GeneBe

PLCD1

protein-coding

phospholipase C delta 1, the group of Phospholipases|C2 domain containing phospholipases|EF-hand domain containing

Gene summary

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]

MANE transcript

NM_006225.4

Inheritance

AR, AD

ClinVar variants

P:13U:162B:36

Top phenotype

Nail disorder, nonsyndromic congenital, 3

gnomAD constraint

pLI —, LoF o/e 0.83

Max pathogenic AF

—

Genomic locus

chr3:38,007,496-38,029,642

External References & Databases

Ensembl (ENSG00000187091)NCBI Gene (5333)OMIM (602142)HGNC:9060GenCCUniProt (P51178)AlphaFoldClinVar (PLCD1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~22.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

nonsyndromic congenital nail disorder 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0007900

Submitter: PanelApp Australia

nonsyndromic congenital nail disorder 3MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0007900

Submitter: PanelApp Australia

nonsyndromic congenital nail disorder 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0007900

Submitter: Labcorp Genetics (formerly Invitae)

nonsyndromic congenital nail disorder 3LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0007900

Submitter: Ambry Genetics

nonsyndromic congenital nail disorder 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0007900

Submitter: G2P

nonsyndromic congenital nail disorder 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0007900

Submitter: Labcorp Genetics (formerly Invitae)

nonsyndromic congenital nail disorder 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0007900

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Nail disorder, nonsyndromic congenital, 3AD/AR

Manifestation: Dermatologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 21665001Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLCD1 variants in ClinVar

5 Conditions Cataloged
not specifiedTotal: 166
not providedTotal: 30
PLCD1-related disorderTotal: 19
Nonsyndromic congenital nail disorder 3Total: 16
Primary degenerative dementia of the Alzheimer type, presenile onsetTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006225.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
3
clinvar
19
clinvar
4
clinvar
 26
missense
1
clinvar
2
clinvar
156
clinvar
11
clinvar
2
clinvar
 172
nonsense
2
clinvar
4
clinvar
 6
start loss
0
frameshift
3
clinvar
 3
splice donor/acceptor (+/-2bp)
1
clinvar
3
clinvar
 4
Total49162306211

Highest pathogenic variant AF is 0.00034692494

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_006225.4RefSeqNP_006216.215MANE Select
ENST00000334661.5EnsemblENSP00000335600.415MANE Select
NM_001130964.2RefSeqNP_001124436.115Standard
ENST00000463876.5EnsemblENSP00000430344.115Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Inositol phosphate metabolism - Homo sapiens (human)
  • AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
  • Thyroid hormone signaling pathway - Homo sapiens (human)
  • Calcium signaling pathway - Homo sapiens (human)
  • Phosphatidylinositol signaling system - Homo sapiens (human)

Biological Process

  • angiogenesis
  • phospholipid metabolic process
  • lipid catabolic process
  • inositol trisphosphate biosynthetic process
  • intracellular signal transduction

Molecular Function

  • phosphatidylinositol phospholipase C activity
  • calcium ion binding
  • protein binding
  • phosphatidylinositol-4,5-bisphosphate binding
  • GTPase activating protein binding

Cellular Component

  • cytoplasm
  • cytosol
  • plasma membrane
  • extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000463876
Coding exons
15
Length
22267
Individuals with no LoFs
125576
Homozygous LoFs
0
Heterozygous LoFs
172
Defined
125748
p
0.000684
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.2414454600.9680.00003145094
Missense (PolyPhen)110130.070.84571614
Synonymous0.1031921940.9910.00001321522
Loss of Function1.023340.00.8250.00000219426

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000430.00043rare
Latino/Admixed American0.000490.00049rare
Ashkenazi Jewish0.000100.000099rare
East Asian0.000990.00092rare
Finnish0.000190.00018rare
European (Non-Finnish)0.000930.00092rare
South Asian0.000650.00065rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. Essential for trophoblast and placental development.;
Disease
DISEASE: Nail disorder, non-syndromic congenital, 3 (NDNC3) [MIM:151600]: A nail disorder characterized by a white appearance of the nail plate (true leukonychia), the nail bed (pseudoleukonychia), or neither (apparent leukonychia). Leukonychia may involve all of the nail (leukonychia totalis) or only part of the nail (leukonychia partialis), or can appear as one or more transverse bands (leukonychia striata) or white spots (leukonychia punctata). {ECO:0000269|PubMed:21665001}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.151

Intolerance Scores

LoFtool
0.884
RVIS EVS
-0.85
RVIS percentile EVS
10.96

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.833

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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