---
name: cpic-pharmacogenetic-terms
source: https://app.decimal.ai/s/cpic-pharmacogenetic-terms@1/SKILL.md
source_sha256: b44772fc8aba
---

# 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 CYP2D6*10 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-B*57:01, HLA-B*15:02): 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".