PCYT2

Chr 17AR

phosphate cytidylyltransferase 2, ethanolamine

Also known as: ET, SPG82

NCBI Gene: 5833ENSG00000185813UniProt: Q99447

This gene encodes an enzyme that catalyzes the formation of CDP-ethanolamine from CTP and phosphoethanolamine in the Kennedy pathway of phospholipid synthesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

Primary Disease Associations & Inheritance

Spastic paraplegia 82, autosomal recessiveMIM #618770
AR
166
ClinVar variants
32
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PCYT2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
32 Pathogenic / Likely Pathogenic· 106 VUS of 166 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.
0.70LOEUF
pLI 0.001
Z-score 2.62
OE 0.40 (0.24–0.70)
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.
1.73Z-score
OE missense 0.69 (0.61–0.78)
169 obs / 245.2 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.0.40 (0.24–0.70)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.61–0.78)
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.1.09
0≤1.21.6
LoF obs/exp: 9 / 22.4Missense obs/exp: 169 / 245.2Syn Z: -0.74

ClinVar Variant Classifications

166 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic11
VUS106
Likely Benign17
Benign10
Conflicting1
21
Pathogenic
11
Likely Pathogenic
106
VUS
17
Likely Benign
10
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
18
0
21
Likely Pathogenic
0
5
6
0
11
VUS
1
96
9
0
106
Likely Benign
0
8
1
8
17
Benign
0
0
9
1
10
Conflicting
—1
Total3110439166

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

View in ClinVar →

Protein Context — Lollipop Plot

PCYT2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PCYT2-related complex hereditary 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 82, autosomal recessive

MIM #618770

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Aging-rewired metabolic cues promote autophagy and senescence via DRAM1.
Yang J et al.·Autophagy
2025
Expanding the clinical and genetic spectrum of PCYT2-related disorders.
Vélez-Santamaría V et al.·Brain
2020
PCYT2 deficiency in Saarlooswolfdogs with progressive retinal, central, and peripheral neurodegeneration.
Christen M et al.·Mol Genet Metab
2024
Reply: Expanding the clinical and genetic spectrum of PCYT2-related disorders.
Vaz FM et al.·Brain
2020
Fat body phospholipid state dictates hunger-driven feeding behavior.
Kelly KP et al.·Elife
2022
Lipid remodeling in context of cellular senescence.
Tighanimine K·Biochimie
2024Review
Bi-allelic variants in CHKA cause a neurodevelopmental disorder with epilepsy and microcephaly.
Klöckner C et al.·Brain
2022
A coding and non-coding transcriptomic perspective on the genomics of human metabolic disease.
Timmons JA et al.·Nucleic Acids Res
2018
Role of Phosphatidylethanolamine Biosynthesis in Herpes Simplex Virus 1-Infected Cells in Progeny Virus Morphogenesis in the Cytoplasm and in Viral Pathogenicity In Vivo.
Arii J et al.·J Virol
2020
Acquisition of Drug Resistance in Basal Cell Nevus Syndrome Tumors through Basal to Squamous Cell Carcinoma Transition.
Jussila AR et al.·J Invest Dermatol
2024Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Downregulation of PCYT2 by increased portal pressure safeguards liver regeneration after partial hepatectomy.
Pu G et al.·Theranostics
2026🔓 Open Access
Homeostatic response of phospholipid pathways to PCYT2 deficiency and impaired de Novo synthesis of phosphatidylethanolamine.
Iraji R et al.·Sci Rep
2025🔓 Open Access
PCYT2 overexpression induces mitochondrial damage and promotes apoptosis in hepatocellular carcinoma cells.
Bei X et al.·PLoS One
2025🔓 Open Access
PCYT2 mediates ovarian epithelial cancer metastasis by regulating cell membrane fluidity through the AMPK/FOXO1 signalling pathway.
Chen H et al.·Sci Rep
2025🔓 Open Access
Epigenome-wide methylation analysis shows phosphonoethylamine alleviates aberrant DNA methylation in NASH caused by Pcyt2 deficiency.
Grapentine S et al.·PLoS One
2025🔓 Open Access
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