PCYT1A

Chr 3AR

phosphate cytidylyltransferase 1A, choline

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

NCBI Gene: 5130 ENSG00000161217 UniProt: P49585 OMIM: 123695

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene belongs to the cytidylyltransferase family and is involved in the regulation of phosphatidylcholine biosynthesis. Mutations in this gene are associated with spondylometaphyseal dysplasia with cone-rod dystrophy. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.862 OMIM phenotypes

Clinical Summary— PCYT1A

🧬

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.

📋

ClinVar Variants

16 unique Pathogenic / Likely Pathogenic· 143 VUS of 326 total submissions

💊

Clinical Trials

4 active or recruiting trials — potential therapeutic options may be available

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?

0.86LOEUF

pLI 0.000

Z-score 2.06

OE 0.52 (0.33–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.64Z-score

OE missense 0.68 (0.60–0.79)

145 obs / 212.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.52 (0.33–0.86)

0≤0.351.4

Missense OE?0.68 (0.60–0.79)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

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

This gene — mechanism propensity

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

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

326 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic9

VUS143

Likely Benign131

Benign16

Conflicting7

Pathogenic

Likely Pathogenic

143

VUS

131

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	5	0	0	7
Likely Pathogenic	5	4	0	0	9
VUS	14	117	9	3	143
Likely Benign	0	11	41	79	131
Benign	0	2	10	4	16
Conflicting	—				7
Total	21	139	60	86	313

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

View in ClinVar →

87 pathogenic / likely-pathogenic (of 111) ClinVar copy-number / structural variants overlap PCYT1A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →