PLCB4

phospholipase C beta 4, the group of C2 domain containing phospholipases|Phospholipases

Basic information

Region (hg38): 20:9067825-9504593

Links

ENSG00000101333NCBI:5332OMIM:600810HGNC:9059Uniprot:Q15147AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • auriculocondylar syndrome 1 (Strong), mode of inheritance: AD
  • auriculocondylar syndrome 2 (Moderate), mode of inheritance: Semidominant
  • auriculocondylar syndrome 2 (Definitive), mode of inheritance: AD
  • auriculocondylar syndrome (Supportive), mode of inheritance: AD
  • auriculocondylar syndrome 2 (Strong), mode of inheritance: AR
  • auriculocondylar syndrome 2 (Strong), mode of inheritance: AD
  • auriculocondylar syndrome 2 (Definitive), mode of inheritance: AD
  • auriculocondylar syndrome 2 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Auriculocondylar syndrome 2A; Auriculocondylar syndrome 2BADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Genitourinary; Gastrointestinal; Pulmonary16114046; 22560091; 23913798; 27007857; 28328130; 32201334; 35170830

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLCB4 gene.

  • Auriculocondylar syndrome 2 (5 variants)
  • Auriculocondylar syndrome 1 (5 variants)
  • not provided (2 variants)
  • Auriculocondylar syndrome (1 variants)
  • Inborn genetic diseases (1 variants)
  • Ocular melanocytosis;Uveal melanoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLCB4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
4
clinvar
16
clinvar
8
clinvar
28
missense
6
clinvar
4
clinvar
56
clinvar
9
clinvar
6
clinvar
81
nonsense
1
clinvar
1
start loss
0
frameshift
1
clinvar
1
clinvar
1
clinvar
3
inframe indel
0
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
1
clinvar
3
splice region
8
3
12
23
non coding
29
clinvar
9
clinvar
60
clinvar
98
Total 8 6 92 34 74

Highest pathogenic variant AF is 0.0000132

Variants in PLCB4

This is a list of pathogenic ClinVar variants found in the PLCB4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
20-9307832-AT-A Likely pathogenic (Mar 23, 2024)3342734
20-9307875-G-A Auriculocondylar syndrome 2 Benign (Jan 29, 2024)339552
20-9307876-C-A Inborn genetic diseases Uncertain significance (Sep 17, 2021)2380526
20-9307904-G-T Auriculocondylar syndrome 2 Uncertain significance (Jan 13, 2018)898788
20-9337160-A-C Inborn genetic diseases Uncertain significance (Sep 01, 2021)2387242
20-9338200-G-A Benign (May 14, 2021)1244492
20-9338886-C-T Auriculocondylar syndrome 2 Benign (Jan 12, 2018)339553
20-9338978-A-G Inborn genetic diseases Uncertain significance (Aug 02, 2022)2406190
20-9338996-A-C Inborn genetic diseases Uncertain significance (Jan 07, 2022)2270709
20-9362753-A-G Benign (May 15, 2021)1275561
20-9362934-C-A Malignant tumor of prostate Uncertain significance (-)161550
20-9362947-G-A Auriculocondylar syndrome 2 Benign (Jan 12, 2018)898789
20-9362969-A-G Inborn genetic diseases Uncertain significance (Feb 27, 2023)2489229
20-9362974-C-G not specified Uncertain significance (Dec 02, 2016)373682
20-9362974-C-T Long QT syndrome Likely benign (-)207904
20-9365464-G-T Likely pathogenic (Aug 03, 2016)382944
20-9365473-G-A Auriculocondylar syndrome 2 Benign/Likely benign (Jul 10, 2023)339554
20-9365521-A-AATC Likely benign (Aug 16, 2022)2104205
20-9365555-A-G Benign (May 18, 2021)1288956
20-9371208-C-T Auriculocondylar syndrome 2 Benign (Jan 13, 2018)339555
20-9371235-G-A Uncertain significance (Jan 08, 2022)2159043
20-9371245-G-A Auriculocondylar syndrome 2 Uncertain significance (Jan 13, 2018)339556
20-9371268-C-T PLCB4-related disorder Likely benign (Sep 04, 2019)3053813
20-9371285-C-G Inborn genetic diseases Uncertain significance (Apr 26, 2023)2540760
20-9372069-C-T Benign (May 14, 2021)1260941

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PLCB4protein_codingprotein_codingENST00000378501 36412480
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.000003041.001256740741257480.000294
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense3.573826350.6010.00003317945
Missense in Polyphen120265.560.451883253
Synonymous0.1342242270.9890.00001282081
Loss of Function5.552577.80.3210.00000419942

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004150.000415
Ashkenazi Jewish0.00009920.0000992
East Asian0.0002200.000109
Finnish0.0001860.000185
European (Non-Finnish)0.0001150.000114
Middle Eastern0.0002200.000109
South Asian0.001310.00131
Other0.0003270.000326

dbNSFP

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. This form has a role in retina signal transduction.;
Pathway
Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Platelet activation - Homo sapiens (human);Cortisol synthesis and secretion - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Inositol phosphate metabolism - Homo sapiens (human);Long-term potentiation - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Thyroid hormone synthesis - Homo sapiens (human);Long-term depression - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Gap junction - Homo sapiens (human);African trypanosomiasis - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human);Renin secretion - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Proton Pump Inhibitor Pathway, Pharmacodynamics;Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics;Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Alzheimers Disease;Chemokine signaling pathway;Splicing factor NOVA regulated synaptic proteins;Wnt Signaling Pathway;Signaling by GPCR;D-<i>myo</i>-inositol (1,4,5)-trisphosphate biosynthesis;Signal Transduction;GPCR GroupI metabotropic glutamate receptor;GPCR signaling-G alpha q;Inositol phosphate metabolism;Metabolism;phospholipases;D-<i>myo</i>-inositol-5-phosphate metabolism;superpathway of inositol phosphate compounds;Phosphatidylinositol phosphate metabolism;Synthesis of IP3 and IP4 in the cytosol;Inositol phosphate metabolism;PLC beta mediated events;G-protein mediated events;Opioid Signalling;G alpha (i) signalling events;G alpha (q) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

pRec
0.146

Intolerance Scores

loftool
0.679
rvis_EVS
-0.91
rvis_percentile_EVS
10.07

Haploinsufficiency Scores

pHI
0.123
hipred
Y
hipred_score
0.682
ghis
0.584

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.109

Gene Damage Prediction

AllRecessiveDominant
MendelianHighMediumHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Plcb4
Phenotype
behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype;

Gene ontology

Biological process
G protein-coupled receptor signaling pathway;lipid catabolic process;inositol trisphosphate biosynthetic process;intracellular signal transduction;inositol phosphate metabolic process;modulation of chemical synaptic transmission
Cellular component
nucleus;smooth endoplasmic reticulum;cytosol;postsynaptic density;dendrite;parallel fiber to Purkinje cell synapse;glutamatergic synapse
Molecular function
phosphatidylinositol phospholipase C activity;phospholipase C activity;calcium ion binding;protein binding