Unknown function

Alleles with unknown biochemical function

Unknown funtion means that the biochemical function of the allele is unknown or uncertain. There are at least four kind of alleles that have unknown biochemical function

• PGx alleles that are classified with Unknown function status by PharmGKB
• PGx alleles that are listed by PharmGKB, but has no functional status
• Unknown alleles with variants that cause changes to the protein, but which are not classified by PharmGKB
• Unknown alleles with variants that do not cause changes to the protein, and which are not classified by PharmGKB

The dosing recommendation for patients with an unknown biochemical function allele on at least one chromatid, is to follow the normal medication advice. This means that normal medication is recommended, even if the sister-chromatid has No function or Increased function.

This dosing recommendation is very conservative, and the question is whether the allele with Unknown function should rather be treated as a Normal function allele (thereby assigning modified dosing recommendations to e.g. Unknown function/No function-patients).

Alleles with normal biochemical function

Normal function means that the biochemical function of the allele is sufficiently close to the average that a normal medication recommendation can be used. Alleles with normal biochemical function are

• PGx alleles that are classified with Normal function status by PharmGKB
• alleles with no variants (which are usually contained in the PGx alleles that are classified by PharmGKB)

In addition, at least in the world of SNP-arrays, the definition of Normal function alleles and Unknown function alleles are overlapping

• Alleles that are not classified by PharmGKB have Normal function

In other words: the definitions Normal function and Unknown function are overlapping.

If we replace the Unknown function classification with Normal function, dosing recommendations for these patients have to be changed accordingly.