ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000017.10) (NC_000017.11)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Changes in CARD14 have been associated with pityriasis rubra pilaris (PRP). Although most cases of PRP are simplex cases, familial cases demonstrate autosomal-dominant inheritance with an early age of onset, incomplete penetrance, and variable expressivity. Changes in CARD14 have also been reported in psoriasis susceptibility 2 (PSORS2). Fuchs-Telem et al. (2012) (PMID: 22703878) described three mutations ascertained in 4 unrelated families with PRP. Immunostaining for CARD14 on skin biopsies from mutation-positive, PRP-affected individuals revealed increased staining for CARD14 amongst affected individuals compared to wild-type. Similarly, Jordan et al. (2012) discuss missense mutations identified amongst individuals with PSORS2, and propose a mechanism by which "rare gain-of-function mutations in CARD14 initiate a process that includes inflammatory cell recruitment by keratinocytes. This perpetuates a vicious cycle of epidermal inflammation and regeneration, a cycle which is the hallmark of psoriasis." (PMID: 22521418).

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity