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
There is no explicit dosing recommendation for patients with an unknown biochemical function allele on at least one chromatid. This means that there is no special medication recommendation 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 (these "wildtype" alleles are usually explicitly classified as Normal function by PharmGKB, but not always)
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.