Skip to content

IEMbase 0781: ENPP1-related Cole disease

Scope

Field Value
IEMbase ID 781
Nosology 16.3.13.01
Nosology code IEM0038
Gene ENPP1
External IDs OMIM:615522; ORPHA:324561
Generated mapping UNMAPPED
Candidate DisMech targets No exact local target; reject Arterial_Calcification_of_Infancy.yaml
Review date 2026-07-11

IEMbase phenotype signal

IEMbase labels this autosomal dominant record as ENPP1-related ectonucleotide pyrophosphatase-phosphodiesterase 1 dimerization deficiency, with alternate name Cole disease and abbreviation COLED. The phenotype signal is dominated by dermatologic and ectopic-calcification findings: hyperkeratotic papules, hypopigmented macules, punctate palmoplantar keratoderma, calcinosis cutis, and calcific tendinopathy.

DisMech phenotype coverage

Arterial_Calcification_of_Infancy.yaml contains extensive ENPP1 coverage, but that entry is a recessive generalized arterial calcification of infancy model. It represents biallelic ENPP1 loss of function, infantile arterial calcification and stenosis, PPi/FGF23/rickets biology, hearing loss, and survivor complications. It does not model dominant Cole disease or the dimerization-defect skin phenotype.

Concordance and completeness

Judgement: true local gap.

The shared ENPP1 gene is not enough to treat the GACI entry as coverage. The inheritance, disease entity, clinical distribution, and primary phenotype set are different: Cole disease is represented here as an autosomal dominant cutaneous/soft-tissue mineralization disorder, whereas the local ENPP1 target is an autosomal recessive infantile arterial calcification disorder.

Curation actions

  • Keep IEMbase 0781 unmapped for now; do not collapse Cole disease into ENPP1-related GACI.
  • Future curation should create a distinct ENPP1/Cole disease entry or subtype only if the project decides that dominant ENPP1 dimerization deficiency is in scope as a separate DisMech entity.
  • Preserve the IEMbase prompts for palmoplantar keratoderma, hypopigmented macules, hyperkeratotic papules, calcinosis cutis, and calcific tendinopathy.