rs12934922 — BCO1 Arg267Ser

Reduces beta-carotene to retinol (vitamin A) conversion efficiency, contributing to the "poor converter" phenotype

See your personal result for BCO1

Upload your DNA data to find out which genotype you carry and what it means for you.

Upload your DNA data

Works with 23andMe, AncestryDNA, and other DNA test exports. Results in under 60 seconds.

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.

Nutrient Interactions

vitamin A (retinol) impaired_conversion
beta-carotene altered_metabolism

Genotype Interpretations

What each possible genotype means for this variant.

AA Full Converter Normal

Normal beta-carotene to vitamin A conversion

With the AA genotype at rs12934922, your BCO1 enzyme retains full catalytic activity at this position. The arginine at position 267 is the ancestral amino acid, preserved across species from fish to humans. Your ability to convert beta-carotene to retinal at this locus is unimpaired.

Note that overall beta-carotene conversion efficiency depends on multiple BCO1 variants. Even with AA here, the other major coding variant rs7501331 (Ala379Val) can independently reduce conversion by about 32% if you carry its T allele. The full picture requires looking at both variants together.

AT Reduced Converter Intermediate

Moderately reduced beta-carotene conversion

The heterozygous AT genotype produces a mix of wild-type (Arg267) and variant (Ser267) BCO1 enzyme. The overall conversion capacity is intermediate — reduced compared to AA but not as impaired as TT. In the Leung et al. 2009 study, the conversion reduction for heterozygous carriers was measurable but moderate, with the most significant impact seen when combined with the rs7501331 T allele.

Plasma beta-carotene levels tend to be slightly elevated in AT carriers compared to AA, reflecting the reduced conversion rate. This is not harmful — carotenoids are potent antioxidants — but it does mean less of the beta-carotene you eat becomes retinol.

TT Poor Converter Poor Converter

Significantly reduced beta-carotene to vitamin A conversion

The TT genotype means both copies of your BCO1 gene produce the Ser267 variant enzyme. In vitro studies show that when this is combined with the 379Val variant (from rs7501331), catalytic activity drops by 57%. In human volunteers, carriers of both coding variants showed a 69% reduction in beta-carotene conversion, with fasting beta-carotene concentrations elevated by up to 240% — reflecting carotenoid accumulation rather than conversion to retinal.

You may notice a slight yellow-orange tint to your skin (palms especially) if you eat large amounts of carotenoid-rich foods. This carotenodermia is harmless and simply reflects elevated circulating carotenoids. It is not jaundice and requires no treatment, but it is a visible indicator of reduced conversion.

Importantly, plasma retinol levels may appear normal even with impaired conversion, because the liver tightly regulates circulating retinol from stored reserves. Deficiency only manifests in blood tests once liver stores are substantially depleted — by which point symptoms (night blindness, dry skin, impaired immunity) may already be present.