PCYT2

Chr 17AR

phosphate cytidylyltransferase 2, ethanolamine

Also known as: ET, SPG82

NCBI Gene: 5833 ENSG00000185813 UniProt: Q99447 OMIM: 602679

This enzyme catalyzes the formation of CDP-ethanolamine from CTP and phosphoethanolamine in the Kennedy pathway, which is essential for synthesizing phosphatidylethanolamine, a major membrane phospholipid. Mutations cause spastic paraplegia 82, an autosomal recessive disorder affecting the corticospinal tracts and causing progressive lower limb spasticity. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.702), suggesting some tolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.701 OMIM phenotype

Clinical Summary— PCYT2

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

11 unique Pathogenic / Likely Pathogenic· 103 VUS of 154 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?

0.70LOEUF

pLI 0.001

Z-score 2.62

OE 0.40 (0.24–0.70)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.73Z-score

OE missense 0.69 (0.61–0.78)

169 obs / 245.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.24–0.70)

0≤0.351.4

Missense OE?0.69 (0.61–0.78)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 9 / 22.4Missense obs/exp: 169 / 245.2Syn Z: -0.74

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitivePCYT2-related complex hereditary spastic paraplegiaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.7132th %ile

GOF

0.75top 25%

LOF

0.2775th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

154 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic8

VUS103

Likely Benign18

Benign9

Conflicting1

Pathogenic

Likely Pathogenic

103

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	1	0	0	3
Likely Pathogenic	2	5	1	0	8
VUS	1	98	4	0	103
Likely Benign	0	8	1	9	18
Benign	0	0	8	1	9
Conflicting	—				1
Total	5	112	14	10	142

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap PCYT2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →