schema: eds-research/corpus/v1
category:
  id: genetics
  label: Genetics
  description: Confirmed genes for twelve EDS types and the search for genes behind hEDS, the one type without a known cause.
  order: 30
records:
  - id: gen-heds-no-confirmed-gene
    kind: finding
    title: hEDS is the only subtype without a confirmed molecular basis
    description: All twelve other types in the 2017 classification have known causative genes. hEDS, the most common type, has no confirmed gene.
    summary: All twelve other types in the 2017 classification have known causative genes. hEDS, the most common type, has no confirmed molecular basis, so it is diagnosed from clinical criteria alone under the 2017 classification.
    subtypes: [heds]
    status: established
    criteria_era: international-2017
    evidence:
      - stratum: clinical
        tier: consensus-statement
        source_ids: [source-36ad1cab53c4cea4f4b4]
      - stratum: clinical
        tier: expert-review
        source_ids: [source-1ad3f0edd57e0fab1524]
    reviewed_at: "2026-09-16"
    tags: [genetics]
  - id: gen-klk15-first-candidate
    kind: finding
    title: KLK15 is a candidate gene for hEDS, not yet a diagnostic test
    description: Exome sequencing of 200 people with hEDS found a recurrent KLK15 variant in several families. KLK15 is a candidate gene, not a diagnostic test.
    summary: Whole-exome sequencing of 200 people with hEDS by the Norris Lab found rare and low-frequency variants in 14 of the 15 kallikrein (KLK) genes, including a recurrent KLK15 variant (p.Gly226Asp) that segregated in multiple families. Mice carrying the variant showed hEDS features in tendons and heart valves. The Ehlers-Danlos Society says KLK genes are not on EDS genetic testing panels and hEDS remains a clinical diagnosis, and the authors say the study does not propose a diagnostic framework.
    date: "2025-08"
    date_precision: month
    subtypes: [heds]
    status: emerging
    criteria_era: international-2017
    evidence:
      - stratum: clinical
        tier: mechanistic-study
        source_ids: [source-ee867f99ac8808a4ef80]
      - stratum: gray
        tier: preprint
        source_ids: [source-daaa8e28125b9b3bb775]
        note: The 2024 preprint of the same study.
      - stratum: community
        tier: patient-org-synthesis
        source_ids: [source-bb268c000069896e8023]
        note: The society's June 2024 summary of the same study.
    corroboration: single-origin
    reviewed_at: "2026-09-16"
    reassess_by: "2026-12-16"
    people: [Russell Norris]
    organizations: [Medical University of South Carolina]
    tags: [genetics, frontier]
  - id: gen-hedge-study
    kind: program
    title: HEDGE is studying the genetics of 1,000 people with hEDS
    description: HEDGE is studying the genetics of 1,000 people with hEDS. In October 2025 the society expected first publications in late 2025 or early 2026.
    summary: HEDGE (Hypermobile Ehlers-Danlos Genetic Evaluation), listed among The Ehlers-Danlos Society's research programs, is studying the genetics of 1,000 people with hEDS. In October 2025 the society said it expected the first publications in late 2025 or early 2026, and that timelines may shift.
    subtypes: [heds, hsd]
    status: emerging
    criteria_era: international-2017
    evidence:
      - stratum: registry
        tier: registry-report
        source_ids: [source-3440a2b9d5d99c580d3a]
      - stratum: community
        tier: patient-org-synthesis
        source_ids: [source-bb268c000069896e8023]
        note: Both pages come from The Ehlers-Danlos Society.
    corroboration: single-origin
    reviewed_at: "2026-09-16"
    reassess_by: "2026-12-16"
    organizations: [The Ehlers-Danlos Society]
    tags: [genetics, registry, frontier]
  - id: gen-collagen-and-pathway-map
    kind: finding
    title: The 2017 classification groups EDS genes by the process they affect
    description: The 2017 classification groups the EDS genes by the process they affect, from collagen structure to the complement pathway, for research use.
    summary: "To serve research, the 2017 classification groups the EDS types with known genes by the process each gene affects: collagen primary structure and processing (COL5A1, COL5A2, COL3A1, COL1A1, COL1A2, ADAMTS2), collagen folding and cross-linking (PLOD1, FKBP14), the myomatrix, where muscle meets the extracellular matrix (TNXB, COL12A1), glycosaminoglycan biosynthesis (B4GALT7, B3GALT6, CHST14, DSE), the complement pathway (C1R, C1S), and intracellular processes (SLC39A13, ZNF469, PRDM5). hEDS is listed as unresolved."
    subtypes: [all-eds]
    status: established
    criteria_era: international-2017
    evidence:
      - stratum: clinical
        tier: consensus-statement
        source_ids: [source-36ad1cab53c4cea4f4b4]
      - stratum: clinical
        tier: expert-review
        source_ids: [source-be972ed50decef4cbf0b]
    reviewed_at: "2026-09-16"
    tags: [genetics]