BDH1

Chr 3

3-hydroxybutyrate dehydrogenase 1

Also known as: BDH, SDR9C1

NCBI Gene: 622 ENSG00000161267 UniProt: Q02338 OMIM: 603063

The encoded protein is a mitochondrial membrane enzyme that catalyzes the interconversion of acetoacetate and (R)-3-hydroxybutyrate, the two major ketone bodies produced during fatty acid catabolism. Mutations cause 3-hydroxybutyric aciduria, an autosomal recessive metabolic disorder affecting ketone body metabolism. This gene is highly constrained against loss-of-function variants, indicating intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq

This gene encodes a member of the short-chain dehydrogenase/reductase gene family. The encoded protein forms a homotetrameric lipid-requiring enzyme of the mitochondrial membrane and has a specific requirement for phosphatidylcholine for optimal enzymatic activity. The encoded protein catalyzes the interconversion of acetoacetate and (R)-3-hydroxybutyrate, the two major ketone bodies produced during fatty acid catabolism. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.39

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.39LOEUF

pLI 0.000

Z-score 0.49

OE 0.86 (0.55–1.39)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.41Z-score

OE missense 0.92 (0.82–1.03)

212 obs / 229.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.86 (0.55–1.39)

0≤0.351.4

Missense OE?0.92 (0.82–1.03)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 12 / 14.0Missense obs/exp: 212 / 229.6Syn Z: -0.21

Background carrier burden — how many people carry a rare variant somewhere in BDH1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 93

524 rare PASS variants

Rare truncating (LoF)

1 in 1,000

81 rare PASS variants

Rare synonymous (reference)

1 in 120

224 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BDH1. 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 190	1 in 2,700
South Asian	~43k	1 in 97	1 in 1,900
Remaining (unassigned)	~30k	1 in 66	1 in 720
European (Finnish)	~27k	1 in 350	≈ 1 in 13,000
Admixed American	~22k	1 in 110	1 in 640
African / African American	~21k	1 in 120	1 in 550
East Asian	~20k	1 in 87	1 in 410
Ashkenazi Jewish	~13k	1 in 370	none seen
Middle Eastern	~2,884	1 in 93	≈ 1 in 2,900

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 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓