CYP4A22

Chr 1

cytochrome P450 family 4 subfamily A member 22

NCBI Gene: 284541 ENSG00000162365 UniProt: Q5TCH4

This cytochrome P450 enzyme catalyzes omega- and (omega-1)-hydroxylation of fatty acids such as laurate and palmitate but shows no activity towards arachidonic acid. The gene is not highly constrained against loss-of-function variants (pLI near zero, LOEUF 1.87), and no established Mendelian disease associations have been reported in the provided data.

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. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.87

Clinical Summary— CYP4A22

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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

73 VUS of 86 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.87LOEUF

pLI 0.000

Z-score -2.21

OE 1.48 (1.13–1.87)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.17Z-score

OE missense 1.19 (1.09–1.30)

352 obs / 295.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.48 (1.13–1.87)

0≤0.351.4

Missense OE?1.19 (1.09–1.30)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 37 / 25.1Missense obs/exp: 352 / 295.5Syn Z: 0.20

This gene — mechanism propensity

0.7035th %ile

GOF

0.6052th %ile

LOF

0.3259th %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

86 submitted variants in ClinVar

ClinVar

Classification Summary

VUS73

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	73	73
Likely Benign	4	4
Benign	0	0
Total	77	77

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 10) ClinVar copy-number / structural variants overlap CYP4A22 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →