pyridoxine-dependent epilepsy caused by ALDH7A1 mutant

Summary

pyridoxine-dependent epilepsy caused by ALDH7A1 mutant (MONDO:0020741) is a disease caused by ALDH7A1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: ALDH7A1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pyridoxine-dependent epilepsy caused by ALDH7A1 mutant
Mondo ID	MONDO:0020741
OMIM	266100
DOID	DOID:0070519
GARD	0025233
Is cancer (heuristic)	no

Also known as: EPD · epilepsy, pyridoxine-dependent · pyridoxine-dependent epilepsy caused by ALDH7A1 mutant

Data availability: 2 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of biogenic amine metabolism and transport › inborn disorder of pyridoxine metabolism › pyridoxine-dependent epilepsy › pyridoxine-dependent epilepsy caused by ALDH7A1 mutant

Related subtypes (1): epilepsy, early-onset, vitamin B6-dependent

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
17994	NM_001182.5(ALDH7A1):c.1279G>C (p.Glu427Gln)	ALDH7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374140	NM_001182.5(ALDH7A1):c.1566-1G>T	ALDH7A1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ALDH7A1	Definitive	Autosomal dominant	pyridoxine-dependent epilepsy caused by ALDH7A1 mutant	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ALDH7A1	Orphanet:3006	Pyridoxine-dependent-developmental and epileptic encephalopathy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ALDH7A1	HGNC:877	ENSG00000164904	P49419	Alpha-aminoadipic semialdehyde dehydrogenase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ALDH7A1	Alpha-aminoadipic semialdehyde dehydrogenase	Aldehyde dehydrogenase enzyme that mediates important protective effects.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ALDH7A1	Enzyme (other)	yes	1.2.1.3	Aldehyde_DH_dom, Ald_DH/histidinol_DH, Ald_DH_N

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left ovary	1
right lobe of liver	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ALDH7A1	255	ubiquitous	marker	right lobe of liver, ventricular zone, left ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALDH7A1	4,544

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ALDH7A1	P49419	20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Choline catabolism	1	1427.5×	0.002	ALDH7A1
Lysine catabolism	1	1142.0×	0.002	ALDH7A1
Metabolism of amino acids and derivatives	1	67.6×	0.020	ALDH7A1
Metabolism	1	11.6×	0.086	ALDH7A1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
L-lysine catabolic process	1	16852.0×	4e-04	ALDH7A1
negative regulation of endosome to plasma membrane protein transport	1	16852.0×	4e-04	ALDH7A1
obsolete glycine betaine biosynthetic process from choline	1	8426.0×	5e-04	ALDH7A1
choline catabolic process	1	4213.0×	8e-04	ALDH7A1
negative regulation of Golgi to plasma membrane protein transport	1	2808.7×	9e-04	ALDH7A1
obsolete lysine catabolic process	1	2407.4×	9e-04	ALDH7A1
plasma membrane to endosome transport	1	1532.0×	0.001	ALDH7A1
aldehyde metabolic process	1	1296.3×	0.001	ALDH7A1
Golgi to endosome transport	1	1053.2×	0.001	ALDH7A1
negative regulation of ferroptosis	1	802.5×	0.002	ALDH7A1
endosome to lysosome transport	1	337.0×	0.004	ALDH7A1
energy homeostasis	1	271.8×	0.004	ALDH7A1
sensory perception of sound	1	100.9×	0.010	ALDH7A1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ALDH7A1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ALDH7A1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALDH7A1	1.2.1.3, 1.2.1.31	aldehyde dehydrogenase (NAD+), L-aminoadipate-semialdehyde dehydrogenase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	ALDH7A1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ALDH7A1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.