PLD1

Chr 3AR

phospholipase D1

Also known as: CVDD, CVDP1

NCBI Gene: 5337 ENSG00000075651 UniProt: Q13393 OMIM: 602382

This gene encodes a phosphatidylcholine-specific phospholipase which catalyzes the hydrolysis of phosphatidylcholine in order to yield phosphatidic acid and choline. The enzyme may play a role in signal transduction and subcellular trafficking. Alternative splicing results in multiple transcript variants with both catalytic and regulatory properties. [provided by RefSeq, Sep 2011]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cardiac valvular dysplasia 1MIM #212093

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · PLD1-related congenital heart disease · AR · ClinGen 2024

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

0.88

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.88LOEUF

pLI 0.000

Z-score 2.36

OE 0.68 (0.53–0.88)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.18Z-score

OE missense 0.98 (0.92–1.05)

602 obs / 614.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.68 (0.53–0.88)

0≤0.351.4

Missense OE?0.98 (0.92–1.05)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 42 / 62.0Missense obs/exp: 602 / 614.8Syn Z: 0.96

Background carrier burden — how many people carry a rare variant somewhere in PLD1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 40

1,408 rare PASS variants

Rare truncating (LoF)

1 in 600

243 rare PASS variants

Rare synonymous (reference)

1 in 120

457 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PLD1. 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 58	1 in 640
South Asian	~43k	1 in 42	1 in 560
Remaining (unassigned)	~30k	1 in 32	1 in 510
European (Finnish)	~27k	1 in 87	1 in 5,300
Admixed American	~22k	1 in 35	1 in 410
African / African American	~21k	1 in 42	1 in 590
East Asian	~20k	1 in 39	1 in 670
Ashkenazi Jewish	~13k	1 in 240	≈ 1 in 6,100
Middle Eastern	~2,884	1 in 36	≈ 1 in 1,400

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): 12 of 26 coding exons well covered in gnomAD exomes; exon 6 poorly covered; exons 3, 4, 5, 8, 9 and 8 more marginal. Genomes: all 26.? see exons ↓