CYP4Z1

Chr 1

cytochrome P450 family 4 subfamily Z member 1

Also known as: CYP4A20

NCBI Gene: 199974 ENSG00000186160 UniProt: Q86W10 OMIM: 618953

This enzyme catalyzes the hydroxylation and epoxidation of fatty acids, particularly lauric and myristic acids, and produces epoxyeicosatrienoic acid from arachidonic acid. CYP4Z1 mutations have not been established as a cause of human disease, and no clear inheritance pattern or clinical phenotype has been defined for this gene. The gene shows tolerance to loss-of-function variants (LOEUF 1.464), suggesting that complete loss of this enzyme may not cause severe developmental phenotypes.

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 gene is part of a cluster of cytochrome P450 genes on chromosome 1p33. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.46

Clinical Summary— CYP4Z1

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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

68 VUS of 84 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?

1.46LOEUF

pLI 0.000

Z-score -0.22

OE 1.05 (0.76–1.46)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.11Z-score

OE missense 0.98 (0.89–1.09)

260 obs / 265.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.05 (0.76–1.46)

0≤0.351.4

Missense OE?0.98 (0.89–1.09)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 25 / 23.8Missense obs/exp: 260 / 265.1Syn Z: 1.11

This gene — mechanism propensity

0.6744th %ile

GOF

0.5367th %ile

LOF

0.3455th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

84 submitted variants in ClinVar

ClinVar

Classification Summary

VUS68

Likely Benign8

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	68	0	68
Likely Benign	6	2	8
Benign	1	0	1
Total	75	2	77

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap CYP4Z1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →