ALDH7A1

Chr 5AR

aldehyde dehydrogenase 7 family member A1

Also known as: ATQ1, EPD, EPEO4, PDE

NCBI Gene: 501 ENSG00000164904 UniProt: P49419 OMIM: 107323

ALDH7A1 encodes an aldehyde dehydrogenase enzyme that metabolizes aldehydes from lipid peroxidation and alcohol metabolism, and converts betaine aldehyde to betaine for cellular osmotic protection. Mutations cause pyridoxine-dependent epilepsy with early onset, inherited in an autosomal recessive pattern. The gene is not constrained against loss-of-function variants, and patients typically respond to vitamin B6 supplementation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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. [provided by RefSeq, Jan 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Epilepsy, early-onset, 4, vitamin B6-dependentMIM #266100

Clinical highlights

Management implications

Seizures respond to pyridoxine; add lysine-reduction therapy for neurodevelopment.Lifelong pyridoxine plus lysine-reduction therapy; treat empirically in neonatal refractory seizures.

ALDH7A1: treatable — pyridoxine

Gene-disease validity (ClinGen)

pyridoxine-dependent epilepsy · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.24

LOEUF

LOF

Mechanism· G2P

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GeneReview available — ALDH7A1

Authoritative clinical overview · Recommended first read

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Treatment implicationsTreatable

Pyridoxine-dependent epilepsy (PDE-ALDH7A1)

Lifelong pyridoxine plus lysine-reduction therapy; treat empirically in neonatal refractory seizures.

Seizures respond to pyridoxine; add lysine-reduction therapy for neurodevelopment.

Treatment of choice

pyridoxine (vitamin B6)adjunct lysine restriction ± arginine

Coughlin et al. 2021 consensus, J Inherit Metab Dis. Confirm with a neurologist and current guidelines. Functional class (GOF/LOF) is from published functional/segregation data, never inferred from the variant. As of 2026-07. Curated from the clinical genetics/neurology literature (cited per gene). Decision-support, not prescribing.