PLCD1

Chr 3ADAR

phospholipase C delta 1

Also known as: NDNC3, PLC-III

NCBI Gene: 5333 ENSG00000187091 UniProt: P51178 OMIM: 602142

The protein catalyzes hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into second messengers diacylglycerol (DAG) and inositol triphosphate (IP3) for intracellular signal transduction. Mutations cause hereditary leukonychia (nonsyndromic congenital nail disorder), which can be inherited in either autosomal dominant or autosomal recessive patterns. The gene shows very low constraint to loss-of-function variation (pLI near zero), suggesting tolerance to protein-truncating variants.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the phospholipase C family. Phospholipase C isozymes play critical roles in intracellular signal transduction by catalyzing the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into the second messengers diacylglycerol (DAG) and inositol triphosphate (IP3). The encoded protein functions as a tumor suppressor in several types of cancer, and mutations in this gene are a cause of hereditary leukonychia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Nail disorder, nonsyndromic congenital, 3, (leukonychia)MIM #151600

ADAR

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Nail disorder, nonsyndromic congenital, 3, (leukonychia); no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.10

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.10LOEUF

pLI 0.000

Z-score 1.02

OE 0.83 (0.62–1.10)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.24Z-score

OE missense 0.97 (0.90–1.05)

445 obs / 459.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.83 (0.62–1.10)

0≤0.351.4

Missense OE?0.97 (0.90–1.05)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 33 / 40.0Missense obs/exp: 445 / 459.6Syn Z: 0.10

Background carrier burden — how many people carry a rare variant somewhere in PLCD1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 48

977 rare PASS variants

Rare truncating (LoF)

1 in 430

169 rare PASS variants

Rare synonymous (reference)

1 in 84

402 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PLCD1. 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 60	1 in 400
South Asian	~43k	1 in 46	1 in 580
Remaining (unassigned)	~30k	1 in 43	1 in 300
European (Finnish)	~27k	1 in 190	1 in 2,600
Admixed American	~22k	1 in 44	1 in 690
African / African American	~21k	1 in 56	1 in 410
East Asian	~20k	1 in 70	1 in 740
Ashkenazi Jewish	~13k	1 in 140	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 50	≈ 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): All 15 coding exons well covered in gnomAD exomes and genomes.? see exons ↓