ALDH7A1

Chr 5

aldehyde dehydrogenase 7 family member A1

Also known as: ATQ1, EPD, EPEO4, PDE

NCBI Gene: 501 ENSG00000164904 UniProt: P49419

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 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 ResearchGenerating clinical summary…

LOFmechanismLOEUF 1.24

Clinical Summary— ALDH7A1

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Gene-Disease Validity (ClinGen)

pyridoxine-dependent epilepsy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

196 unique Pathogenic / Likely Pathogenic· 352 VUS of 1179 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ALDH7A1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.24LOEUF

pLI 0.000

Z-score 0.37

OE 0.93 (0.71–1.24)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.37Z-score

OE missense 0.94 (0.85–1.04)

278 obs / 295.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.93 (0.71–1.24)

0≤0.351.4

Missense OE?0.94 (0.85–1.04)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 35 / 37.4Missense obs/exp: 278 / 295.8Syn Z: -0.18

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveALDH7A1-related pyridoxine-dependent epilepsyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6647th %ile

GOF

0.6345th %ile

LOF

0.4431th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

1179 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic98

Likely Pathogenic98

VUS352

Likely Benign442

Benign89

Conflicting74

Pathogenic

Likely Pathogenic

352

VUS

442

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	59	22	15	2	98
Likely Pathogenic	44	44	10	0	98
VUS	6	259	81	6	352
Likely Benign	0	4	256	182	442
Benign	0	0	89	0	89
Conflicting	—				74
Total	109	329	451	190	1,153

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

17 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap ALDH7A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →