CYP4B1

Chr 1

cytochrome P450 family 4 subfamily B member 1

Also known as: CYPIVB1, P-450HP

NCBI Gene: 1580 ENSG00000142973 UniProt: P13584 OMIM: 124075

The protein is a cytochrome P450 monooxygenase that localizes to the endoplasmic reticulum and oxidizes steroids, fatty acids, and xenobiotics as part of an NADPH-dependent electron transport pathway. This gene is highly constrained against loss-of-function variants, but no human diseases have been definitively associated with CYP4B1 mutations despite the protein's metabolic functions. The inheritance pattern for any potential disorders would likely be autosomal recessive given the gene's constraint profile.

OMIM ResearchSummary from RefSeq, UniProt

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 protein localizes to the endoplasmic reticulum. In rodents, the homologous protein has been shown to metabolize certain carcinogens; however, the specific function of the human protein has not been determined. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jan 2016]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.10

Clinical Summary— CYP4B1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

76 VUS of 103 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.10LOEUF

pLI 0.000

Z-score 1.19

OE 0.74 (0.51–1.10)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.21Z-score

OE missense 1.03 (0.94–1.14)

312 obs / 301.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.74 (0.51–1.10)

0≤0.351.4

Missense OE?1.03 (0.94–1.14)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 18 / 24.3Missense obs/exp: 312 / 301.8Syn Z: -0.40

This gene — mechanism propensity

0.75top 25%

GOF

0.6639th %ile

LOF

0.2581th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

103 submitted variants in ClinVar

ClinVar

Classification Summary

VUS76

Likely Benign6

Benign8

Conflicting1

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	76	0	0	76
Likely Benign	0	3	0	3	6
Benign	1	5	1	1	8
Conflicting	—				1
Total	1	84	1	4	91

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

View in ClinVar →

7 pathogenic / likely-pathogenic (of 9) ClinVar copy-number / structural variants overlap CYP4B1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →