ALDH7A1

Summary

ALDH7A1 (aldehyde dehydrogenase 7 family member A1, HGNC:877) is a protein-coding gene on chromosome 5q23.2, encoding Alpha-aminoadipic semialdehyde dehydrogenase (P49419). Aldehyde dehydrogenase enzyme that mediates important protective effects.

The protein encoded by this gene is a member of subfamily 7 in the aldehyde dehydrogenase gene family. These enzymes are thought to play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. This particular member has homology to a previously described protein from the green garden pea, the 26g pea turgor protein. It is also involved in lysine catabolism that is known to occur in the mitochondrial matrix. Recent reports show that this protein is found both in the cytosol and the mitochondria, and the two forms likely arise from the use of alternative translation initiation sites. An additional variant encoding a different isoform has also been found for this gene. Mutations in this gene are associated with pyridoxine-dependent epilepsy. Several related pseudogenes have also been identified.

Source: NCBI Gene 501 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pyridoxine-dependent epilepsy (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 1,205 total — 110 pathogenic, 67 likely-pathogenic
• Phenotypes (HPO): 47
• Druggable target: yes
• MANE Select transcript: NM_001182

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:877
Approved symbol	ALDH7A1
Name	aldehyde dehydrogenase 7 family member A1
Location	5q23.2
Locus type	gene with protein product
Status	Approved
Aliases	EPD, PDE
Ensembl gene	ENSG00000164904
Ensembl biotype	protein_coding
OMIM	107323
Entrez	501

Gene structure

Transcript identifiers

Ensembl transcripts: 56 — 32 protein_coding, 12 retained_intron, 9 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000409134, ENST00000412186, ENST00000413020, ENST00000433026, ENST00000458249, ENST00000476328, ENST00000479989, ENST00000485852, ENST00000497231, ENST00000503281, ENST00000509270, ENST00000509459, ENST00000510111, ENST00000511266, ENST00000553117, ENST00000635851, ENST00000635858, ENST00000635933, ENST00000636062, ENST00000636190, ENST00000636225, ENST00000636286, ENST00000636482, ENST00000636743, ENST00000636808, ENST00000636872, ENST00000636879, ENST00000636886, ENST00000636892, ENST00000637070, ENST00000637206, ENST00000637272, ENST00000637292, ENST00000637782, ENST00000637964, ENST00000638008, ENST00000638010, ENST00000865287, ENST00000865288, ENST00000865289, ENST00000865290, ENST00000865291, ENST00000865292, ENST00000865293, ENST00000865294, ENST00000865295, ENST00000865296, ENST00000865297, ENST00000865298, ENST00000939100, ENST00000939101, ENST00000939102, ENST00000939103, ENST00000939104, ENST00000939105, ENST00000960036

RefSeq mRNA: 3 — MANE Select: NM_001182 NM_001182, NM_001201377, NM_001202404

CCDS: CCDS4137, CCDS56380

Canonical transcript exons

ENST00000409134 — 18 exons

Exon	Start	End
ENSE00001584033	126541841	126545019
ENSE00002067069	126595007	126595219
ENSE00003458640	126550196	126550293
ENSE00003476482	126577079	126577211
ENSE00003508209	126561083	126561124
ENSE00003515832	126552021	126552137
ENSE00003530035	126570782	126570859
ENSE00003535192	126555931	126556015
ENSE00003565049	126592664	126592729
ENSE00003592629	126559240	126559334
ENSE00003594136	126575420	126575464
ENSE00003617110	126554287	126554393
ENSE00003626019	126546324	126546399
ENSE00003627037	126568259	126568356
ENSE00003669740	126593351	126593404
ENSE00003676898	126583932	126584012
ENSE00003681930	126549929	126550002
ENSE00003685110	126582851	126582974

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 97.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.7219 / max 975.0310, expressed in 1574 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63195	34.3662	1573
63196	1.3557	895

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.44	gold quality
ventricular zone	UBERON:0003053	97.42	gold quality
left ovary	UBERON:0002119	97.27	gold quality
right ovary	UBERON:0002118	96.98	gold quality
right adrenal gland cortex	UBERON:0035827	96.76	gold quality
right adrenal gland	UBERON:0001233	96.46	gold quality
ganglionic eminence	UBERON:0004023	96.46	gold quality
amygdala	UBERON:0001876	95.97	gold quality
left adrenal gland	UBERON:0001234	95.90	gold quality
left adrenal gland cortex	UBERON:0035825	95.88	gold quality
stromal cell of endometrium	CL:0002255	95.38	gold quality
putamen	UBERON:0001874	95.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.17	gold quality
nucleus accumbens	UBERON:0001882	95.05	gold quality
caudate nucleus	UBERON:0001873	95.00	gold quality
adrenal cortex	UBERON:0001235	94.65	gold quality
esophagus mucosa	UBERON:0002469	94.65	gold quality
minor salivary gland	UBERON:0001830	94.47	gold quality
mucosa of transverse colon	UBERON:0004991	94.39	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.29	gold quality
adrenal gland	UBERON:0002369	94.13	gold quality
rectum	UBERON:0001052	93.87	gold quality
metanephros cortex	UBERON:0010533	93.80	gold quality
right frontal lobe	UBERON:0002810	93.60	gold quality
skin of abdomen	UBERON:0001416	93.32	gold quality
right lobe of thyroid gland	UBERON:0001119	93.25	gold quality
ectocervix	UBERON:0012249	93.13	gold quality
cingulate cortex	UBERON:0003027	93.10	gold quality
anterior cingulate cortex	UBERON:0009835	93.08	gold quality
spinal cord	UBERON:0002240	93.04	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	129.43
E-GEOD-93593	yes	13.81
E-ANND-3	yes	13.12
E-CURD-53	no	142.90
E-MTAB-6386	no	83.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CRX, NRL, PAX3, SP1, SP3, SP4

miRNA regulators (miRDB)

81 targeting ALDH7A1, 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-4533	100.00	69.48	2758
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-5700	99.64	69.88	2280

Literature-anchored findings (GeneRIF, showing 40)

• Children with pyridoxine-dependent seizures (PDS) have mutations in the ALDH7A1 gene, which encodes antiquitin; these mutations abolish the activity of antiquitin as a delta1-piperideine-6-carboxylate (P6C)-alpha-aminoadipic semialdehyde dehydrogenase. (PMID:16491085)
• allelic and non-allelic heterogeneities of pyridoxine dependent seizures, and cerebrospinal fluid glutamate elevation does not directly correlate with the presence of ALDH7A1 mutations. (PMID:17433748)
• report of 2 unrelated patients affected with pyridoxine-dependent seizures as a result of alpha-aminoadipic semialdehyde dehydrogenase deficiency caused by pathogenic ALDH7A1 mutations; 2 of the 3 mutations are novel & result in erroneous splicing (PMID:18717709)
• The diagnosis of pyridoxine-dependent seizures was confirmed with biochemical and molecular testing revealing elevated alpha-AASA excretion and the presence of 2 different mutations in the antiquitin ( ALDH7A1) gene. (PMID:18854520)
• From this study suggested that defects of ALDH7A1 are almost always the cause of neonatal-onset pyridoxine-dependent seizure and that defects in this gene are also responsible for some but not all later-onset cases. (PMID:19128417)
• In this study both patients in epilepsy reported here had increased CSF alpha-AASA, CSF pipecolic acid, and known or likely pathogenic mutations in the ALDH7A1 gene, consistent with alpha-AASA dehydrogenase deficiency. (PMID:19142996)
• Molecular analysis of the antiquitin gene revealed a novel missense mutation c.57insA, while the mutation of the other allele remained unidentified so far. (PMID:19294602)
• antiquitin was present not only in the cytosol but also in the mitochondria. (PMID:19885858)
• A SNP, rs13182402, within the ALDH7A1 gene was strongly associated with osteoporosis. (PMID:20072603)
• ALDH7A1 is a novel aldehyde dehydrogenase expressed in multiple subcellular compartments that protects against hyperosmotic stress by generating osmolytes and metabolizing toxic aldehydes (PMID:20207735)
• KCNQ and AP3S1, but not MAN2A1 or ALDH7A1 have a role in risk of type 2 diabetes in the Chinese Northern Han population (PMID:20512086)
• The antiquitin 1 oxidation could result in decreased pyridoxal 5-phosphate availability necessary as a cofactor in transaminations, synthesis of glutathione, and synthesis of GABA and dopamine, two neurotransmitters that play a key role in HD pathology. (PMID:20639122)
• Report the genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy due to mutations in ALDH7A1. (PMID:20814824)
• the structural basis for the substrate specificity (PMID:21185811)
• ALDH7A1 mechanistically appears to provide cells protection through multiple pathways (PMID:21338592)
• The aldehyde dehydrogenase enzyme 7A1 is functionally involved in prostate cancer bone metastasis. (PMID:21647815)
• Ongoing diagnostic screening and monitoring revealed that in some individuals with milder ALDH7A1 variants. (PMID:22249334)
• Atypical pyridoxine-dependent epilepsy is due to a pseudoexon in ALDH7A1. (PMID:22305855)
• The effects of a series of twelve disease-associated ALDH7A1 missense mutations on antiquitin activity, were characterized. (PMID:22784480)
• A novel missense mutation c.1364T>C (p.Leu455Pro)was detected in in two unrelated Tunisian families with pyridoxine-dependent epilepsy. (PMID:23054014)
• molecular analysis of seven Pyridoxine-dependent epilepsy Tunisian patients revealed a common missense c.1364T>C mutation in the ALDH7A1 gene; the conservation of a single genotype within the c.1364T > C mutation suggested that this variation has a single origin (PMID:23376216)
• For patients with NSCLC, low ALDH7A1 expression was associated with a decreased incidence of cancer recurrence. (PMID:23647301)
• Pyridoxine dependent epilepsy (PDE) is caused by mutations in the ALDH7A1 gene (PDE-ALDH7A1) encoding alpha-aminoadipic semialdehyde dehydrogenase (alpha-AASAD) enzyme in the lysine catabolic pathway (PMID:23683770)
• Antiquitin is expressed within glial cells in the brain and its dysfunction in pyridoxine-dependent epilepsy is associated with neuronal migration abnormalities. (PMID:24122892)
• Clinical diagnosis, treatment, and ALDH7A1 mutations in pyridoxine-dependent epilepsy in three Chinese infants (PMID:24664145)
• our study indicated that the ALDH7A1 rs13182402 polymorphism was associated with risk of ESCC in Chinese populations. (PMID:25213698)
• Using a custom array, study identified heterozygous intragenic deletions in the ALDH7A1 gene in 5 of 6 patients with pyridoxine-dependent epilepsy and positive biomarkers who had only a single mutation identified by conventional sequence analysis (PMID:26224730)
• Direct sequencing of the ALDH7A1 gene revealed one novel (c.297delG, p.Trp99*) and two already reported (c.328C>T, p.Arg110*; c.584A>G, p.Asn195Ser) mutations (PMID:26232297)
• Binding to ALDH7A1 is associated with movement of the C-terminus into the active site which stabilizes the substrate anchor loop. (PMID:26260980)
• This study found five novel mutations of ALDH7A1 gene in pyridoxin dependent epilepsy. (PMID:26555630)
• We present the clinical and molecular genetic findings of two patients with c.1597_1597delG mutations in ALDH7A1 gene. (PMID:27186704)
• Wild-type ALDH7A1 is shown to exist in a dimer-tetramer equilibrium with a dissociation constant of 16 muM. In contrast to the wild-type enzyme, the variants reside in monomer-dimer equilibria and are apparently incapable of forming a tetrameric species, even at high enzyme concentration. (PMID:28087462)
• Mutations in the ALDH7A1 gene encoding alpha-amino-adipic semialdehyde (alpha-AASA) dehydrogenase (antiquitin) have been identified as the cause of PDE. We report on a novel ALDH7A1 mutation in a Tunisian child with PDE. (PMID:28131559)
• results suggest that the C-terminus of ALDH7A1 is crucial for the maintenance of both the oligomeric state and the catalytic activity. (PMID:29045138)
• By using mass spectrometry techniques, we further explored the metabolic effect of aldh7a1 knockout. Impaired lysine degradation with accumulation of PDE biomarkers, B6 deficiency, and low gamma-aminobutyric acid levels were observed in the aldh7a1(-/-) larvae, which may play a significant role in the seizure phenotype and PDE pathogenesis. (PMID:29061647)
• We describe the case of two siblings, children of consanguineous parents, who carried a novel homozygous missense mutation of the ALDH7A1gene (PMID:30005813)
• This report provides a comprehensive overview of known ALDH7A1 mutations that cause pyridoxine dependent epilepsy (PDE), and suggests that PDE may be more common than initially estimated. [review] (PMID:30043187)
• Results suggest the NAD+ cofactor of aldehyde dehydrogenase 7 family member A1 protein (ALDH7A1) dramatically enhances tetramerization of the enzyme. (PMID:30184263)
• Low ALDH7A1 protein levels correlated with poor clinical outcome. (PMID:30486822)
• The study provides first evidence that the saccharopine pathway is the major route of lysine degradation in cultured human brain cells. These results support inhibition of the saccharopine pathway as a new treatment option for antiquitin deficiency. (PMID:30767241)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	aldh7a1	ENSDARG00000018426
mus_musculus	Aldh7a1	ENSMUSG00000053644
rattus_norvegicus	Aldh7a1	ENSRNOG00000014645
drosophila_melanogaster	Aldh7A1	FBGN0036857
caenorhabditis_elegans		WBGENE00000115

Paralogs (17): ALDH3B1 (ENSG00000006534), ALDH3A2 (ENSG00000072210), ALDH3A1 (ENSG00000108602), ALDH2 (ENSG00000111275), ALDH5A1 (ENSG00000112294), ALDH8A1 (ENSG00000118514), ALDH6A1 (ENSG00000119711), ALDH1A2 (ENSG00000128918), ALDH3B2 (ENSG00000132746), ALDH1L2 (ENSG00000136010), ALDH1B1 (ENSG00000137124), ALDH9A1 (ENSG00000143149), ALDH1L1 (ENSG00000144908), ALDH4A1 (ENSG00000159423), ALDH16A1 (ENSG00000161618), ALDH1A1 (ENSG00000165092), ALDH1A3 (ENSG00000184254)

Protein

Protein identifiers

Alpha-aminoadipic semialdehyde dehydrogenase — P49419 (reviewed: P49419)

Alternative names: Aldehyde dehydrogenase family 7 member A1, Antiquitin-1, Betaine aldehyde dehydrogenase, Delta1-piperideine-6-carboxylate dehydrogenase

All UniProt accessions (18): A0A0J9YWF7, A0A0J9YWK1, A0A0J9YWM6, A0A1B0GTG2, A0A1B0GTJ4, A0A1B0GTY9, A0A1B0GUA1, A0A1B0GUY0, A0A1B0GV49, P49419, A0A1B0GVU0, A0A1B0GW65, A0A1B0GW77, A0A1B0GW82, F8VVF2, F8WD33, F8WDY6, H0YHM6

UniProt curated annotations — full annotation on UniProt →

Function. Aldehyde dehydrogenase enzyme that mediates important protective effects. Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes. Involved in cellular defense against hyperosmotic stress by metabolizing betaine aldehyde to betaine, an important cellular osmolyte and methyl donor. Involved in lysine catabolism in the brain by mediating the conversion of L-aminoadipate-semialdehyde ((S)-2-amino-6-oxohexanoate) to L-2-aminoadipate. Acts as a key inhibitor of ferroptosis both by generating membrane NADH and decreasing the level of reactive aldehydes. Recruited to plasma membrane in response to ferroptotic stress and phosphorylation by AMPK, generating membrane NADH to support AIFM2/FSP1 activity, an essential ferroptosis suppressor protein. Also directly inhibits ferroptosis by decreasing lipid peroxidation via consumption of reactive aldehydes, such as 4-hydroxynonenal (4-HNE) and malonaldehyde. Also acts as a regulator of cellular energy homeostasis in response to cellular energy stress, such as starvation and hypoxia, by inhibiting COPI-mediated intracellular transport, thereby reducing cellular energy consumption.

Subunit / interactions. Homotetramer.

Subcellular location. Mitochondrion Cytoplasm. Cytosol. Cell membrane. Golgi apparatus membrane. Nucleus.

Tissue specificity. Abundant in hepatoma cells and fetal cochlea, ovary, eye, heart, adrenal gland, liver and kidney. Low levels present in adult peripheral blood leukocytes and fetal brain, thymus, spleen, skeletal muscle, lung and tongue.

Post-translational modifications. Phosphorylation at Ser-102 by AMPK in response to cellular stress, such as hypoxia or ferroptotic stress, promotes membrane localization and generation of membrane NADH.

Disease relevance. Epilepsy, early-onset, 4, vitamin B6-dependent (EPEO4) [MIM:266100] An autosomal recessive neurologic disorder ocharacterized by a combination of various seizure types. It usually occurs in the first hours of life and is unresponsive to standard anticonvulsants, responding only to immediate administration of pyridoxine hydrochloride. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by 4-diethylaminobenzaldehyde (DEAB); inhibition is irreversible via formation of a stable covalent acyl-enzyme stalled intermediate.

Pathway. Amine and polyamine biosynthesis; betaine biosynthesis via choline pathway; betaine from betaine aldehyde: step 1/1.

Similarity. Belongs to the aldehyde dehydrogenase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P49419-1	1, hALDH7A1_v1	yes
P49419-2	2, hALDH7A1_v2
P49419-4	4

RefSeq proteins (3): NP_001173, NP_001188306, NP_001189333 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015590	Aldehyde_DH_dom	Domain
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
IPR044638	ALDH7A1-like	Family

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)
• EC 1.2.1.31 — L-aminoadipate-semialdehyde dehydrogenase (BRENDA: 17 organisms, 29 substrates, 35 inhibitors, 21 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

140 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), 9 shown:

• (S)-2-amino-6-oxohexanoate + NAD(+) + H2O = L-2-aminoadipate + NADH + 2 H(+) (RHEA:12308)
• betaine aldehyde + NAD(+) + H2O = glycine betaine + NADH + 2 H(+) (RHEA:15305)
• an aldehyde + NAD(+) + H2O = a carboxylate + NADH + 2 H(+) (RHEA:16185)
• octanal + NAD(+) + H2O = octanoate + NADH + 2 H(+) (RHEA:44100)
• (E)-4-hydroxynon-2-enal + NAD(+) + H2O = (E)-4-hydroxynon-2-enoate + NADH + 2 H(+) (RHEA:67248)
• malonaldehyde + NAD(+) + H2O = 3-oxopropanoate + NADH + 2 H(+) (RHEA:67252)
• hexanal + NAD(+) + H2O = hexanoate + NADH + 2 H(+) (RHEA:67276)
• nonanal + NAD(+) + H2O = nonanoate + NADH + 2 H(+) (RHEA:69759)
• (E)-non-2-enal + NAD(+) + H2O = (E)-non-2-enoate + NADH + 2 H(+) (RHEA:69767)

UniProt features (120 total): sequence variant 32, strand 24, helix 22, binding site 18, modified residue 7, turn 4, mutagenesis site 4, active site 2, splice variant 2, transit peptide 1, chain 1, initiator methionine 1, site 1, sequence conflict 1

Structure

Experimental structures (PDB)

20 structures.

PDB	Method	Resolution (Å)
2J6L	X-RAY DIFFRACTION	1.3
6O4C	X-RAY DIFFRACTION	1.7
6O4E	X-RAY DIFFRACTION	1.75
6O4I	X-RAY DIFFRACTION	1.75
4ZUL	X-RAY DIFFRACTION	1.76
6O4B	X-RAY DIFFRACTION	1.85
6O4L	X-RAY DIFFRACTION	1.85
6O4D	X-RAY DIFFRACTION	1.88
4ZVX	X-RAY DIFFRACTION	1.9
4ZVY	X-RAY DIFFRACTION	1.9
6O4F	X-RAY DIFFRACTION	1.9
4X0U	X-RAY DIFFRACTION	1.95
4ZUK	X-RAY DIFFRACTION	2
6V0Z	X-RAY DIFFRACTION	2.02
6O4G	X-RAY DIFFRACTION	2.05
6O4H	X-RAY DIFFRACTION	2.05
6O4K	X-RAY DIFFRACTION	2.06
6U2X	X-RAY DIFFRACTION	2.15
4X0T	X-RAY DIFFRACTION	2.4
4ZVW	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49419-F1	95.09	0.94

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): 296 (proton acceptor); 195 (transition state stabilizer); 330 (nucleophile)

Ligand- & substrate-binding residues (18): 259; 259; 275; 275; 296; 297; 297; 331; 427; 427; 489; 490 …

Post-translational modifications (7): 2, 94, 94, 130, 462, 500, 537

Mutagenesis-validated functional residues (4):

Position	Phenotype
130	abolished phosphorylation by ampk and recruitment to membranes.
130	mimics phosphorylation; promoting plasma membrane recruitment and ability to generate membrane nadh.
174	does not affect phosphorylation by ampk and recruitment to membranes.
296	abolished aldehyde dehydrogenase activity, leading to decreased levels of membrane nadh.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6798163	Choline catabolism
R-HSA-71064	Lysine catabolism
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 406 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, MODULE_93, MODULE_52, GOBP_LYSOSOMAL_TRANSPORT, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, CHANDRAN_METASTASIS_DN, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION

GO Biological Process (13): aldehyde metabolic process (GO:0006081), obsolete lysine catabolic process (GO:0006554), Golgi to endosome transport (GO:0006895), sensory perception of sound (GO:0007605), endosome to lysosome transport (GO:0008333), obsolete glycine betaine biosynthetic process from choline (GO:0019285), L-lysine catabolic process (GO:0019477), choline catabolic process (GO:0042426), negative regulation of Golgi to plasma membrane protein transport (GO:0042997), plasma membrane to endosome transport (GO:0048227), energy homeostasis (GO:0097009), negative regulation of ferroptosis (GO:0110076), negative regulation of endosome to plasma membrane protein transport (GO:1905750)

GO Molecular Function (8): aldehyde dehydrogenase (NAD+) activity (GO:0004029), L-aminoadipate-semialdehyde dehydrogenase [NAD(P)+] activity (GO:0004043), betaine-aldehyde dehydrogenase (NAD+) activity (GO:0008802), oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor (GO:0016655), identical protein binding (GO:0042802), 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 (8): Golgi membrane (GO:0000139), nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	2
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intercellular transport	2
vesicle-mediated transport	2
negative regulation of protein localization to plasma membrane	2
aldehyde dehydrogenase [NAD(P)+] activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
cellular anatomical structure	2
metabolic process	1
post-Golgi vesicle-mediated transport	1
cytosolic transport	1
sensory perception of mechanical stimulus	1
lysosomal transport	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
choline metabolic process	1
biogenic amine catabolic process	1
regulation of Golgi to plasma membrane protein transport	1
Golgi to plasma membrane protein transport	1
negative regulation of protein transport	1
multicellular organismal-level homeostasis	1
negative regulation of programmed cell death	1
ferroptosis	1
regulation of ferroptosis	1
negative regulation of intracellular protein transport	1
endosome to plasma membrane protein transport	1
regulation of endosome to plasma membrane protein transport	1
negative regulation of endocytic recycling	1
aldehyde dehydrogenase (NAD+) activity	1
oxidoreductase activity, acting on NAD(P)H	1
protein binding	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on the aldehyde or oxo group of donors	1
Golgi apparatus	1
bounding membrane of organelle	1
mitochondrion	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
extracellular vesicle	1

Protein interactions and networks

STRING

4351 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALDH7A1	PDE4A	P27815	972
ALDH7A1	PDE7A	Q13946	949
ALDH7A1	PDE5A	O76074	946
ALDH7A1	RAPGEF3	O95398	946
ALDH7A1	PDE4B	Q07343	942
ALDH7A1	CALML6	Q8TD86	914
ALDH7A1	CALML4	Q96GE6	914
ALDH7A1	CALML3	P27482	913
ALDH7A1	CALML5	Q9NZT1	913
ALDH7A1	PDE4D	Q08499	910
ALDH7A1	PDE4C	Q08493	909
ALDH7A1	RAPGEF4	Q8WZA2	908
ALDH7A1	PDE3A	Q14432	899
ALDH7A1	AKAP1	Q92667	895
ALDH7A1	CALM1	P02593	893
ALDH7A1	PDE10A	Q9Y233	893

IntAct

44 interactions, top by confidence:

A	B	Type	Score
PKNOX2	PBX1	psi-mi:“MI:0914”(association)	0.550
XRCC4	NFKB1	psi-mi:“MI:0914”(association)	0.530
ALDH7A1	EPS8	psi-mi:“MI:0915”(physical association)	0.510
EPS8	ALDH7A1	psi-mi:“MI:0915”(physical association)	0.510
rep	NKRF	psi-mi:“MI:0914”(association)	0.500
DOCK8	ALDH7A1	psi-mi:“MI:0915”(physical association)	0.400
ATP1A1	ALDH7A1	psi-mi:“MI:0915”(physical association)	0.400
JUN		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
NBEAL2	HAX1	psi-mi:“MI:0914”(association)	0.350
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
rep	PSMD9	psi-mi:“MI:0914”(association)	0.350
RIPK4	TBCA	psi-mi:“MI:0914”(association)	0.350
MAPK15	TIMM8A	psi-mi:“MI:0914”(association)	0.350
UBA5	PGK1	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
GIGYF1	DYNC1I1	psi-mi:“MI:0914”(association)	0.350
CD2BP2	PRPF4	psi-mi:“MI:0914”(association)	0.350
COPA	ESYT2	psi-mi:“MI:0914”(association)	0.350
COPB2	ESYT2	psi-mi:“MI:0914”(association)	0.350
COPE	ESYT2	psi-mi:“MI:0914”(association)	0.350
TFPT	KRBA1	psi-mi:“MI:0914”(association)	0.350
LDHAL6A	LDHA	psi-mi:“MI:0914”(association)	0.350
SIKE1	ALDH7A1	psi-mi:“MI:0914”(association)	0.350

BioGRID (149): ALDH7A1 (Affinity Capture-MS), ALDH7A1 (Affinity Capture-MS), ABAT (Co-fractionation), CAT (Co-fractionation), CPT2 (Co-fractionation), FAHD2A (Co-fractionation), GOT1 (Co-fractionation), HIBCH (Co-fractionation), PRDX5 (Co-fractionation), SORD (Co-fractionation), ALDH7A1 (Affinity Capture-MS), ALDH7A1 (Affinity Capture-MS), ALDH7A1 (Affinity Capture-MS), ALDH7A1 (Affinity Capture-MS), ALDH7A1 (Affinity Capture-MS)

ESM2 similar proteins: A7YWE4, O74766, O75891, P07275, P0C2X9, P25795, P28037, P30038, P46562, P49419, P51649, P51650, P54889, P78568, P83401, Q02252, Q02253, Q07536, Q0WM29, Q141D3, Q1GV29, Q29HB2, Q2KJC9, Q2SKP1, Q3MSM3, Q3MSM4, Q3SY69, Q41247, Q54RA2, Q5RFM9, Q64057, Q6A2H0, Q6A2H1, Q6A2H2, Q6JQN1, Q7KW39, Q7QC84, Q7SY23, Q802W2, Q8BWF0

Diamond homologs: A0R909, A0RDW1, A4IPB2, A4IPF5, A4VKC2, A5YBJ3, A6UVT6, A7GKJ4, A9VF06, A9VMS6, A9VRG6, B0KN18, B0RNV0, B0VST2, B2HV80, B3VMC0, B7GFV3, B7H4V1, B7H597, B7HSW8, B7IUW8, B7IW48, B7JM99, B7VQ28, B8DCT8, B9F3B6, B9J1L9, C1EV77, C1KZ99, C3L546, C3PBP4, C7A2A0, D4GP41, O06478, O14293, P08157, P11884, P17202, P20000, P24549

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1205 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	110
Likely pathogenic	67
Uncertain significance	353
Likely benign	433
Benign	93

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012739	NM_001182.5(ALDH7A1):c.645C>A (p.Cys215Ter)	Pathogenic
1033773	NM_001182.5(ALDH7A1):c.1412_1415+9delinsGTTGGG	Pathogenic
1067854	NM_001182.5(ALDH7A1):c.1192G>A (p.Gly398Arg)	Pathogenic
1071019	NC_000005.9:g.(?125880657)(125930890_?)del	Pathogenic
1072992	NM_001182.5(ALDH7A1):c.241C>T (p.Arg81Ter)	Pathogenic
1074016	NM_001182.5(ALDH7A1):c.834G>C (p.Val278=)	Pathogenic
1074455	NM_001182.5(ALDH7A1):c.1061A>G (p.Tyr354Cys)	Pathogenic
1075197	NM_001182.5(ALDH7A1):c.538dup (p.Glu180fs)	Pathogenic
1076094	NM_001182.5(ALDH7A1):c.130G>T (p.Glu44Ter)	Pathogenic
1300418	NM_001182.5(ALDH7A1):c.376C>T (p.Gln126Ter)	Pathogenic
1328029	NM_001182.5(ALDH7A1):c.1483G>A (p.Ala495Thr)	Pathogenic
1341558	NM_001182.5(ALDH7A1):c.187G>T (p.Gly63Ter)	Pathogenic
1341559	NM_001182.5(ALDH7A1):c.1411_1412insG (p.Leu471fs)	Pathogenic
1342147	NC_000005.10:g.126508361_126769360del	Pathogenic
1355701	NM_001182.5(ALDH7A1):c.1088G>A (p.Trp363Ter)	Pathogenic
1409272	NC_000005.9:g.(?125929344)(125930707_?)del	Pathogenic
1451488	NM_001182.5(ALDH7A1):c.841C>T (p.Gln281Ter)	Pathogenic
1456756	NM_001182.5(ALDH7A1):c.1477G>T (p.Gly493Ter)	Pathogenic
1457545	NM_001182.5(ALDH7A1):c.1072C>T (p.Arg358Ter)	Pathogenic
1685518	NM_001182.5(ALDH7A1):c.509C>T (p.Pro170Leu)	Pathogenic
1696912	NM_001182.5(ALDH7A1):c.984del (p.Arg329fs)	Pathogenic
1704270	NM_001182.5(ALDH7A1):c.1327G>T (p.Glu443Ter)	Pathogenic
1705018	NM_001182.5(ALDH7A1):c.388_518-1428del	Pathogenic
1705019	Single allele	Pathogenic
1709791	NM_001182.5(ALDH7A1):c.500del (p.Pro167fs)	Pathogenic
17995	NM_001182.5(ALDH7A1):c.328C>T (p.Arg110Ter)	Pathogenic
17996	NM_001182.5(ALDH7A1):c.518-1G>C	Pathogenic
17997	NM_001182.5(ALDH7A1):c.312+2T>A	Pathogenic
17998	NM_001182.5(ALDH7A1):c.596C>T (p.Ala199Val)	Pathogenic
18000	NM_001182.5(ALDH7A1):c.1224T>G (p.Tyr408Ter)	Pathogenic

SpliceAI

2813 predictions. Top by Δscore:

Variant	Effect	Δscore
5:126550198:AAG:A	donor_gain	1.0000
5:126550292:TT:T	acceptor_gain	1.0000
5:126550294:C:CC	acceptor_gain	1.0000
5:126552015:TTTTA:T	donor_loss	1.0000
5:126552016:TTTAC:T	donor_loss	1.0000
5:126552017:TTA:T	donor_loss	1.0000
5:126552018:TACC:T	donor_loss	1.0000
5:126552019:A:C	donor_loss	1.0000
5:126552136:ACCTA:A	acceptor_loss	1.0000
5:126552137:CCTAA:C	acceptor_gain	1.0000
5:126552138:C:CA	acceptor_loss	1.0000
5:126552138:C:CC	acceptor_gain	1.0000
5:126552139:T:A	acceptor_loss	1.0000
5:126552141:A:C	acceptor_gain	1.0000
5:126554283:TTACC:T	donor_loss	1.0000
5:126554284:TA:T	donor_loss	1.0000
5:126554285:A:AT	donor_loss	1.0000
5:126554286:CCT:C	donor_loss	1.0000
5:126554305:TGTGC:T	donor_gain	1.0000
5:126554390:TTAG:T	acceptor_gain	1.0000
5:126554391:TAG:T	acceptor_gain	1.0000
5:126554394:C:CC	acceptor_gain	1.0000
5:126556016:C:CC	acceptor_gain	1.0000
5:126559336:T:C	acceptor_gain	1.0000
5:126559336:T:TC	acceptor_gain	1.0000
5:126559361:A:T	acceptor_gain	1.0000
5:126559368:C:CT	acceptor_gain	1.0000
5:126559369:A:T	acceptor_gain	1.0000
5:126561078:CTTA:C	donor_loss	1.0000
5:126561079:TTA:T	donor_loss	1.0000

AlphaMissense

3508 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:126549930:A:C	F496L	1.000
5:126549930:A:T	F496L	1.000
5:126549932:A:G	F496L	1.000
5:126577141:G:C	F196L	1.000
5:126577141:G:T	F196L	1.000
5:126577143:A:G	F196L	1.000
5:126577144:A:C	N195K	1.000
5:126577144:A:T	N195K	1.000
5:126582959:C:A	G137W	1.000
5:126546352:A:G	W513R	0.999
5:126546352:A:T	W513R	0.999
5:126549952:C:T	G489E	0.999
5:126549954:A:C	S488R	0.999
5:126549954:A:T	S488R	0.999
5:126549956:T:G	S488R	0.999
5:126549966:G:C	N484K	0.999
5:126549966:G:T	N484K	0.999
5:126549982:C:T	G479D	0.999
5:126549984:A:C	C478W	0.999
5:126550203:A:G	W470R	0.999
5:126550203:A:T	W470R	0.999
5:126550237:G:C	S458R	0.999
5:126550237:G:T	S458R	0.999
5:126550239:T:G	S458R	0.999
5:126550240:A:C	S457R	0.999
5:126550240:A:T	S457R	0.999
5:126550242:T:G	S457R	0.999
5:126550247:A:G	L455P	0.999
5:126552051:A:C	F429L	0.999
5:126552051:A:T	F429L	0.999

dbSNP variants (sampled 300 via entrez): RS1000156955 (5:126559958 T>C), RS1000186728 (5:126586054 T>C), RS1000198525 (5:126551256 G>A,T), RS1000303609 (5:126564647 C>G), RS1000315607 (5:126577318 T>G), RS1000357564 (5:126552366 A>G), RS1000395526 (5:126569137 G>C), RS1000454021 (5:126591742 G>A), RS1000474588 (5:126571071 T>C,G), RS1000475338 (5:126557447 C>T), RS1000529443 (5:126552672 C>A,G,T), RS1000588638 (5:126544881 C>G), RS1000645458 (5:126552313 G>A,T), RS1000760530 (5:126558572 A>G), RS1000791284 (5:126576108 A>G)

Disease associations

OMIM: gene MIM:107323 | disease phenotypes: MIM:169500, MIM:308350, MIM:266100, MIM:614558

GenCC curated gene-disease

Disease	Classification	Inheritance
pyridoxine-dependent epilepsy caused by ALDH7A1 mutant	Definitive	Autosomal dominant
pyridoxine-dependent epilepsy	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
pyridoxine-dependent epilepsy	Definitive	AR

Mondo (8): pyridoxine-dependent epilepsy (MONDO:0009945), adult-onset autosomal dominant demyelinating leukodystrophy (MONDO:0008215), developmental and epileptic encephalopathy, 1 (MONDO:0010632), pyridoxine-dependent epilepsy caused by ALDH7A1 mutant (MONDO:0020741), congenital nervous system disorder (MONDO:0002320), epilepsy (MONDO:0005027), intellectual disability (MONDO:0001071), developmental and epileptic encephalopathy, 13 (MONDO:0013801)

Orphanet (4): Pyridoxine-dependent-developmental and epileptic encephalopathy (Orphanet:3006), Adult-onset autosomal dominant leukodystrophy (Orphanet:99027), Non-specific early-onset epileptic encephalopathy (Orphanet:442835), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000238	Hydrocephalus
HP:0000273	Facial grimacing
HP:0000486	Strabismus
HP:0000496	Abnormality of eye movement
HP:0000711	Restlessness
HP:0000737	Irritability
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001557	Prenatal movement abnormality
HP:0001943	Hypoglycemia
HP:0002069	Bilateral tonic-clonic seizure
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002123	Generalized myoclonic seizure
HP:0002133	Status epilepticus
HP:0002188	Delayed CNS myelination
HP:0002280	Enlarged cisterna magna
HP:0002521	Hypsarrhythmia
HP:0002643	Neonatal respiratory distress
HP:0003128	Lactic acidosis
HP:0003623	Neonatal onset
HP:0007359	Focal-onset seizure
HP:0010819	Atonic seizure
HP:0010841	Multifocal epileptiform discharges
HP:0010845	EEG with generalized slow activity
HP:0010851	EEG with burst suppression

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000560_1	Osteoporosis	2.000000e-09
GCST005175_42	Coronary artery calcified atherosclerotic plaque (90 or 130 HU threshold) in type 2 diabetes	5.000000e-07
GCST007552_35	Colorectal cancer	4.000000e-08
GCST009391_731	Metabolite levels	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0009774	serine measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C566813	Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant (supp.)
C536254	Pyridoxine-dependent epilepsy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066883 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.32	Kd	4.821	nM	CHEMBL5653589
8.32	ED50	4.821	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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	2147842: Binding affinity to human ALDH7A1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0048	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects expression	3
sodium arsenite	affects cotreatment, increases abundance, affects acetylation, affects methylation, decreases expression	3
Valproic Acid	decreases expression, decreases methylation	3
Cyclosporine	decreases expression	3
perfluorooctanoic acid	decreases expression, increases expression	2
Air Pollutants	increases expression, increases oxidation, decreases expression, affects cotreatment, increases abundance	2
Doxorubicin	affects response to substance, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance, affects expression	2
allysine	affects binding, increases oxidation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
biochanin A	decreases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases oxidation, increases abundance	1
pirinixic acid	affects binding, decreases expression, increases activity	1
deoxynivalenol	decreases expression	1
n-hexanal	decreases response to substance	1
arsenite	affects binding, increases reaction	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
ochratoxin A	decreases acetylation	1
4-hydroxy-2-nonenal	decreases response to substance, increases metabolic processing	1
artenimol	affects binding	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment, increases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
pentanal	decreases expression	1
chloropicrin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650884	Binding	Binding affinity to human ALDH7A1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

5 cell lines: 5 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C6SF	SCTCi019-B	Induced pluripotent stem cell	Male
CVCL_D6S7	SCTCi026-A	Induced pluripotent stem cell	Female
CVCL_E2U2	SCTCi027-A	Induced pluripotent stem cell	Male
CVCL_E2U3	SCTCi028-A	Induced pluripotent stem cell	Female
CVCL_E2U4	SCTCi029-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy