PLCG2 phospholipase C gamma 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PLCG2provided by HGNC
Official Full Name: phospholipase C gamma 2provided by HGNC
Primary source: HGNC:HGNC:9066
See related: Ensembl:ENSG00000197943 MIM:600220; AllianceGenome:HGNC:9066
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FCAS3; APLAID; PLC-IV; PLC-gamma-2
Summary: The protein encoded by this gene is a transmembrane signaling enzyme that catalyzes the conversion of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to 1D-myo-inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) using calcium as a cofactor. IP3 and DAG are second messenger molecules important for transmitting signals from growth factor receptors and immune system receptors across the cell membrane. Mutations in this gene have been found in autoinflammation, antibody deficiency, and immune dysregulation syndrome and familial cold autoinflammatory syndrome 3. [provided by RefSeq, Mar 2014]
Expression: Broad expression in lymph node (RPKM 20.0), spleen (RPKM 12.3) and 21 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16q23.3

Exon count:: 35

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (81739041..81962685)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (87801375..88026424)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (81772646..81996290)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants.
Title: PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants.
Human PLCG2 haploinsufficiency results in a novel natural killer cell immunodeficiency.
Title: Human PLCG2 haploinsufficiency results in a novel natural killer cell immunodeficiency.
The hypermorphic PLCgamma2 S707Y variant dysregulates microglial cell function - Insight into PLCgamma2 activation in brain health and disease, and opportunities for therapeutic modulation.
Title: The hypermorphic PLCγ2 S707Y variant dysregulates microglial cell function - Insight into PLCγ2 activation in brain health and disease, and opportunities for therapeutic modulation.
A novel gain-of-function missense variant in PLCG2 associated with autoinflammation and hypergammaglobulinaemia.
Title: A novel gain-of-function missense variant in PLCG2 associated with autoinflammation and hypergammaglobulinaemia.
Golgi retention and oncogenic KIT signaling via PLCgamma2-PKD2-PI4KIIIbeta activation in gastrointestinal stromal tumor cells.
Title: Golgi retention and oncogenic KIT signaling via PLCγ2-PKD2-PI4KIIIβ activation in gastrointestinal stromal tumor cells.
BTK and PLCG2 remain unmutated in one-third of patients with CLL relapsing on ibrutinib.
Title: BTK and PLCG2 remain unmutated in one-third of patients with CLL relapsing on ibrutinib.
Carriers of the p.P522R variant in PLCgamma2 have a slightly more responsive immune system.
Title: Carriers of the p.P522R variant in PLCγ2 have a slightly more responsive immune system.
The P522R protective variant of PLCG2 promotes the expression of antigen presentation genes by human microglia in an Alzheimer's disease mouse model.
Title: The P522R protective variant of PLCG2 promotes the expression of antigen presentation genes by human microglia in an Alzheimer's disease mouse model.
Heterozygous expression of the Alzheimer's disease-protective PLCgamma2 P522R variant enhances Abeta clearance while preserving synapses.
Title: Heterozygous expression of the Alzheimer's disease-protective PLCγ2 P522R variant enhances Aβ clearance while preserving synapses.
PLCG2 is associated with the inflammatory response and is induced by amyloid plaques in Alzheimer's disease.
Title: PLCG2 is associated with the inflammatory response and is induced by amyloid plaques in Alzheimer's disease.

Submit: New GeneRIF Correction See all GeneRIFs (77)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation MedGen: C3553961 OMIM: 614878 GeneReviews: Not available	Compare labs
Familial cold autoinflammatory syndrome 3 MedGen: C3280914 OMIM: 614468 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome-wide interaction study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan. EBI GWAS Catalog EBI GWAS CatalogPubMed
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 envelope glycoproteins gp120 and gp160 directly and specifically impair the CD3/TcR-mediated activation of phospholipase C (PLC) via the CD4 molecule in uninfected T cells	PubMed
Pr55(Gag)	gag	SPRY2 interactions with PI(4,5)P2 and PLCgamma allow it to influence HIV-1 Gag release through interference with PI(4,5)P2 dynamics	PubMed
	gag	Phospholipase C-gamma is required for HIV-1 Gag release in the presence or absence of TSG101 binding	PubMed
Tat	tat	Phospholipase C/protein kinase C pathway-dependent phosphorylation of p44/42 and JNK MAP kinases is partially involved in IL-1beta induction by HIV-1 Tat	PubMed
	tat	HIV-1 Tat induces release of calcium and TNF-alpha production, an effect mediated at least in part by activation of phospholipase C	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:633458 (e-PCR)
- UniSTS:158510

SHGC-148982 (e-PCR)
- UniSTS:176719

RH68327 (e-PCR)
- UniSTS:8578

RH17426 (e-PCR)
- UniSTS:54421

SHGC-149548 (e-PCR)
- UniSTS:177070

D16S696 (e-PCR)
- UniSTS:149692

SHGC-154149 (e-PCR)
- UniSTS:182983

GDB:386186 (e-PCR)
- UniSTS:157145

SHGC-60970 (e-PCR)
- UniSTS:44012

RH65041 (e-PCR)
- UniSTS:88565

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables phosphatidylinositol phospholipase C activity	IBA Inferred from Biological aspect of Ancestor more info
enables phosphatidylinositol phospholipase C activity	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol phospholipase C activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables phosphatidylinositol phospholipase C activity	TAS Traceable Author Statement more info
enables phospholipase C activity	TAS Traceable Author Statement more info
enables phosphorylation-dependent protein binding	IEA Inferred from Electronic Annotation more info
enables phosphotyrosine residue binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables scaffold protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell activation	IDA Inferred from Direct Assay more info	PubMed
involved_in B cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in B cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in B cell receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in B cell receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in B cell receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in Fc-epsilon receptor signaling pathway	TAS Traceable Author Statement more info
involved_in T cell receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in Wnt signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in antifungal innate immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in calcium-mediated signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in calcium-mediated signaling	NAS Non-traceable Author Statement more info	PubMed
involved_in cell activation	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to calcium ion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to lectin	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to lipid	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in follicular B cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in inositol trisphosphate biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in intracellular signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in lipopolysaccharide-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in macrophage activation involved in immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of programmed cell death	IEA Inferred from Electronic Annotation more info
involved_in phosphatidylinositol biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in phosphatidylinositol metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in phosphatidylinositol-mediated signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in phospholipid catabolic process	IEA Inferred from Electronic Annotation more info
involved_in platelet activation	TAS Traceable Author Statement more info
acts_upstream_of_or_within positive regulation of DNA-binding transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of DNA-binding transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of I-kappaB phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of MAPK cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of NF-kappaB transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of NLRP3 inflammasome complex assembly	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of calcium-mediated signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cell cycle G1/S phase transition	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of dendritic cell cytokine production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of epithelial cell migration	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of positive regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-10 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-12 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-2 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-23 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-6 production	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of positive regulation of macrophage cytokine production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of neuroinflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of peptidyl-tyrosine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of phagocytosis, engulfment	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of positive regulation of reactive oxygen species biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of receptor internalization	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of tumor necrosis factor production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of type I interferon production	IEA Inferred from Electronic Annotation more info
involved_in programmed cell death	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of calcineurin-NFAT signaling cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of canonical NF-kappaB signal transduction	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of regulation of lipid metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in release of sequestered calcium ion into cytosol	IBA Inferred from Biological aspect of Ancestor more info
involved_in release of sequestered calcium ion into cytosol	IDA Inferred from Direct Assay more info	PubMed
involved_in response to axon injury	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to yeast	ISS Inferred from Sequence or Structural Similarity more info
involved_in stimulatory C-type lectin receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in stimulatory C-type lectin receptor signaling pathway	TAS Traceable Author Statement more info
involved_in toll-like receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in intracellular vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in membrane raft	ISS Inferred from Sequence or Structural Similarity more info
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
is_active_in ruffle membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in ruffle membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2

Names: phosphoinositide phospholipase C-gamma-2; phospholipase C, gamma 2 (phosphatidylinositol-specific); phospholipase C-IV

NP_001412678.1

EC 3.1.4.11

NP_001412679.1

EC 3.1.4.11

NP_001412680.1

EC 3.1.4.11

NP_002652.2

EC 3.1.4.11

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_032019.2 RefSeqGene

Range

45162..226198

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_376

mRNA and Protein(s)

NM_001425749.1 → NP_001412678.1 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2

Status: REVIEWED

Source sequence(s)

AC092142, AC098966, AC099524

UniProtKB/Swiss-Prot

D3DUL3, P16885, Q3ZTS2, Q59H45, Q969T5

Related

ENSP00000520638.1, ENST00000565054.7
NM_001425750.1 → NP_001412679.1 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2

Status: REVIEWED

Source sequence(s)

AC092142, AC098966, AC099524

UniProtKB/Swiss-Prot

D3DUL3, P16885, Q3ZTS2, Q59H45, Q969T5

Related

ENSP00000520637.1, ENST00000697580.2
NM_001425751.1 → NP_001412680.1 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2

Status: REVIEWED

Source sequence(s)

AC092142, AC098966, AC099524

UniProtKB/Swiss-Prot

D3DUL3, P16885, Q3ZTS2, Q59H45, Q969T5
NM_002661.5 → NP_002652.2 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2

See identical proteins and their annotated locations for NP_002652.2

Status: REVIEWED

Source sequence(s)

AB208914, AC092142, BC007565, BP351485, BX504887, DB456860

Consensus CDS

CCDS42204.1

UniProtKB/Swiss-Prot

D3DUL3, P16885, Q3ZTS2, Q59H45, Q969T5

UniProtKB/TrEMBL

A0A8V8TMG4

Related

ENSP00000482457.1, ENST00000564138.6

Conserved Domains (9) summary

cd00275
Location:1061 → 1187

C2_PLC_like; C2 domain present in Phosphoinositide-specific phospholipases C (PLC)

cd08592
Location:311 → 458

PI-PLCc_gamma; Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma

cd09932
Location:641 → 744

SH2_C-SH2_PLC_gamma_like; C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma

cd10341
Location:527 → 627

SH2_N-SH2_PLC_gamma_like; N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma

cd11969
Location:773 → 827

SH3_PLCgamma2; Src homology 3 domain of Phospholipase C (PLC) gamma 2

cd13234
Location:840 → 910

PHsplit_PLC_gamma; Phospholipase C-gamma Split pleckstrin homology (PH) domain

cd13362
Location:22 → 140

PH_PLC_gamma; Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain

cl14615
Location:926 → 1031

PI-PLCc_GDPD_SF; Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases superfamily

cl17171
Location:475 → 510

PH-like; Pleckstrin homology-like domain