Seroatlas · Human Serome Atlas

PLCG2

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2

Also known as: PLCG2_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: P16885
Gene: PLCG2
Ensembl: ENSG00000197943
Chromosome: 16
Canonical length: 1265 aa
Protein class: Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins, RAS pathway related proteins
Subcellular location: Nucleoplasm,Vesicles,Cytosol

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1265 residues, UniProt reviewed canonical sequence.

>P16885|PLCG2
     1  MSTTVNVDSL AEYEKSQIKR ALELGTVMTV FSFRKSTPER RTVQVIMETR QVAWSKTADK
    61  IEGFLDIMEI KEIRPGKNSK DFERAKAVRQ KEDCCFTILY GTQFVLSTLS LAADSKEDAV
   121  NWLSGLKILH QEAMNASTPT IIESWLRKQI YSVDQTRRNS ISLRELKTIL PLINFKVSSA
   181  KFLKDKFVEI GAHKDELSFE QFHLFYKKLM FEQQKSILDE FKKDSSVFIL GNTDRPDASA
   241  VYLHDFQRFL IHEQQEHWAQ DLNKVRERMT KFIDDTMRET AEPFLFVDEF LTYLFSRENS
   301  IWDEKYDAVD MQDMNNPLSH YWISSSHNTY LTGDQLRSES SPEAYIRCLR MGCRCIELDC
   361  WDGPDGKPVI YHGWTRTTKI KFDDVVQAIK DHAFVTSSFP VILSIEEHCS VEQQRHMAKA
   421  FKEVFGDLLL TKPTEASADQ LPSPSQLREK IIIKHKKLGP RGDVDVNMED KKDEHKQQGE
   481  LYMWDSIDQK WTRHYCAIAD AKLSFSDDIE QTMEEEVPQD IPPTELHFGE KWFHKKVEKR
   541  TSAEKLLQEY CMETGGKDGT FLVRESETFP NDYTLSFWRS GRVQHCRIRS TMEGGTLKYY
   601  LTDNLTFSSI YALIQHYRET HLRCAEFELR LTDPVPNPNP HESKPWYYDS LSRGEAEDML
   661  MRIPRDGAFL IRKREGSDSY AITFRARGKV KHCRINRDGR HFVLGTSAYF ESLVELVSYY
   721  EKHSLYRKMR LRYPVTPELL ERYNMERDIN SLYDVSRMYV DPSEINPSMP QRTVKALYDY
   781  KAKRSDELSF CRGALIHNVS KEPGGWWKGD YGTRIQQYFP SNYVEDISTA DFEELEKQII
   841  EDNPLGSLCR GILDLNTYNV VKAPQGKNQK SFVFILEPKQ QGDPPVEFAT DRVEELFEWF
   901  QSIREITWKI DTKENNMKYW EKNQSIAIEL SDLVVYCKPT SKTKDNLENP DFREIRSFVE
   961  TKADSIIRQK PVDLLKYNQK GLTRVYPKGQ RVDSSNYDPF RLWLCGSQMV ALNFQTADKY
  1021  MQMNHALFSL NGRTGYVLQP ESMRTEKYDP MPPESQRKIL MTLTVKVLGA RHLPKLGRSI
  1081  ACPFVEVEIC GAEYDNNKFK TTVVNDNGLS PIWAPTQEKV TFEIYDPNLA FLRFVVYEED
  1141  MFSDPNFLAH ATYPIKAVKS GFRSVPLKNG YSEDIELASL LVFCEMRPVL ESEEELYSSC
  1201  RQLRRRQEEL NNQLFLYDTH QNLRNANRDA LVKEFSVNEN QLQLYQEKCN KRLREKRVSN
  1261  SKFYS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PLCG2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.27
Highest tissue expression: 42 nTPM

Expression across tissuesHPA

Tissue

tonsil: 42 nTPM
lymph node: 42 nTPM
spleen: 24 nTPM
appendix: 20 nTPM
bone marrow: 18 nTPM
epididymis: 18 nTPM

Single-cell type

renal collecting duct intercalated cells: 1,099 nCPM
podocytes: 539 nCPM
microglia: 346 nCPM
distal convoluted tubule cells: 218 nCPM
renal connecting tubule cells: 195 nCPM
renal collecting duct principal cells: 150 nCPM

Immune cell

NK-cell: 37 nTPM
memory B-cell: 30 nTPM
neutrophil: 23 nTPM
non-classical monocyte: 23 nTPM
naive B-cell: 22 nTPM
eosinophil: 21 nTPM

Brain region

cerebellum: 2,744 nTPM
white matter: 2,188 nTPM
cerebral cortex: 2,138 nTPM
choroid plexus: 2,040 nTPM
medulla oblongata: 1,932 nTPM
thalamus: 1,896 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PLCG2.

Disease | AllUniProt

Conditions PLCG2 is implicated in, by any mechanism.

Familial cold autoinflammatory syndrome 3 (FCAS3) MIM:614468
Autoinflammation, antibody deficiency, and immune dysregulation (APLAID) MIM:614878

Disease | GeneticClinVar

10 pathogenic / likely-pathogenic of 1,835 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Familial cold autoinflammatory syndrome 3
Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation

Disease | ImmuneIEDB

Conditions an epitope on PLCG2 was assayed in.

narcolepsy B cell
multiple sclerosis B cell
peripheral nervous system disease B cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.28
gnomAD pLI: 1
gnomAD missense Z: 0.82
DepMap mean gene effect: 0.01
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of PLCG2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads PLCG2 as an antibody target. Whether an autoantibody or antibody against PLCG2 could matter depends on whether native PLCG2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

PLCG2 is annotated at the cell surface, where native PLCG2 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Source-annotated serology context

The source annotations explicitly mention antibody, autoantibody, autoantigen, or autoimmune context. This is biological context, not study-specific reactivity.

Mutations in this gene have been found in autoinflammation, antibody deficiency, and immune dysregulation syndrome and familial cold autoinflammatory syndrome 3.

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