acids in an NAD-dependent reaction, but with low efficiency. Catalyzes the oxidation of aldehydes arising from biogenic amines and polyamines.

Subunit / interactions. Homotetramer.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Detected in brain (at protein level). High expression in adult liver, skeletal muscle, and kidney. Low levels in heart, pancreas, lung and brain. Expressed in all regions of the brain. Expression levels are variable in the different brain areas, with the highest levels in the spinal cord and the lowest in the occipital pole.

Pathway. Amine and polyamine biosynthesis; carnitine biosynthesis.

Miscellaneous. Produced by alternative splicing. Produced by alternative initiation. Contains a predicted signal peptide at positions 1-24.

Similarity. Belongs to the aldehyde dehydrogenase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P49189-1	1	yes
P49189-2	2
P49189-3	3

RefSeq proteins (2): NP_000687, NP_001352703 (=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 1.2.1.47 — 4-trimethylammoniobutyraldehyde dehydrogenase (BRENDA: 5 organisms, 46 substrates, 44 inhibitors, 36 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
NAD+	0.028–1.16	4
4-AMINOBUTYRALDEHYDE	0.024–0.067	2
4-DIMETHYLAMINOBUTYRALDEHYDE	0.051–0.62	2
4-N-TRIMETHYLAMINOBUTYRALDEHYDE	0.0074–0.31	2
4-TRIMETHYLAMINOBUTYRALDEHYDE	0.0014–0.0042	2
ACETALDEHYDE	0.017–0.102	2
BUTYRALDEHYDE	0.013–0.216	2
HEXANAL	0.009–0.05	2
2-HEXENAL	0.026	1
3,4-DIHYDROXYPHENYLACETALDEHYDE	0.011	1
3-AMINOPROPIONALDEHYDE	0.056	1
4-(DIMETHYLAMINO)BUTYRALDEHYDE	0.021	1
4-(TRIMETHYLAMINO)BUTYRALDEHYDE	0.006	1
4-GUANIDINOBUTYRALDEHYDE	0.021	1
BETAINE ALDEHYDE	0.123	1

Catalyzed reactions (Rhea), 12 shown:

• an aldehyde + NAD(+) + H2O = a carboxylate + NADH + 2 H(+) (RHEA:16185)
• formaldehyde + NAD(+) + H2O = formate + NADH + 2 H(+) (RHEA:16425)
• 4-(trimethylamino)butanal + NAD(+) + H2O = 4-(trimethylamino)butanoate + NADH + 2 H(+) (RHEA:17985)
• 4-aminobutanal + NAD(+) + H2O = 4-aminobutanoate + NADH + 2 H(+) (RHEA:19105)
• acetaldehyde + NAD(+) + H2O = acetate + NADH + 2 H(+) (RHEA:25294)
• imidazole-4-acetaldehyde + NAD(+) + H2O = imidazole-4-acetate + NADH + 2 H(+) (RHEA:31059)
• (5-hydroxyindol-3-yl)acetaldehyde + NAD(+) + H2O = (5-hydroxyindol-3-yl)acetate + NADH + 2 H(+) (RHEA:31215)
• propanal + NAD(+) + H2O = propanoate + NADH + 2 H(+) (RHEA:67256)
• hexanal + NAD(+) + H2O = hexanoate + NADH + 2 H(+) (RHEA:67276)
• 3,4-dihydroxyphenylacetaldehyde + NAD(+) + H2O = 3,4-dihydroxyphenylacetate + NADH + 2 H(+) (RHEA:69080)
• acrolein + NAD(+) + H2O = acrylate + NADH + 2 H(+) (RHEA:69084)
• butanal + NAD(+) + H2O = butanoate + NADH + 2 H(+) (RHEA:69088)

UniProt features (69 total): strand 22, helix 20, modified residue 8, sequence conflict 4, turn 3, binding site 3, chain 2, splice variant 2, active site 2, initiator methionine 1, sequence variant 1, site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6QAP	X-RAY DIFFRACTION	2.3
6QAK	X-RAY DIFFRACTION	2.5
6VR6	X-RAY DIFFRACTION	2.5
6VWF	X-RAY DIFFRACTION	2.64
6QAO	X-RAY DIFFRACTION	2.89

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49189-F1	98.31	1.00

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): 254 (proton acceptor); 288 (nucleophile); 157 (transition state stabilizer)

Ligand- & substrate-binding residues (3): 180; 232–236; 391

Post-translational modifications (8): 30, 30, 59, 298, 303, 303, 344, 2

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-71262	Carnitine synthesis
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 221 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, MODULE_93, HNF3ALPHA_Q6, GOBP_PROTEIN_HOMOTETRAMERIZATION, MODULE_151, KYNG_DNA_DAMAGE_DN, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION, GTGCCTT_MIR506, KEGG_HISTIDINE_METABOLISM, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_CIS, HFH4_01, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, KEGG_LYSINE_DEGRADATION

GO Biological Process (4): aldehyde metabolic process (GO:0006081), serotonin catabolic process (GO:0042429), carnitine biosynthetic process (GO:0045329), protein homotetramerization (GO:0051289)

GO Molecular Function (8): aldehyde dehydrogenase (NAD+) activity (GO:0004029), formaldehyde dehydrogenase (NAD+) activity (GO:0018467), aminobutyraldehyde dehydrogenase (NAD+) activity (GO:0019145), small molecule binding (GO:0036094), 4-trimethylammoniobutyraldehyde dehydrogenase activity (GO:0047105), acetaldehyde dehydrogenase (NAD+) activity (GO:0140087), 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): cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
aldehyde dehydrogenase (NAD+) activity	3
cellular anatomical structure	2
cytoplasm	2
metabolic process	1
phenol-containing compound catabolic process	1
serotonin metabolic process	1
indole-containing compound catabolic process	1
primary amino compound catabolic process	1
amino-acid betaine biosynthetic process	1
carnitine metabolic process	1
protein homooligomerization	1
protein tetramerization	1
aldehyde dehydrogenase [NAD(P)+] activity	1
binding	1
oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor	1
catalytic activity	1
oxidoreductase activity, acting on the aldehyde or oxo group of donors	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1

Protein interactions and networks

STRING

3664 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALDH9A1	NDUFS8	O00217	759
ALDH9A1	ALDH18A1	P54886	617
ALDH9A1	TMLHE	Q9NVH6	610
ALDH9A1	ADH6	P28332	572
ALDH9A1	HADHB	P55084	542
ALDH9A1	ADH7	P40394	538
ALDH9A1	ADH1A	P07327	510
ALDH9A1	ADH5	P11766	503
ALDH9A1	ADH4	P08319	484
ALDH9A1	ADH1C	P00326	483
ALDH9A1	BBOX1	O75936	457
ALDH9A1	ADH1B	P00325	457
ALDH9A1	ACAA1	P09110	452
ALDH9A1	SLC22A5	O76082	451
ALDH9A1	DLAT	P10515	433

IntAct

18 interactions, top by confidence:

A	B	Type	Score
CUL4B	APBB1	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
TNIP3	RNH1	psi-mi:“MI:0914”(association)	0.350
USP46	PJA2	psi-mi:“MI:0914”(association)	0.350
ARID5A	ALDH9A1	psi-mi:“MI:0914”(association)	0.350
ORF4a	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
GABARAPL1		psi-mi:“MI:0914”(association)	0.350
DDA1	PGK1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
FECH	GTPBP10	psi-mi:“MI:0914”(association)	0.350
PLGRKT	PGRMC1	psi-mi:“MI:2364”(proximity)	0.270
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HLA-B	ALDH9A1	psi-mi:“MI:0915”(physical association)	0.000
ALDH9A1	flgH1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (100): ALDH9A1 (Affinity Capture-MS), ALDH9A1 (Affinity Capture-MS), ALDH9A1 (Affinity Capture-MS), ALDH9A1 (Affinity Capture-MS), ALDH9A1 (Proximity Label-MS), ALDH9A1 (Affinity Capture-MS), ALDH9A1 (Co-fractionation), ALDH9A1 (Co-fractionation), PGD (Co-fractionation), ALDH9A1 (Co-fractionation), DIABLO (Co-fractionation), ALDH9A1 (Co-fractionation), YWHAZ (Co-fractionation), DNAJC5 (Co-fractionation), ALDH9A1 (Co-fractionation)

ESM2 similar proteins: B9F3B6, C7A2A0, O35945, P00352, P05091, P11884, P13601, P15437, P20000, P24549, P30837, P42757, P47738, P48644, P49189, P51647, P51649, P51650, P51977, P56533, P81178, P86886, Q02253, Q07536, Q19A30, Q25417, Q28399, Q29228, Q29490, Q2KJH9, Q2XQV4, Q3MSM3, Q3MSM4, Q5R6B5, Q5R8A4, Q5RF00, Q62148, Q6A2H0, Q6A2H1, Q6A2H2

Diamond homologs: A0A2I7G3B0, A0B2F6, A0PN13, A0QMB9, A1KF54, A1UVS4, A2RWD6, A3MEC6, A3P6B0, A3PI00, A4WUY6, A5TYV9, A5VPA5, A6VEI4, A6W2P7, A6X2G8, A7FKL5, A9AN00, A9M9H7, B0CKN3, B1K708, B1Z033, B2SA42, B3PTE1, B4EHJ1, B5ZUG3, B9F3B6, B9JBA3, B9KNS6, C0RHQ3, C3MIE5, E1V7V8, O04895, O14293, O32507, O34660, O69497, O93344, O94788, P05091

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ALDH9A1	“down-regulates quantity”	4-trimethylammoniobutanal	“chemical modification”
ALDH9A1	“up-regulates quantity”	4-(trimethylammonio)butanoate	“chemical modification”
ALDH9A1	“down-regulates quantity”	NAD(1-)	“chemical modification”
ALDH9A1	“up-regulates quantity”	NADH(2-)	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	71
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
60043	GRCh38/hg38 1q23.3-24.2(chr1:162040050-167480663)x1	Pathogenic

SpliceAI

1769 predictions. Top by Δscore:

Variant	Effect	Δscore
1:165665013:CTCA:C	donor_loss	1.0000
1:165665015:CAC:C	donor_loss	1.0000
1:165665017:CCTGA:C	donor_gain	1.0000
1:165665126:TGTCC:T	acceptor_gain	1.0000
1:165665128:TCCC:T	acceptor_loss	1.0000
1:165665129:CC:C	acceptor_gain	1.0000
1:165665130:CC:C	acceptor_gain	1.0000
1:165665130:CCT:C	acceptor_loss	1.0000
1:165665131:C:CC	acceptor_gain	1.0000
1:165665131:CTAT:C	acceptor_loss	1.0000
1:165665132:T:C	acceptor_loss	1.0000
1:165665133:A:C	acceptor_gain	1.0000
1:165667304:CATA:C	donor_loss	1.0000
1:165667305:ATAC:A	donor_loss	1.0000
1:165667306:TA:T	donor_loss	1.0000
1:165667308:C:CT	donor_loss	1.0000
1:165667447:TTAG:T	acceptor_gain	1.0000
1:165667448:TAG:T	acceptor_gain	1.0000
1:165667451:C:CC	acceptor_gain	1.0000
1:165668924:A:AC	donor_gain	1.0000
1:165668925:C:CC	donor_gain	1.0000
1:165668928:A:AC	donor_gain	1.0000
1:165668929:A:C	donor_gain	1.0000
1:165668955:T:TA	donor_gain	1.0000
1:165669260:A:AC	donor_gain	1.0000
1:165669261:C:CC	donor_gain	1.0000
1:165669261:CCTG:C	donor_gain	1.0000
1:165669446:CAAAC:C	acceptor_gain	1.0000
1:165669448:AAC:A	acceptor_gain	1.0000
1:165669449:ACCTA:A	acceptor_loss	1.0000

AlphaMissense

3372 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000060334 (1:165678057 C>A,T), RS1000119601 (1:165673784 G>C), RS1000120369 (1:165690444 T>C), RS1000264215 (1:165675062 G>T), RS1000494314 (1:165690171 A>G), RS1000526836 (1:165669475 A>C,G), RS1000623858 (1:165685714 G>A), RS1000794189 (1:165668012 T>C), RS1000869576 (1:165699175 G>T), RS1000935067 (1:165691386 C>T), RS1001007804 (1:165691575 T>A,C), RS1001088986 (1:165691153 G>C), RS1001100739 (1:165691305 T>C), RS1001121397 (1:165675153 T>G), RS1001179829 (1:165679544 G>A)

Disease associations

OMIM: gene MIM:602733 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_397	Refractive error	9.000000e-48

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2542 (SINGLE PROTEIN), CHEMBL3542434 (PROTEIN FAMILY)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — GABA turnover

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	4
bisphenol F	affects cotreatment, increases methylation, increases expression	2
bisphenol A	decreases expression, increases expression	2
Resveratrol	increases expression, affects cotreatment	2
Cadmium Chloride	increases abundance, increases expression	2
Particulate Matter	increases abundance, affects cotreatment, decreases expression	2
triphenyl phosphate	affects expression	1
4-aminobutyraldehyde	increases metabolic processing	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
arsenite	affects binding, increases reaction	1
perfluorooctanoic acid	increases expression	1
isobutyl alcohol	decreases expression, increases abundance, affects cotreatment	1
n-butoxyacetaldehyde	increases oxidation	1
fenpyroximate	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
bisphenol B	increases expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
LDN 193189	increases expression, affects cotreatment	1
picoxystrobin	decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaldehyde	increases oxidation	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arecoline	decreases expression	1
Benzo(a)pyrene	affects cotreatment, decreases expression	1
Cadmium	increases abundance, increases expression	1
Cannabidiol	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5108430	Binding	Binding affinity to ALDH9A1 in human HEK293 cells assessed as fold change at 130 nM incubated for 3 to 6 hrs by LFQ-chemical proteomics analysis	Activity-based protein profiling reveals deubiquitinase and aldehyde dehydrogenase targets of a cyanopyrrolidine probe. — RSC Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2RH	Abcam HEK293T ALDH9A1 KO	Transformed cell line	Female
CVCL_SC23	HAP1 ALDH9A1 (-) 1	Cancer cell line	Male
CVCL_XL26	HAP1 ALDH9A1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer