CYP4V2

Chr 4AR

cytochrome P450 family 4 subfamily V member 2

Also known as: BCD, CYP4AH1

CYP4V2 encodes a cytochrome P450 monooxygenase that catalyzes omega-hydroxylation of polyunsaturated fatty acids including docosahexaenoate (DHA) and eicosapentaenoate (EPA), contributing to retinal fatty acid homeostasis. Mutations cause Bietti crystalline corneoretinal dystrophy, an autosomal recessive condition affecting the eyes with characteristic crystalline deposits in the cornea and retina. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with its recessive inheritance pattern.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Bietti crystalline corneoretinal dystrophyMIM #210370
AR
3
Active trials
22
Pubs (1 yr)
298
P/LP submissions
13%
P/LP missense
1.03
LOEUF
LOF
Mechanism· G2P
Clinical SummaryCYP4V2
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Gene-Disease Validity (ClinGen)
Bietti crystalline corneoretinal dystrophy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
207 unique Pathogenic / Likely Pathogenic· 340 VUS of 774 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — CYP4V2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.03LOEUF
pLI 0.000
Z-score 1.42
OE 0.70 (0.491.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.12Z-score
OE missense 1.02 (0.931.12)
305 obs / 299.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.70 (0.491.03)
00.351.4
Missense OE1.02 (0.931.12)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 19 / 27.0Missense obs/exp: 305 / 299.1Syn Z: 0.92
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCYP4V2-related Bietti crystalline corneoretinal dystrophyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.75top 25%
GOF
0.6443th %ile
LOF
0.2873th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

774 submitted variants in ClinVar

Classification Summary

Pathogenic164
Likely Pathogenic43
VUS340
Likely Benign139
Benign46
Conflicting30
164
Pathogenic
43
Likely Pathogenic
340
VUS
139
Likely Benign
46
Benign
30
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
24
16
124
0
164
Likely Pathogenic
14
11
18
0
43
VUS
3
219
114
4
340
Likely Benign
0
4
60
75
139
Benign
0
4
37
5
46
Conflicting
30
Total4125435384762

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CYP4V2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
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