ALDH1A2

Chr 15

aldehyde dehydrogenase 1 family member A2

Also known as: DIH4, RALDH(II), RALDH2, RALDH2-T

NCBI Gene: 8854 ENSG00000128918 UniProt: O94788

This protein belongs to the aldehyde dehydrogenase family of proteins. The product of this gene is an enzyme that catalyzes the synthesis of retinoic acid (RA) from retinaldehyde. Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal signaling molecule that functions in developing and adult tissues. The studies of a similar mouse gene suggest that this enzyme and the cytochrome CYP26A1, concurrently establish local embryonic retinoic acid levels which facilitate posterior organ development and prevent spina bifida. Four transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2011]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDiaphragmatic hernia 4, with cardiovascular defects

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.45

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.363

Z-score 3.69

OE 0.23 (0.12–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.44Z-score

OE missense 0.76 (0.68–0.85)

215 obs / 283.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.23 (0.12–0.45)

0≤0.351.4

Missense OE?0.76 (0.68–0.85)

0≤0.61.4

Synonymous OE?1.22

0≤1.21.6

LoF obs/exp: 6 / 26.5Missense obs/exp: 215 / 283.1Syn Z: -1.75

Background carrier burden — how many people carry a rare variant somewhere in ALDH1A2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

654 rare PASS variants

Rare truncating (LoF)

1 in 2,300

103 rare PASS variants

Rare synonymous (reference)

1 in 150

314 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ALDH1A2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 2,700
South Asian	~43k	1 in 92	1 in 1,800
Remaining (unassigned)	~30k	1 in 120	1 in 3,300
European (Finnish)	~27k	1 in 450	1 in 3,000
Admixed American	~22k	1 in 140	1 in 1,200
African / African American	~21k	1 in 160	1 in 3,800
East Asian	~20k	1 in 150	1 in 1,200
Ashkenazi Jewish	~13k	1 in 440	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 120	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 13 of 13 coding exons well covered in gnomAD exomes. Genomes: 12 of 13 (exon 5 below).? see exons ↓