Palmoplantar keratoderma and erythrokeratodermas
Gene: POMP

POMP (proteasome maturation protein)
EnsemblGeneIds (GRCh38): ENSG00000132963
EnsemblGeneIds (GRCh37): ENSG00000132963
OMIM: 613386, Gene2Phenotype
POMP is in 7 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Promoting from Red to Green to match the latest rating on the GMS panels (R165/R166)
Created: 16 Jun 2025, 10:42 a.m. | Last Modified: 16 Jun 2025, 10:42 a.m.

Panel Version: 1.32

Created: 16 Jun 2025, 10:42 a.m.
Last Modified: 16 Jun 2025, 10:42 a.m.
Panel version: 1.32

Helen Brittain (Genomics England Curator)

Green List (high evidence)

Created: 10 Apr 2017, 9:10 a.m.

Panel version: 0.187

Rebecca Foulger (Genomics England curator)

Comment on list classification: Changed rating from Green to Red after discussion with Emma Baple and Ellen McDonagh, because the known pathogenic variant reported in all cases so far is in the 5'UTR of the POMP gene. Added 'curated variant list' tag, to flag this non-coding variant.
Created: 10 Apr 2017, 12:38 p.m.

Comment on mode of inheritance: Biallelic inheritance confirmed by OMIM and G2P.
Created: 10 Apr 2017, 8:24 a.m.

Added 'promoter' and 'non-coding-known-pathogenic' tags because the variant described in PMID:20226437 and PMID:27503413 is confirmed as pathogenic on ClinVar, and lies in the 5'UTR of the POMP gene.
Created: 3 Apr 2017, 2:03 p.m.

Palmoplantar keratoderma (PPK) is a phenotype of 'Keratosis linearis with ichthyosis congenita and sclerosing keratoderma, 601952 (KLICK syndrome). In 12 patients from 8 unrelated European families (from Spain, Italy, Netherlands, Sweden, Norway) with OMIM:601952, Dahlqvist et al. (2010, PMID: 20226437) identified homozygosity for a 1-bp deletion (-95delC) within a highly conserved 5' region of the POMP gene. Haplotype analysis suggested that the -95delC variant is a recurrent rather than a founder mutation.
Created: 3 Apr 2017, 12:58 p.m.

PMID:27503413 (Morice-Picard, 2017) report a young patient born from related parents, originally from the SW of France. The patient was presenting at birth with palmar keratoderma, and PPK was still present at the age of 11 years. Molecular analysis identified a homozygous 1-bp deletion in the 5′UTR non-coding region of the POMP gene (c.-95delC)- the same variation as reported in 20226437.
Created: 3 Apr 2017, 12:57 p.m.

Comment on list classification: Updated rating from Red to Green after discussion with Helen Brittain: PPK is a key feature of KLICK syndrome, and sufficient cases to support causation (PMID:20226437 and PMID:27503413). Note that all reported cases so far list the same 1bp deletion.
Created: 3 Apr 2017, 12:55 p.m.

Created: 3 Apr 2017, 2:03 p.m.

Panel version: 0.186

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
Radboud University Medical Center, Nijmegen

Phenotypes

Keratosis linearis with ichthyosis congenita and sclerosing keratoderma, OMIM:601952

Tags

promoter curated-variant-list non-coding-known-pathogenic

OMIM

613386

Clinvar variants

Variants in POMP

Penetrance

Complete

Publications

Panels with this gene

History Filter Activity

16 Jun 2025, Gel status: 3

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: pomp has been classified as Green List (High Evidence).

24 Jan 2024, Gel status: 1

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: POMP were changed from Keratosis linearis with ichthyosis congenita and sclerosing keratoderma, 601952 to Keratosis linearis with ichthyosis congenita and sclerosing keratoderma, OMIM:601952

11 Apr 2017, Gel status: 1