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…

LOFmechanismADLOEUF 1.181 OMIM phenotype

Clinical Summary— BCO1

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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

102 VUS of 153 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 →

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

This gene — mechanism propensity

0.5772th %ile

GOF

0.6052th %ile

LOF

0.3843th %ile

The Badonyi & Marsh model scores gain-of-function highest, but genomic evidence most strongly supports loss-of-function (haploinsufficiency) as the primary mechanism.

LOF1 literature citation

Literature Evidence

LOFThe mutation was not identified in 60 control chromosomes. The findings were consistent with a loss-of-function mutation resulting in haploinsufficiency.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References

1.PMID 17951468 ↗

ClinVar Variant Classifications

153 submitted variants in ClinVar

ClinVar

Classification Summary

VUS102

Likely Benign13

Benign32

Conflicting1

102

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	102	0	0	102
Likely Benign	0	7	1	5	13
Benign	0	4	25	3	32
Conflicting	—				1
Total	0	113	26	8	148

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

View in ClinVar →

41 pathogenic / likely-pathogenic (of 78) ClinVar copy-number / structural variants overlap BCO1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →