46,XY Disorders of Androgen Synthesis and Action

name: Androgen Synthesis and Action Disorders
display_name: 46,XY Disorders of Androgen Synthesis and Action
creation_date: "2026-06-13T00:00:00Z"
description: >-
  A group of 46,XY disorders of sex development in which the testis is normally
  determined but the androgen pathway downstream of it fails — either the
  biosynthesis of testosterone or its peripheral activation to the more potent
  dihydrotestosterone. The shared consequence is undervirilization of a 46,XY
  individual with functioning testes, distinguishing these disorders from the
  gonadal-determination defects (gonadal dysgenesis) that act at the level of the
  gonad itself.
grouping_basis:
- SHARED_MECHANISM
- SHARED_PATHWAY
grouping_rationale: >-
  Grouped on a shared biochemical pathway: each member is a 46,XY androgen-
  pathway defect and declares the androgen biosynthetic process. Members are kept
  as separate Disease entries because they act at different steps — testosterone
  biosynthesis (HSD17B3) versus peripheral conversion of testosterone to
  dihydrotestosterone (SRD5A2) — with characteristically different patterns of
  internal/external virilization and pubertal change. The criteria are NECESSARY:
  an androgen-pathway lesion is entailed by membership; the grouping is the
  androgen-synthesis/action complement of the separately curated gonadal-
  dysgenesis grouping (both narrowed out of the previously over-broad DSD union).
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0020040
      label: 46,XY disorder of sex development
    mapping_predicate: skos:narrowMatch
    mapping_source: MONDO
    mapping_justification: >-
      narrowMatch: this grouping is a mechanistic SUBSET of the MONDO 46,XY DSD
      class, restricted to the androgen-synthesis/action defects (excluding the
      46,XY gonadal-determination defects, which are captured by the separate
      Gonadal Dysgenesis grouping).
    consistency:
    - reference: MONDO
      consistent: CONSISTENT
      notes: >-
        Both listed members (HSD17B3 -> MONDO:0009916; SRD5A2 -> MONDO:0009923)
        are is-a descendants of MONDO:0020040.
membership_criteria:
- description: >-
    A member is a 46,XY disorder that perturbs the androgen biosynthetic process
    (testosterone synthesis or its activation to dihydrotestosterone).
  criteria_semantics: NECESSARY
  logic:
    criterion_predicate: HAS_BIOLOGICAL_PROCESS
    description: Involves the androgen biosynthetic process.
    biological_processes:
    - preferred_term: androgen biosynthetic process
      term:
        id: GO:0006702
        label: androgen biosynthetic process
members:
- member: 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      A defect of androgen synthesis: HSD17B3 cannot convert androstenedione to
      testosterone, causing undervirilization at birth with virilization at
      puberty as alternative pathways/isozymes generate testosterone.
    gene:
      preferred_term: HSD17B3
      term:
        id: hgnc:5212
        label: HSD17B3
- member: 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      A defect of peripheral androgen activation: SRD5A2 cannot convert
      testosterone to dihydrotestosterone, so external virilization fails
      prenatally (with virilization at puberty) while testosterone-dependent
      Wolffian structures still form — distinguishing it from a synthesis defect.
    gene:
      preferred_term: SRD5A2
      term:
        id: hgnc:11285
        label: SRD5A2
notes: >-
  A small but mechanistically tight union (testosterone synthesis vs DHT
  activation), split from the over-broad Disorders of Sex Development grouping
  alongside the Gonadal Dysgenesis grouping.