BCO1

Chr 16AD

beta-carotene oxygenase 1

Also known as: BCDO, BCDO1, BCMO, BCMO1, BCO

NCBI Gene: 53630 ENSG00000135697 UniProt: Q9HAY6 OMIM: 605748

The encoded enzyme catalyzes the symmetric cleavage of beta-carotene into retinal, serving as a key step in vitamin A metabolism. Mutations cause hypercarotenemia and vitamin A deficiency with autosomal dominant inheritance. The gene shows minimal constraint against loss-of-function variants, suggesting tolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Vitamin A metabolism is important for vital processes such as vision, embryonic development, cell differentiation, and membrane and skin protection. The protein encoded by this gene is a key enzyme in beta-carotene metabolism to vitamin A. It catalyzes the oxidative cleavage of beta,beta-carotene into two retinal molecules. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Hypercarotenemia and vitamin A deficiency, autosomal dominantMIM #115300

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.18

LOEUF

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.18LOEUF

pLI 0.000

Z-score 0.87

OE 0.81 (0.57–1.18)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.90Z-score

OE missense 1.15 (1.05–1.25)

346 obs / 302.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.81 (0.57–1.18)

0≤0.351.4

Missense OE?1.15 (1.05–1.25)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 20 / 24.6Missense obs/exp: 346 / 302.1Syn Z: -1.88

Background carrier burden — how many people carry a rare variant somewhere in BCO1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 69

859 rare PASS variants

Rare truncating (LoF)

1 in 890

112 rare PASS variants

Rare synonymous (reference)

1 in 150

342 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BCO1. 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 100	1 in 870
South Asian	~43k	1 in 51	1 in 500
Remaining (unassigned)	~30k	1 in 63	1 in 1,200
European (Finnish)	~27k	1 in 130	1 in 1,300
Admixed American	~22k	1 in 74	1 in 3,700
African / African American	~21k	1 in 54	1 in 1,800
East Asian	~20k	1 in 110	1 in 2,500
Ashkenazi Jewish	~13k	1 in 170	1 in 2,200
Middle Eastern	~2,884	1 in 65	≈ 1 in 720

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