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…

Primary Disease Associations & Inheritance

Lipodystrophy, congenital generalized, type 5MIM #620680

Spondylometaphyseal dysplasia with cone-rod dystrophyMIM #608940

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · spondylometaphyseal dysplasia-cone-rod dystrophy syndrome · AR · ClinGen 2021

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.86

LOEUF

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in PCYT1A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 83

588 rare PASS variants

Rare truncating (LoF)

1 in 1,200

107 rare PASS variants

Rare synonymous (reference)

1 in 99

237 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PCYT1A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 1,600
South Asian	~43k	1 in 68	1 in 1,100
Remaining (unassigned)	~30k	1 in 66	1 in 320
European (Finnish)	~27k	1 in 180	1 in 680
Admixed American	~22k	1 in 84	1 in 620
African / African American	~21k	1 in 94	1 in 460
East Asian	~20k	1 in 98	1 in 2,600
Ashkenazi Jewish	~13k	1 in 250	1 in 1,400
Middle Eastern	~2,884	1 in 100	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 8 coding exons well covered in gnomAD exomes; exons 4, 6, 8, 9 marginal. Genomes: all 8.? see exons ↓