CYP4A22

protein-coding

cytochrome P450 family 4 subfamily A 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 1p33. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

MANE transcript

NM_001010969.4

Inheritance

—

ClinVar variants

U:78B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.48

Max pathogenic AF

—

Genomic locus

chr1:47,137,435-47,149,727

External References & Databases

Ensembl (ENSG00000162365)

Transcript & Mutation Effects

hg38 • Region Span ~12.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CYP4A22 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 77

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001010969.4. 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						0
missense			74 clinvar	4 clinvar		78
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	78	4	0	82

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 67 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001010969.4	RefSeq	NP_001010969.2	12	MANE Select
ENST00000371891.8	Ensembl	ENSP00000360958.3	12	MANE Select
NM_001308102.2	RefSeq	NP_001295031.1	9	Standard
NM_001437457.1	RefSeq	NP_001424386.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fatty acid degradation - Homo sapiens (human)
Vascular smooth muscle contraction - Homo sapiens (human)
Oxidation by Cytochrome P450
Phase I - Functionalization of compounds
Metabolism of lipids

Biological Process

lipid hydroxylation
oxidation-reduction process
omega-hydroxylase P450 pathway

Molecular Function

iron ion binding
heme binding
arachidonic acid omega-hydroxylase activity
laurate hydroxylase activity
16-hydroxypalmitate dehydrogenase activity

Cellular Component

extracellular space
endoplasmic reticulum membrane
organelle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371891
Coding exons: 12
Length: 12307
Individuals with no LoFs: 125086
Homozygous LoFs: 3
Heterozygous LoFs: 659
Defined: 125748
p: 0.00264

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.17	352	295	1.19	0.0000159	3386
Missense (PolyPhen)		96	84.84	1.1315		1150
Synonymous	0.201	114	117	0.976	0.00000625	1020
Loss of Function	-2.21	37	25.1	1.48	0.00000123	268

Population LoF Frequency

Population	CAF	p-value	Status
African	0.016	0.016	notable
Latino/Admixed American	0.0021	0.0021	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.010	0.010	notable
Finnish	0.0031	0.0031	notable
European (Non-Finnish)	0.00044	0.00043	rare
South Asian	0.00059	0.00059	rare
Other	0.0012	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the omega- and (omega-1)-hydroxylation of various fatty acids such as laurate and palmitate. Shows no activity towards arachidonic acid and prostaglandin A1. Lacks functional activity in the kidney and does not contribute to renal 20-hydroxyeicosatetraenoic acid (20-HETE) biosynthesis. {ECO:0000269|PubMed:10860550, ECO:0000269|PubMed:15611369}.;

Recessive Scores

pRec: 0.182

Intolerance Scores

LoFtool: 0.871
RVIS EVS: 3.2
RVIS percentile EVS: 99.35

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0858

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High