CYP4F3

protein-coding

cytochrome P450 family 4 subfamily F member 3, the group of Cytochrome P450 family 4

Gene summary

This gene, CYP4F3, 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 protein localizes to the endoplasmic reticulum. The enzyme starts the process of inactivating and degrading leukotriene B4, a potent mediator of inflammation. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F8, is approximately 18 kb away. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Apr 2019]

Previous symbols:

LTB4H

MANE transcript

NM_000896.3

Inheritance

—

ClinVar variants

U:97B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.98

Max pathogenic AF

—

Genomic locus

chr19:15,640,897-15,662,825

External References & Databases

Ensembl (ENSG00000186529)

Transcript & Mutation Effects

hg38 • Region Span ~21.9 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 CYP4F3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 101

not providedTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000896.3. 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			1 clinvar	2 clinvar	1 clinvar	4
missense			95 clinvar	6 clinvar	2 clinvar	103
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	97	8	3	108

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000896.3	RefSeq	NP_000887.2	12	MANE Select
ENST00000221307.13	Ensembl	ENSP00000221307.6	12	MANE Select
NM_001199208.2	RefSeq	NP_001186137.1	12	Standard
NM_001199209.2	RefSeq	NP_001186138.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Arachidonic acid metabolism - Homo sapiens (human)
Etodolac Action Pathway
Ketoprofen Action Pathway
Ibuprofen Action Pathway
Rofecoxib Action Pathway

Biological Process

icosanoid metabolic process
leukotriene metabolic process
leukotriene B4 catabolic process
oxidation-reduction process

Molecular Function

monooxygenase activity
iron ion binding
heme binding
leukotriene-B4 20-monooxygenase activity
20-hydroxy-leukotriene B4 omega oxidase activity

Cellular Component

endoplasmic reticulum membrane
integral component of membrane
organelle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000221307
Coding exons: 12
Length: 21929
Individuals with no LoFs: 125414
Homozygous LoFs: 0
Heterozygous LoFs: 334
Defined: 125748
p: 0.00133

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.896	371	326	1.14	0.0000205	3415
Missense (PolyPhen)		97	82.279	1.1789		954
Synonymous	0.0598	129	130	0.993	0.00000788	1026
Loss of Function	0.0793	24	24.4	0.983	0.00000104	281

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0011	0.0010	notable
Latino/Admixed American	0.0039	0.0039	notable
Ashkenazi Jewish	0.0012	0.0012	notable
East Asian	0.00022	0.00022	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00092	0.00090	rare
South Asian	0.0016	0.0016	notable
Other	0.0013	0.0013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Isoform CYP4F3A: Catalyzes the omega-hydroxylation of leukotriene-B(4), a potent chemoattractant for polymorphonuclear leukocytes, it has low activity for arachidonic acid. {ECO:0000269|PubMed:11461919, ECO:0000269|PubMed:8486631}.;

Intolerance Scores

LoFtool: 0.328
RVIS EVS: 0.25
RVIS percentile EVS: 69.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.960

Gene Damage Prediction

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