rs12934922 — BCO1 Arg267Ser

BCO1 Arg267Ser — When Carrots Are Not Enough

The BCO1 gene (formerly called BCMO1) encodes beta-carotene oxygenase 1¹¹ beta-carotene oxygenase 1
The enzyme that cleaves beta-carotene at its central double bond, producing two molecules of retinal (vitamin A aldehyde), the sole enzyme responsible for converting dietary beta-carotene into retinal²² retinal
The aldehyde form of vitamin A, which is then converted to retinol (storage form) or retinoic acid (active signaling form), the body's usable form of vitamin A. The rs12934922 variant causes an arginine-to-serine substitution at position 267 of the protein (Arg267Ser), reducing the enzyme's catalytic efficiency. This is one of two common coding variants in BCO1 — the other being rs7501331 (Ala379Val)³³ rs7501331 (Ala379Val)
The other major BCO1 coding variant, located in exon 8, which independently reduces conversion by about 32% — that together explain much of the genetic basis for the "poor converter" phenotype seen in up to 45% of the population.

The Mechanism

BCO1 is an iron-dependent dioxygenase⁴⁴ dioxygenase
An enzyme that incorporates both atoms of molecular oxygen into the substrate, requiring iron as a cofactor that symmetrically cleaves beta-carotene at its central 15,15' double bond. The Arg267Ser substitution (A-to-T at rs12934922) occurs in the enzyme's catalytic domain and reduces its ability to process beta-carotene. In vitro studies⁵⁵ In vitro studies
Leung WC et al. Two common SNPs in the gene encoding beta-carotene 15,15'-monoxygenase alter beta-carotene metabolism in female volunteers. FASEB J, 2009 of the recombinant double mutant protein (267Ser + 379Val) showed a 57% reduction in catalytic activity compared to the wild-type enzyme. In human volunteers, carriers of both variant alleles demonstrated a 69% reduction in beta-carotene conversion, as measured by the retinyl palmitate to beta-carotene ratio in triglyceride-rich lipoproteins after a beta-carotene dose.

The consequence is straightforward: people with reduced BCO1 activity accumulate more beta-carotene in their blood (sometimes visibly, as carotenodermia⁶⁶ carotenodermia
A yellowish skin discoloration caused by elevated blood carotenoid levels, harmless but sometimes confused with jaundice) while producing less retinol. This matters most for individuals who rely heavily on plant-based sources for their vitamin A — a concern for vegans, vegetarians, and populations in regions where animal-source foods are scarce.

The Evidence

The foundational study by Leung and colleagues⁷⁷ Leung and colleagues
Leung WC et al. Two common SNPs in the gene encoding beta-carotene 15,15'-monoxygenase alter beta-carotene metabolism in female volunteers. FASEB J, 2009 identified rs12934922 (R267S) and rs7501331 (A379V) as the two common coding variants in BCO1, with variant allele frequencies of 42% and 24% respectively. Female volunteers carrying the 379Val allele alone showed a 32% reduction in conversion (P=0.005), while those carrying both 267Ser and 379Val had a 69% reduction (P=0.001). Fasting beta-carotene concentrations increased by 160% and 240% respectively in these groups, directly reflecting the impaired conversion.

A large study by Hendrickson and colleagues⁸⁸ Hendrickson and colleagues
Hendrickson SJ et al. BCO1 SNPs in relation to plasma carotenoid and retinol concentrations in women of European descent. Am J Clin Nutr, 2012 in 2,344 women of European descent confirmed that the rs12934922 T allele was associated with significantly higher plasma beta-carotene levels (P = 1.1 x 10^-12), with a 48% difference between extreme genotype score quintiles. Notably, the variant did not affect plasma retinol concentrations, which are tightly regulated by liver stores and only drop when deficiency is severe.

Population-level analysis by Lietz et al.⁹⁹ Lietz et al.
Lietz G et al. SNPs upstream from the beta-carotene 15,15'-monoxygenase gene influence provitamin A conversion efficiency in female volunteers. J Nutr, 2012 revealed large inter-ethnic differences in BCO1 variant frequencies, with European populations carrying the T allele at ~44% frequency compared to ~14% in African and East Asian populations. This means the poor converter phenotype is substantially more common in people of European ancestry.

Practical Implications

The most important question is whether you need to adjust your vitamin A sources based on this variant. For people with one or two T alleles:

• Plant sources alone may not suffice. Beta-carotene from sweet potatoes, carrots, and leafy greens is converted less efficiently, meaning you may need to eat substantially more to achieve the same retinol yield — or include preformed vitamin A sources.

• Preformed vitamin A (retinol) from animal sources — liver, egg yolks, dairy, fatty fish — bypasses BCO1 entirely. These become more important for carriers, especially TT homozygotes.

• Vegetarians and vegans with this variant should be especially aware. Without animal sources, supplementation with preformed retinol (retinyl palmitate or retinyl acetate) may be worth discussing with a healthcare provider.

• Cooking and fat improve beta-carotene bioavailability. Eating carotenoid-rich foods cooked (not raw) and with a source of fat maximizes what your BCO1 enzyme can process.

• Plasma retinol testing is not useful for detecting marginal deficiency because the liver buffers levels until stores are nearly depleted. A better approach is to track symptoms (night vision difficulty, dry skin, frequent infections) and ensure adequate dietary intake.

Interactions

The rs12934922 variant interacts directly with rs7501331 (BCO1 A379V), the other major coding variant in the same gene. The combined effect is more than additive: carriers of T alleles at both positions show 69% reduced conversion versus 32% for rs7501331 T carriers alone. This suggests that the two amino acid changes compound the structural disruption of the enzyme's catalytic site. Because both variants are common (42% and 24% T allele frequency respectively), a meaningful proportion of people — estimated at 7-10% of Europeans — carry risk alleles at both positions. For these individuals, preformed vitamin A is particularly important.

Upstream regulatory variants (rs6564851, rs11645428, rs6420424) also independently reduce BCO1 expression by 48-59% and may further compound the coding variant effects, though the interaction has not been formally quantified in a single study.