CYP4V2

cytochrome P450 family 4 subfamily V member 2, the group of Cytochrome P450 family 4

Basic information

Region (hg38): 4:186191567-186213463

Links

ENSG00000145476 ∙ NCBI:285440 ∙ OMIM:608614 ∙ HGNC:23198 ∙ Uniprot:Q6ZWL3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bietti crystalline corneoretinal dystrophy (Strong), mode of inheritance: AR
• Bietti crystalline corneoretinal dystrophy (Supportive), mode of inheritance: AR
• Bietti crystalline corneoretinal dystrophy (Strong), mode of inheritance: AR
• Bietti crystalline corneoretinal dystrophy (Definitive), mode of inheritance: AR
• Bietti crystalline corneoretinal dystrophy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bietti crystalline corneoretinal dystrophy	AR	General	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	Ophthalmologic	5299874; 306693; 3493804; 2783846; 11001583; 15042513; 18398705; 19508456; 21385027; 21565171; 22087103; 22497028; 22605929; 22693542; 22772592; 23143451; 23221965; 23242590; 23538635
Subclinical manifestations have been described in heterozygous individuals

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP4V2 gene.

• not provided (32 variants)
• Bietti crystalline corneoretinal dystrophy (14 variants)
• Retinal dystrophy (8 variants)
• Retinitis pigmentosa (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP4V2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	65	5	74
missense	8	9	201	3	3	224
nonsense	8	2				10
start loss						0
frameshift	12	4				16
inframe indel			6			6
splice donor/acceptor (+/-2bp)	4	1	1			6
splice region	1		4	6	1	12
non coding	2	5	87	45	32	171
Total	34	21	299	113	40

Highest pathogenic variant AF is 0.0000526

Variants in CYP4V2

This is a list of pathogenic ClinVar variants found in the CYP4V2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-186191625-C-T		Corneal dystrophy • Bietti crystalline corneoretinal dystrophy	Uncertain significance (Jan 12, 2018)
4-186191646-C-T		Corneal dystrophy • Bietti crystalline corneoretinal dystrophy	Uncertain significance (Jan 13, 2018)
4-186191672-A-G		Corneal dystrophy • Bietti crystalline corneoretinal dystrophy	Benign (May 11, 2021)
4-186191678-C-T		Corneal dystrophy • Bietti crystalline corneoretinal dystrophy	Benign (May 11, 2021)
4-186191691-G-T		Corneal dystrophy • Bietti crystalline corneoretinal dystrophy	Uncertain significance (Jan 13, 2018)
4-186191693-GC-G		Bietti crystalline corneoretinal dystrophy • Corneal Dystrophy, Recessive	Likely benign (Jun 14, 2016)
4-186191696-A-G		Bietti crystalline corneoretinal dystrophy • Corneal dystrophy	Benign/Likely benign (Jan 13, 2018)
4-186191768-C-G		Corneal dystrophy • Bietti crystalline corneoretinal dystrophy	Uncertain significance (Jan 13, 2018)
4-186191802-C-G		Bietti crystalline corneoretinal dystrophy • Corneal dystrophy	Uncertain significance (Jan 12, 2018)
4-186191828-C-CGGGGCTCTGGCT			Uncertain significance (Jun 18, 2022)
4-186191832-G-T			Likely benign (Aug 05, 2024)
4-186191835-C-G			Likely benign (Aug 31, 2022)
4-186191837-G-C			Uncertain significance (Oct 28, 2022)
4-186191847-C-G			Likely benign (Mar 14, 2024)
4-186191847-C-T		Corneal dystrophy • Bietti crystalline corneoretinal dystrophy • Retinal dystrophy	Conflicting classifications of pathogenicity (Jan 29, 2025)
4-186191848-G-C			Uncertain significance (Mar 02, 2023)
4-186191857-A-G		Inborn genetic diseases	Uncertain significance (Dec 04, 2024)
4-186191860-C-G		Inborn genetic diseases	Uncertain significance (Oct 09, 2024)
4-186191860-C-T			Likely benign (Dec 31, 2019)
4-186191863-C-G		Inborn genetic diseases	Uncertain significance (Nov 11, 2024)
4-186191867-T-C		Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 11, 2024)
4-186191868-GT-G			Pathogenic (Aug 23, 2023)
4-186191870-G-A		Bietti crystalline corneoretinal dystrophy	Likely pathogenic (Feb 21, 2024)
4-186191884-G-A			Likely benign (May 27, 2022)
4-186191887-C-G		Corneal dystrophy • Bietti crystalline corneoretinal dystrophy • not specified • Retinal dystrophy	Benign (Feb 03, 2025)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP4V2	protein_coding	protein_coding	ENST00000378802	11	21937

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.20e-10	0.663	125576	0	172	125748	0.000684

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.121	305	299	1.02	0.0000166	3456
Missense in Polyphen		112	107.96	1.0374		1261
Synonymous	0.919	96	108	0.888	0.00000591	966
Loss of Function	1.42	19	27.0	0.705	0.00000129	311

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000976	0.000976
Ashkenazi Jewish	0.00	0.00
East Asian	0.000924	0.000925
Finnish	0.00172	0.00171
European (Non-Finnish)	0.000748	0.000747
Middle Eastern	0.000924	0.000925
South Asian	0.0000653	0.0000653
Other	0.000656	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Omega-hydroxylase that oxidizes medium-chain saturated fatty acids and polyunsaturated omega-3 fatty acids, and which plays a role in fatty acid and steroid metabolism in the eye (PubMed:19661213, PubMed:22772592). Catalyzes the omega- hydroxylation of medium-chain saturated fatty acids such as laurate, myristate and palmitate in an NADPH-dependent pathway. The substrate specificity is higher for myristate > laurate > palmitate (C14>C16>C12) (PubMed:19661213). Acts as a polyunsaturated omega-3 fatty acids hydroxylase by mediating oxidation of docosahexaenoate (DHA) to 22-hydroxydocosahexaenoate (PubMed:22772592). Also produces some 21-hydroxydocosahexaenoate. Also converts eicosapentaenoate (EPA) to 20- hydroxyeicosapentaenoate (20-OH-EPA) (PubMed:22772592). {ECO:0000269|PubMed:19661213, ECO:0000269|PubMed:22772592}.
• Pathway: Oxidation by Cytochrome P450;Metapathway biotransformation Phase I and II;Signaling by GPCR;Signal Transduction;Phase I - Functionalization of compounds;Endogenous sterols;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;The canonical retinoid cycle in rods (twilight vision);G alpha (i) signalling events;Visual phototransduction;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.272

Intolerance Scores

• loftool: 0.535
• rvis_EVS: 0.42
• rvis_percentile_EVS: 77.23

Haploinsufficiency Scores

• pHI: 0.170
• hipred: N
• hipred_score: 0.229
• ghis: 0.485

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.641

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cyp4v3
• Phenotype: vision/eye phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: retinoid metabolic process;visual perception;fatty acid omega-oxidation;sterol metabolic process;response to stimulus
• Cellular component: endoplasmic reticulum membrane;integral component of membrane
• Molecular function: monooxygenase activity;iron ion binding;oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen;heme binding