CYP4F22 Gene

The CYP4F22 gene (CYP4F22 is the acronym for Cytochrome P450 Family 4 Subfamily F Member 22) is a protein coding gene located on chromosome 19p13.12.

Diseases associated with CYP4F22 include:

• Ichthyosis, congenital, autosomal recessive 5 (ARCI5; OMIM: 604777) see below. Ichthyoses (overview)

They are detected in about 8% of all ACRI cases.

The CYP4F22 gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 family of proteins are monooxygenases that catalyze many reactions involved in drug metabolism and the synthesis of cholesterol, steroids, and other lipids. The CYP4F22 gene is part of a cluster of cytochrome P450 genes on chromosome 19 and encodes an enzyme thought to play a role in the 12(R)-lipoxygenase pathway.

Cytochrome P450 monooxygenase encoded by this gene is involved in epidermal ceramide biosynthesis. It hydroxylates the terminal carbon atom(omega hydroxylation) of ultralong-chain fatty acyls (C28-C36) prior to ceramide synthesis . Furthermore, the enzyme contributes to the synthesis of three classes of omega-hydroxy-ultralong chain fatty acyl ceramides with sphingosine, 6-hydroxysphingosine and phytosphingosine bases. These are important lipid components underlying the permeability barrier of the stratum corneum.

Lefevre et al (2006) identified7 different mutations in the CYP4F22 gene in 12 consanguineous families. These were 5 missense mutations and 2 deletions. The phenotype usually presented as lamellar ichthyosis with hyperlinearity of the palms and soles. The authors hypothesized that CYP4F22 plays a role in the 12(R)-lipoxygenase pathway that has been implicated in Sjögren-Larsson syndrome (OMIM: 270200) and congenital ichthyosis (612281) due to a mutation in the NIPAL4 gene (609383).

Lugassy et al (2008) identified a homozygous nonsense mutation in the CYP4F22 gene in 4 affected individuals from a large consanguineous Israeli drusen family with ARCI.

Lefevre et al (2006) identified homozygosity for a 1303C-T transition in exon 10 of the CYP4F22 gene in one French and in five Algerian consanguineous families with autosomal recessive congenital ichthyosis (ARCI5; 604777) of the lamellar type, resulting in a his435-to-tyr (H435Y) substitution in a highly conserved region of the protein.

1. Hotz A et al (2018) Mutation update for CYP4F22 variants associated with autosomal recessive congenital ichthyosis. Hum Mutat 39:1305-1313.
2. Lefevre C et al (2006) Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3. Hum Molec Genet 15: 767-776.
3. Lugassy J et al (2008) Rapid detection of homozygous mutations in congenital recessive ichthyosis. Arch Derm Res 300: 81-85.
4. Sayeb M et al (2019) A Tunisian family with a novel mutation in the gene CYP4F22 for lamellar ichthyosis and co-occurrence of hearing loss in a child due to mutation in the SLC26A4 gene. Int J Dermatol 58:1439-1443.