CYP2U1

Chr 4AR

cytochrome P450 family 2 subfamily U member 1

Also known as: P450TEC, SPG49, SPG56

NCBI Gene: 113612ENSG00000155016UniProt: Q7Z449

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 enzyme is a hydroxylase that metabolizes arachidonic acid, docosahexaenoic acid, and other long chain fatty acids. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Spastic paraplegia 56, autosomal recessiveMIM #615030
AR
370
ClinVar variants
64
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CYP2U1
🧬
Gene-Disease Validity (ClinGen)
hereditary spastic paraplegia · 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.
📋
ClinVar Variants
64 Pathogenic / Likely Pathogenic· 170 VUS of 370 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.75LOEUF
pLI 0.001
Z-score 2.39
OE 0.41 (0.24–0.75)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.99Z-score
OE missense 0.83 (0.75–0.93)
233 obs / 279.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.41 (0.24–0.75)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.75–0.93)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 8 / 19.3Missense obs/exp: 233 / 279.8Syn Z: 0.64

ClinVar Variant Classifications

370 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic23
VUS170
Likely Benign95
Benign19
Conflicting22
41
Pathogenic
23
Likely Pathogenic
170
VUS
95
Likely Benign
19
Benign
22
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
7
17
0
41
Likely Pathogenic
8
8
7
0
23
VUS
2
159
7
2
170
Likely Benign
0
6
16
73
95
Benign
0
2
17
0
19
Conflicting
—22
Total271826475370

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

View in ClinVar →

Protein Context — Lollipop Plot

CYP2U1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CYP2U1-related spastic paraplegia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spastic paraplegia 56, autosomal recessive

MIM #615030

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Diagnostic journey and genetic analysis of a novel homozygous CYP2U1 mutation causing autosomal recessive spastic paraplegia type 56 (SPG56) in a consanguineous family.
Yu HP et al.·BMC Neurol
2025
Implication of folate deficiency in CYP2U1 loss of function.
Pujol C et al.·J Exp Med
2021
CYP2U1 activity is altered by missense mutations in hereditary spastic paraplegia 56.
Durand CM et al.·Hum Mutat
2018
Pseudoxanthoma elasticum overlaps hereditary spastic paraplegia type 56.
Legrand A et al.·J Intern Med
2021
Macular Dystrophy with Bilateral Macular Telangiectasia Related to the CYP2U1 Pathogenic Variant Assessed with Multimodal Imaging Including OCT-Angiography.
El Matri K et al.·Genes (Basel)
2021Case report
Pigmentary degenerative maculopathy as prominent phenotype in an Italian SPG56/CYP2U1 family.
Leonardi L et al.·J Neurol
2016Case report
Mutations in CYP2U1, DDHD2 and GBA2 genes are rare causes of complicated forms of hereditary spastic paraparesis.
Citterio A et al.·J Neurol
2014
Inborn errors of metabolism in the biosynthesis and remodelling of phospholipids.
Wortmann SB et al.·J Inherit Metab Dis
2015Review
Rare novel CYP2U1 and ZFYVE26 variants identified in two Pakistani families with spastic paraplegia.
Bibi F et al.·J Neurol Sci
2020Case report
[Analysis of CYP2U1 gene variants in a child with Hereditary spastic paraplegia type 56].
Zhang G et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2023Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools