CPIC standardized pharmacogenetic result terms

Contract

Report every pharmacogenetic result using ONLY the CPIC/PharmGKB consensus term vocabulary, spelled exactly. This applies whenever you translate a genotype, diplotype, or activity score into a phenotype call, or describe what an allele does. Do not invent, abbreviate, or fall back to legacy laboratory terms.

Rules

R1 — Metabolizer phenotype is exactly one of five terms. For a drug-metabolizing enzyme (CYP2D6, CYP2C19, CYP2C9, DPYD, TPMT, ...), the phenotype call is one of, and only one of:

• ultrarapid metabolizer
• rapid metabolizer
• normal metabolizer
• intermediate metabolizer
• poor metabolizer

The full-activity middle category is normal metabolizer. The historical term "extensive metabolizer" is retired and must never appear. "rapid metabolizer" is a distinct category sitting between ultrarapid and normal; it is not a synonym for ultrarapid.

R2 — Allele functional status is exactly one of six terms. An allele's function is one of:

• increased function
• normal function
• decreased function
• no function
• unknown function
• uncertain function

A complete loss-of-function allele is no function (never "null", "null allele", "nonfunctional", or "loss-of-function"). A partially reduced allele is decreased function (never "reduced function" or "partial function"). A gain-of-activity allele is increased function (never "gain-of-function"). The reference/fully-active allele is normal function (never "wild-type" or "fully functional"). Use unknown function when the allele is uncharacterized and uncertain function when the evidence conflicts — these are two distinct terms.

R3 — CYP2D6 activity score maps to phenotype at fixed band boundaries. Sum the per-allele activity values, then map:

• 0 -> poor metabolizer
• 0.25 to 1.0 -> intermediate metabolizer
• 1.25 to 2.25 -> normal metabolizer
• greater than 2.25 -> ultrarapid metabolizer

An activity score of exactly 1.0 is an intermediate metabolizer, not normal — this is the current consensus (a score of 1.0 was moved out of the normal band). The CYP2D610 allele contributes an activity value of 0.25 (a decreased-function allele), not 0.5.

R4 — Never substitute legacy or colloquial synonyms. "extensive metabolizer", "efficient/deficient metabolizer", "fast/slow metabolizer", "wild-type", "null allele", "loss-of-function" (as a status label), "reduced function", "gain-of-function", "hyperactive", "nonfunctional", and "inactive" are all non-conforming. Map each back to the R1/R2 terms.

R5 — Other result types (for completeness).

• Membrane transporters (e.g. SLCO1B1): increased function, normal function, decreased function,

poor function — note the transporter bucket is "poor function", not "poor metabolizer".

• High-risk genotype loci (e.g. HLA-B57:01, HLA-B15:02): report "positive" or "negative", never a

metabolizer phenotype and never "carrier" or "at-risk".

Worked examples

• CYP2D6 2/2 (two active copies, activity score 2.0):

BEFORE: "extensive metabolizer" / "EM" -> AFTER: "normal metabolizer"

• CYP2D6 3/6 (activity score 0):

BEFORE: "null metabolizer" / "non-metabolizer" -> AFTER: "poor metabolizer"

• CYP2D6 2/3 (activity score 1.0):

BEFORE: "normal metabolizer" -> AFTER: "intermediate metabolizer" (1.0 falls in the intermediate band)

• CYP2D6 2 plus a 2 duplication (activity score 3.0):

BEFORE: "rapid metabolizer" -> AFTER: "ultrarapid metabolizer"

• CYP2C19 2 allele:

BEFORE: "null" / "loss-of-function allele" -> AFTER: "no function"

• CYP2C19 17 allele:

BEFORE: "gain-of-function" -> AFTER: "increased function"

• CYP2D6 41 allele:

BEFORE: "reduced function" -> AFTER: "decreased function"

• The reference allele 1:

BEFORE: "wild-type" / "fully functional" -> AFTER: "normal function"

Edge cases

• rapid vs ultrarapid are two distinct phenotypes. CYP2C19 1/17 is a rapid metabolizer; 17/17 is an

ultrarapid metabolizer. Do not collapse them into one.

• normal metabolizer spans the whole full-activity band (CYP2D6 activity score 1.25 to 2.25), not only a

score of exactly 2.0.

• An allele with no published functional data is unknown function; one with conflicting functional

studies is uncertain function. Pick per the evidence — they are not interchangeable.

• Transporter results use a "poor function" bucket, never "poor metabolizer"; metabolizer terms are for

enzymes only.

• HLA and other high-risk loci are reported positive/negative, never as a metabolizer phenotype.

Do / Don't

• Do write "normal metabolizer"; don't write "extensive metabolizer".
• Do write "no function"; don't write "null", "null allele", or "nonfunctional".
• Do write "decreased function"; don't write "reduced function" or "partial function".
• Do write "increased function"; don't write "gain-of-function".
• Do write "normal function" for the reference allele; don't write "wild-type".
• Do classify a CYP2D6 activity score of 1.0 as intermediate metabolizer; don't call it normal.
• Do keep "rapid metabolizer" and "ultrarapid metabolizer" as separate categories; don't merge them.

Common mistakes

• Emitting "extensive metabolizer" for the normal category — the single most frequent error; the term is

retired.

• Labeling a deleted or inactive allele "null" instead of "no function".
• Writing "reduced function" instead of "decreased function".
• Calling a CYP2C19 1/17 result "ultrarapid" when it is "rapid metabolizer".
• Placing an activity score of 1.0 in the normal band (it is intermediate under the current consensus).
• Using "wild-type" or "fully functional" for the reference allele instead of "normal function".

Quick checklist

• ] Phenotype is one of: ultrarapid / rapid / normal / intermediate / poor metabolizer.
• ] No "extensive metabolizer" anywhere.
• ] Allele function is one of: increased / normal / decreased / no / unknown / uncertain function.
• ] Loss-of-function -> "no function"; partial -> "decreased function"; gain -> "increased function".
• ] CYP2D6 activity score 1.0 -> intermediate; greater than 2.25 -> ultrarapid.
• ] Reference allele -> "normal function", not "wild-type".