ABCG2: the second transporter in the rosuvastatin story

What ABCG2 does

ABCG2 makes a pump, usually called BCRP, that sits in cell membranes in the gut and the liver and pushes certain drugs back out. For rosuvastatin the practical effect is on absorption and clearance: a weaker pump means more of the drug gets in and less of it leaves, so the same tablet produces higher blood levels. The gene has a second life outside pharmacology as a determinant of uric acid handling, which is why you may see it mentioned in the context of gout, but that is not what CPIC grades it for and not what Aimosti reports here.

The transporter function groups

The grading is short because the evidence is. CPIC recognises normal function, decreased function and poor function for ABCG2, driven mainly by one common variant, rs2231142, also written Q141K. One copy gives decreased function, two give poor function. There is no metabolizer scale here, because ABCG2 is a pump rather than an enzyme.

Medications where it matters

rosuvastatin (Crestor)

Rosuvastatin is the only drug in CPIC's ABCG2 guidance, and the recommendation is written for the pair of transporters rather than for this gene alone. The rows below assume a typical SLCO1B1 result. If your SLCO1B1 result is not typical, CPIC's advice for the pair changes. From a chip or a plain VCF the report's ABCG2 card quotes the row for the SLCO1B1 result your file gives; the gVCF and Deep Read cards quote the row for a typical SLCO1B1 and say so. The rosuvastatin page sets out both tables.

If your result is	Published CPIC guidance
Decreased Function	Per CPIC (A): "Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines."
Normal Function	Per CPIC (A): "Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines."
Poor Function	Per CPIC (A): "Prescribe ≤20mg as a starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. If dose >20mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., rosuvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391)."

Is this in your raw DNA file?

ABCG2 is part of the standard report from a chip export or a variant file as well as from aligned reads, because CPIC grades it on one position, rs2231142, and most consumer arrays type it. Some exports leave it out: we have seen MyHeritage, FamilyTreeDNA and Living DNA files with no row for it, and on those the card says the position was not on your array instead of calling the gene normal. A gVCF counts the position only where the file actually called it. A plain VCF cannot prove a missing position was covered, so a reference result from one carries that caveat. CPIC reads the two transporters together for rosuvastatin, so from a chip or a plain VCF the ABCG2 card quotes CPIC's row for the SLCO1B1 result read from the same file.

A genotyping chip reads only a few hundred thousand pre-selected positions, about 0.02% of your genome, chosen for common variation. It does not sequence the rest, so it cannot find the rare or novel pathogenic variants the clinical and carrier modules look for: a “no finding” from chip data means “this chip never looked”, far more so than with whole-genome sequencing. Chip data suits common-variant traits, pharmacogenomic tag SNPs, and haplogroup ancestry, not clinical or carrier screening.