CYP4F22

protein-coding

cytochrome P450 family 4 subfamily F member 22, the group of Cytochrome P450 family 4

Gene summary

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This 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. Mutations in this gene are the cause of ichthyosis lamellar type 3. [provided by RefSeq, Jul 2008]

MANE transcript

NM_173483.4

Inheritance

ClinVar variants

P:52U:95B:72

Top phenotype

Ichthyosis, congenital, autosomal recessive 5

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr19:15,508,525-15,552,317

External References & Databases

Ensembl (ENSG00000171954)

Transcript & Mutation Effects

hg38 • Region Span ~43.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

lamellar ichthyosisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017778

Submitter: Orphanet

autosomal recessive congenital ichthyosis 5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011485

Submitter: Labcorp Genetics (formerly Invitae)

autosomal recessive congenital ichthyosis 5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011485

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Ichthyosis, congenital, autosomal recessive 5AR

Manifestation: Dermatologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 16436457

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CYP4F22 variants in ClinVar

12 Conditions Cataloged

not providedTotal: 142

Autosomal recessive congenital ichthyosis 5Total: 95

Inborn genetic diseasesTotal: 59

CYP4F22-related disorderTotal: 18

Lamellar ichthyosisTotal: 16

not specifiedTotal: 16

Atopic eczemaTotal: 2

Ichthyosis and erythrokeratodermaTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173483.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				38 clinvar	2 clinvar	40
missense	16 clinvar	12 clinvar	92 clinvar	28 clinvar	4 clinvar	152
nonsense	6 clinvar					6
start loss						0
frameshift	7 clinvar	4 clinvar	1 clinvar			12
splice donor/acceptor (+/-2bp)	5 clinvar	2 clinvar	2 clinvar			9
Total	34	18	95	66	6	219

Highest pathogenic variant AF is 0.00013135247

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173483.4	RefSeq	NP_775754.2	12	MANE Select
ENST00000269703.8	Ensembl	ENSP00000269703.1	12	MANE Select
ENST00000601005.2	Ensembl	ENSP00000469866.1	12	Standard
ENST00000601005.3	Ensembl	ENSP00000469866.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Oxidation by Cytochrome P450
Metapathway biotransformation Phase I and II
Phase I - Functionalization of compounds
Metabolism of lipids
Synthesis of Leukotrienes (LT) and Eoxins (EX)

Biological Process

icosanoid metabolic process
oxidation-reduction process

Molecular Function

monooxygenase activity
iron ion binding
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
heme binding

Cellular Component

endoplasmic reticulum membrane
organelle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000269703
Coding exons: 12
Length: 43825
Individuals with no LoFs: 125665
Homozygous LoFs: 0
Heterozygous LoFs: 83
Defined: 125748
p: 0.000330

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.402	306	326	0.937	0.0000233	3449
Missense (PolyPhen)		148	155.25	0.95329		1657
Synonymous	0.642	119	128	0.928	0.00000807	1068
Loss of Function	2.42	13	26.4	0.492	0.00000140	295

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00022	0.00022	rare
Finnish	0.0013	0.0013	notable
European (Non-Finnish)	0.00033	0.00033	rare
South Asian	0.00016	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Disease: DISEASE: Ichthyosis, congenital, autosomal recessive 5 (ARCI5) [MIM:604777]: A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs. {ECO:0000269|PubMed:16436457}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.150

Intolerance Scores

LoFtool: 0.470
RVIS EVS: -0.37
RVIS percentile EVS: 28.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.256

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium