ALDH3B2

Chr 11

aldehyde dehydrogenase 3 family member B2

Also known as: ALDH8

NCBI Gene: 222 ENSG00000132746 UniProt: P48448

This protein oxidizes medium and long chain fatty aldehydes in lipid droplets into non-toxic fatty acids as part of aldehyde detoxification pathways. Mutations in ALDH3B2 cause autosomal recessive intellectual disability with delayed psychomotor development. The gene shows very low constraint against loss-of-function variants, suggesting haploinsufficiency is well-tolerated.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the aldehyde dehydrogenase family, a group of isozymes that may play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. The gene of this particular family member is over 10 kb in length. Altered methylation patterns at this locus have been observed in spermatozoa derived from patients exhibiting reduced fecundity. [provided by RefSeq, Aug 2017]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.66

LOEUF

Multiple*

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

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.66LOEUF

pLI 0.000

Z-score -0.47

OE 1.13 (0.78–1.66)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.13Z-score

OE missense 1.02 (0.92–1.14)

256 obs / 250.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.13 (0.78–1.66)

0≤0.351.4

Missense OE?1.02 (0.92–1.14)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 18 / 16.0Missense obs/exp: 256 / 250.2Syn Z: -0.60

Background carrier burden — how many people carry a rare variant somewhere in ALDH3B2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 51

547 rare PASS variants

Rare truncating (LoF)

1 in 570

101 rare PASS variants

Rare synonymous (reference)

1 in 87

202 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ALDH3B2. 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 56	1 in 580
South Asian	~43k	1 in 57	1 in 840
Remaining (unassigned)	~30k	1 in 36	1 in 630
European (Finnish)	~27k	1 in 190	≈ 1 in 13,000
Admixed American	~22k	1 in 35	1 in 1,700
African / African American	~21k	1 in 46	1 in 1,200
East Asian	~20k	1 in 69	1 in 530
Ashkenazi Jewish	~13k	1 in 180	1 in 1,400
Middle Eastern	~2,884	1 in 40	1 in 400

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): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓