Mosaic skin disorders - deep sequencing

Gene: CARD14

Green List (high evidence)

Comment on list classification: There are 2 unrelated individuals reported with inflammatory linear verrucous epidermal nevus and mosaic variants in CARD14. 2 more mosaic cases have been reported without clinical or variant details. There is some functional evidence in cell cultures supporting the role of CARD14 in keratinocyte proliferation. Based on available evidence, this gene should be promoted to Green for Mosaic skin disorders - deep sequencing.

Created: 28 Nov 2025, 4:47 p.m. | Last Modified: 28 Nov 2025, 5:04 p.m.

Panel Version: 3.1

PMID: 34116062 Riachi et al., 2021
2 probands with heterozygous mosaic CARD14 variants, diagnosed with Inflammatory linear verrucous epidermal naevus (ILVEN).
Patient 1: c.356T > A, p.Met119Lys present in 20% of DNA. Variant not present in gnomAD v4. Same variant in a non-mosaic state caused pityriasis rubra pilaris (PMID: 28301045 Lwin et al., 2018).
Patient 2: c.277A>G, p.Lys93Glu present in 1% of DNA extracted from affected skin. Variant not in gnomAD v4.
Functional evidence: WST-1 proliferation assay showed a significant a proliferation rate increase in SVK14 cells transfected with the mutant CARD14 construct; ELISA showed a significant increase in NF-κB p65 subunit activity in patient 2 keratinocyte culture.

PMID: 38360177 Polubothu et al., 2024
2 patients with ILVEN with mosaic variants in CARD14 picked up on 250x WES - patient / variant details not specified.

PMID: 35853659 Atzmony et al., 2023
Patient 2 - female patient diagnosed with ILVEN, developed psoriasis vulgaris at 13 months; het for germline variant CARD14 c. 2044C>T, p.R682W; she also carried a post-zygotic variant in KRT10: c.467G>A, p.R156H. The CARD14 variant is very common (MAF = 0.01604 in gnomAD v4 - European population, total of 30 homozygotes reported). Mosaic KRT10 more likely to be causal?

This gene is associated with AD Pityriasis rubra pilaris MIM:173200 and AD Psoriasis 2 MIM:602723 in OMIM (accessed 28th Nov 2025).

Created: 28 Nov 2025, 4:03 p.m. | Last Modified: 28 Nov 2025, 5:02 p.m.

Panel Version: 3.1

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
inflammatory linear verrucous epidermal nevus, MONDO:0019318

Publications

• 34116062
• 35853659
• 38360177

Green List (high evidence)

Mosaic

Created: 31 Oct 2025, 2:06 p.m. | Last Modified: 31 Oct 2025, 2:06 p.m.

Panel Version: 3.1

Mode of inheritance
Other

Phenotypes
Inflammatory Linear Verrucous Epidermal Naevi (ILVEN)

Publications

• PMID: 34116062
• PMID: 38360177
• PMID: 35853659

Red List (low evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
ILVEN (submitted 2 cases)