Genetics
Confirmed genes for twelve EDS types and the search for genes behind hEDS, the one type without a known cause.
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.
KLK15 is a candidate gene for hEDS, not yet a diagnostic test
findingevidence: emergingone underlying sourceWhole-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.
HEDGE is studying the genetics of 1,000 people with hEDS
research programevidence: emergingone underlying sourceHEDGE (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.
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.