PCYT1A

Chr 3AR

phosphate cytidylyltransferase 1A, choline

Also known as: CCTA, CCTalpha, CGL5, CT, CTA, CTPCT, PCYT1, SMDCRD

The protein catalyzes the rate-limiting step in the CDP-choline pathway for phosphatidylcholine biosynthesis. Biallelic mutations cause autosomal recessive spondylometaphyseal dysplasia with cone-rod dystrophy and congenital generalized lipodystrophy type 5. Disease likely results from loss of function given the autosomal recessive inheritance pattern.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Lipodystrophy, congenital generalized, type 5MIM #620680
AR
Spondylometaphyseal dysplasia with cone-rod dystrophyMIM #608940
AR
3
Active trials
11
Pubs (1 yr)
112
P/LP submissions
9%
P/LP missense
0.86
LOEUF
LOF
Mechanism· G2P
Clinical SummaryPCYT1A
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Gene-Disease Validity (ClinGen)
spondylometaphyseal dysplasia-cone-rod dystrophy syndrome · 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.
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ClinVar Variants
100 unique Pathogenic / Likely Pathogenic· 162 VUS of 432 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.000
Z-score 2.06
OE 0.52 (0.330.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.64Z-score
OE missense 0.68 (0.600.79)
145 obs / 212.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.52 (0.330.86)
00.351.4
Missense OE0.68 (0.600.79)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 11 / 21.2Missense obs/exp: 145 / 212.0Syn Z: -0.52
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePCYT1A-related spondylometaphyseal dysplasia with cone-rod dystrophyLOFAR

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

DN
0.6743th %ile
GOF
0.6249th %ile
LOF
0.4039th %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

432 submitted variants in ClinVar

Classification Summary

Pathogenic91
Likely Pathogenic9
VUS162
Likely Benign132
Benign16
Conflicting8
91
Pathogenic
9
Likely Pathogenic
162
VUS
132
Likely Benign
16
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
5
86
0
91
Likely Pathogenic
3
4
2
0
9
VUS
8
116
35
3
162
Likely Benign
0
11
42
79
132
Benign
0
2
10
4
16
Conflicting
8
Total1113817586418

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

View in ClinVar →

Protein Context — Lollipop Plot

PCYT1A · protein map & ClinVar variants

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

Clinical Literature
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