PLCG1
phospholipase C gamma 1, the group of Phospholipases|Pleckstrin homology domain containing|MicroRNA protein coding host genes|SH2 domain containing|C2 domain containing phospholipases|EF-hand domain containing
Basic information
Region (hg38): 20:41136959-41196801
Previous symbols: [ "PLC1" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Immune dysregulation, autoimmunity, and autoinflammation | AD | Allergy/Immunology/Infectious; Hematologic | The condition has been described as involving immune dysfucntion and hematologic abnormalities, and medical management (eg, with immunosuppressive agents and tranfusions) has been reported as beneficial | Allergy/Immunology/Infectious; Hematologic | 37422272 |
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (26 variants)
- not provided (5 variants)
- Hereditary breast ovarian cancer syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLCG1 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 | 5 | |||||
| missense | 26 | 27 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 26 | 4 | 2 |
Variants in PLCG1
This is a list of pathogenic ClinVar variants found in the PLCG1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 20-41137714-C-T | not specified | Uncertain significance (Feb 14, 2024) | ||
| 20-41137831-C-T | not specified | Uncertain significance (Dec 15, 2023) | ||
| 20-41159615-G-T | not specified | Uncertain significance (Apr 13, 2023) | ||
| 20-41159720-A-G | not specified | Uncertain significance (Oct 24, 2023) | ||
| 20-41159935-C-G | not specified | Uncertain significance (Oct 31, 2023) | ||
| 20-41160141-A-G | not specified | Uncertain significance (Apr 19, 2023) | ||
| 20-41162528-C-T | not specified | Uncertain significance (Jan 24, 2024) | ||
| 20-41162979-G-A | not specified | Uncertain significance (May 11, 2022) | ||
| 20-41163248-C-A | not specified | Uncertain significance (Apr 03, 2023) | ||
| 20-41163248-C-G | not specified | Uncertain significance (Jun 02, 2023) | ||
| 20-41163252-C-A | not specified | Uncertain significance (Jan 29, 2024) | ||
| 20-41163791-A-G | not specified | Uncertain significance (Sep 23, 2023) | ||
| 20-41164170-A-G | not specified | Uncertain significance (May 11, 2022) | ||
| 20-41165009-G-C | not specified | Uncertain significance (Jan 31, 2024) | ||
| 20-41165088-A-G | not specified | Uncertain significance (Apr 26, 2023) | ||
| 20-41165514-G-T | not specified | Uncertain significance (May 18, 2022) | ||
| 20-41165547-A-G | not specified | Uncertain significance (Nov 12, 2021) | ||
| 20-41165667-A-G | not specified | Likely benign (Aug 08, 2022) | ||
| 20-41165700-G-A | PLCG1-related disorder | Uncertain significance (Dec 21, 2023) | ||
| 20-41166201-G-A | not specified | Uncertain significance (Mar 31, 2023) | ||
| 20-41166219-C-T | not specified | Uncertain significance (Aug 09, 2021) | ||
| 20-41166245-G-A | Benign (Aug 10, 2018) | |||
| 20-41166297-C-G | PLCG1-related disorder | Uncertain significance (Feb 29, 2024) | ||
| 20-41166307-A-G | not specified | Uncertain significance (Feb 26, 2024) | ||
| 20-41166496-C-G | not specified | Uncertain significance (Jul 20, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PLCG1 | protein_coding | protein_coding | ENST00000373272 | 32 | 46030 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0000793 | 1.00 | 125709 | 0 | 39 | 125748 | 0.000155 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.24 | 520 | 773 | 0.672 | 0.0000498 | 8500 |
| Missense in Polyphen | 161 | 326.19 | 0.49357 | 3524 | ||
| Synonymous | -0.0462 | 300 | 299 | 1.00 | 0.0000190 | 2433 |
| Loss of Function | 5.94 | 24 | 82.1 | 0.292 | 0.00000474 | 850 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000514 | 0.000514 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000113 | 0.000109 |
| Finnish | 0.000185 | 0.000185 |
| European (Non-Finnish) | 0.000169 | 0.000167 |
| Middle Eastern | 0.000113 | 0.000109 |
| South Asian | 0.0000980 | 0.0000980 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand- mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, FGFR1, FGFR2, FGFR3 and FGFR4. Plays a role in actin reorganization and cell migration. {ECO:0000269|PubMed:17229814}.;
- Pathway
- Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Non-small cell lung cancer - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Inositol phosphate metabolism - Homo sapiens (human);VEGF signaling pathway - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);Axon guidance - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Glioma - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Vibrio cholerae infection - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;Leukocyte transendothelial migration - Homo sapiens (human);Proton Pump Inhibitor Pathway, Pharmacodynamics;VEGF Signaling Pathway;Fc Epsilon Receptor I Signaling in Mast Cells;Angiogenesis;IL-1 signaling pathway;Angiogenesis overview;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Leptin signaling pathway;Signaling Pathways in Glioblastoma;B Cell Receptor Signaling Pathway;Corticotropin-releasing hormone signaling pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;PDGF Pathway;Primary Focal Segmental Glomerulosclerosis FSGS;T-Cell Receptor and Co-stimulatory Signaling;nerve growth factor pathway (ngf);Myometrial Relaxation and Contraction Pathways;Kit receptor signaling pathway;MFAP5-mediated ovarian cancer cell motility and invasiveness;BDNF-TrkB Signaling;Association Between Physico-Chemical Features and Toxicity Associated Pathways;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;GPR40 Pathway;VEGFA-VEGFR2 Signaling Pathway;PDGFR-beta pathway;MET in type 1 papillary renal cell carcinoma;Ras Signaling;EGF-EGFR Signaling Pathway;ErbB Signaling Pathway;T-Cell antigen Receptor (TCR) Signaling Pathway;Developmental Biology;Signaling by FGFR2;Phospholipase C-mediated cascade; FGFR2;D-<i>myo</i>-inositol (1,4,5)-trisphosphate biosynthesis;Downstream signaling of activated FGFR2;Antigen activates B Cell Receptor (BCR) leading to generation of second messengers;Downstream signaling of activated FGFR3;Disease;Signaling by FGFR3;Signal Transduction;Downstream signaling of activated FGFR4;DAP12 signaling;DAP12 interactions;Signaling by FGFR4;Signaling by FGFR;ionomycin and phorbal ester signaling pathway;pertussis toxin-insensitive ccr5 signaling in macrophage;bioactive peptide induced signaling pathway;role of erk5 in neuronal survival pathway;erk and pi-3 kinase are necessary for collagen binding in corneal epithelia;links between pyk2 and map kinases;role of egf receptor transactivation by gpcrs in cardiac hypertrophy;egf signaling pathway;angiotensin ii mediated activation of jnk pathway via pyk2 dependent signaling;phospholipase c signaling pathway;cxcr4 signaling pathway;role of mef2d in t-cell apoptosis;vegf hypoxia and angiogenesis;VEGFA-VEGFR2 Pathway;effects of calcineurin in keratinocyte differentiation;signaling pathway from g-protein families;phosphoinositides and their downstream targets;trka receptor signaling pathway;t cell receptor signaling pathway;bcr signaling pathway;Cytokine Signaling in Immune system;Generation of second messenger molecules;TCR signaling;Signaling by the B Cell Receptor (BCR);Signaling by PDGF;CD4 T cell receptor signaling-ERK cascade;Inositol phosphate metabolism;Role of phospholipids in phagocytosis;Fcgamma receptor (FCGR) dependent phagocytosis;HGF;FCERI mediated MAPK activation;FCERI mediated Ca+2 mobilization;Fc epsilon receptor (FCERI) signaling;TCR;Innate Immune System;Immune System;Metabolism;FGF;phospholipases;Signaling by FGFR2 in disease;Adaptive Immune System;D-<i>myo</i>-inositol-5-phosphate metabolism;superpathway of inositol phosphate compounds;KitReceptor;Fibroblast growth factor-1;BCR;EGFR interacts with phospholipase C-gamma;CRH;actions of nitric oxide in the heart;pdgf signaling pathway;Signaling by EGFR;epo signaling pathway;Frs2-mediated activation;tpo signaling pathway;Prolonged ERK activation events;Signalling to ERKs;PLC-gamma1 signalling;Signaling by NTRK1 (TRKA);Role of second messengers in netrin-1 signaling;fc epsilon receptor i signaling in mast cells;Activated NTRK2 signals through PLCG1;Signaling by NTRK2 (TRKB);Signaling by NTRKs;BDNF;EGFR1;Synthesis of IP3 and IP4 in the cytosol;growth hormone signaling pathway;PECAM1 interactions;Cell surface interactions at the vascular wall;Hemostasis;DAG and IP3 signaling;Inositol phosphate metabolism;PDGF;E-cadherin signaling in keratinocytes;NGF;Netrin-1 signaling;Downstream signal transduction;Class I PI3K signaling events;Signaling by EGFRvIII in Cancer;Signaling by EGFR in Cancer;Signaling by VEGF;EPO signaling pathway;Signaling by FGFR3 point mutants in cancer;Signaling by FGFR4 in disease;RET signaling;Axon guidance;Signaling by FGFR3 in disease;Signaling by FGFR in disease;Leptin;PLCG1 events in ERBB2 signaling;Signaling by ERBB2;IL6;Signaling by FGFR1 in disease;Constitutive Signaling by EGFRvIII;Signaling by Receptor Tyrosine Kinases;VEGF;Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants;Signaling by Ligand-Responsive EGFR Variants in Cancer;Intracellular signaling by second messengers;Regulation of CDC42 activity;Phospholipase C-mediated cascade: FGFR1;Neurotrophic factor-mediated Trk receptor signaling;LPA receptor mediated events;Diseases of signal transduction;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Fc-epsilon receptor I signaling in mast cells;Netrin-mediated signaling events;N-cadherin signaling events;ISG15 antiviral mechanism;Antiviral mechanism by IFN-stimulated genes;Interferon Signaling;S1P1 pathway;Signaling events mediated by focal adhesion kinase;TCR signaling in naïve CD8+ T cells;S1P4 pathway;Nongenotropic Androgen signaling;Trk receptor signaling mediated by PI3K and PLC-gamma;PDGFR-beta signaling pathway;Downstream signaling of activated FGFR1;FGF signaling pathway;Signaling events mediated by VEGFR1 and VEGFR2;TCR signaling in naïve CD4+ T cells;Nephrin/Neph1 signaling in the kidney podocyte;PDGFR-alpha signaling pathway;EPHA forward signaling;VEGFR1 specific signals;CD4 T cell receptor signaling-JNK cascade;CD4 T cell receptor signaling-NFkB cascade;VEGFR2 mediated cell proliferation;Signaling by FGFR1;CD4 T cell receptor signaling;Phospholipase C-mediated cascade; FGFR3;Phospholipase C-mediated cascade; FGFR4
(Consensus)
Recessive Scores
- pRec
- 0.633
Intolerance Scores
- loftool
- 0.597
- rvis_EVS
- -1.97
- rvis_percentile_EVS
- 1.82
Haploinsufficiency Scores
- pHI
- 0.709
- hipred
- Y
- hipred_score
- 0.706
- ghis
- 0.591
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.763
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Plcg1
- Phenotype
- growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; cellular phenotype; embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; 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); digestive/alimentary phenotype; hearing/vestibular/ear phenotype; immune system phenotype;
Zebrafish Information Network
- Gene name
- plcg1
- Affected structure
- nucleate erythrocyte
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- in utero embryonic development;signal transduction;epidermal growth factor receptor signaling pathway;activation of phospholipase C activity;axon guidance;phospholipid catabolic process;positive regulation of epithelial cell migration;positive regulation of phospholipase C activity;viral process;cell migration;calcium-mediated signaling;inositol trisphosphate biosynthetic process;Fc-epsilon receptor signaling pathway;Fc-gamma receptor signaling pathway involved in phagocytosis;positive regulation of blood vessel endothelial cell migration;inositol phosphate metabolic process;positive regulation of angiogenesis;phosphatidylinositol-mediated signaling;modulation of chemical synaptic transmission;T cell receptor signaling pathway;leukocyte migration;release of sequestered calcium ion into cytosol;positive regulation of release of sequestered calcium ion into cytosol;cellular response to epidermal growth factor stimulus;positive regulation of vascular endothelial cell proliferation;positive regulation of endothelial cell apoptotic process
- Cellular component
- ruffle;cytoplasm;cytosol;plasma membrane;cell-cell junction;COP9 signalosome;lamellipodium;cell projection;Schaffer collateral - CA1 synapse;glutamatergic synapse
- Molecular function
- phosphatidylinositol phospholipase C activity;phospholipase C activity;neurotrophin TRKA receptor binding;calcium ion binding;protein binding;protein kinase binding;receptor tyrosine kinase binding;glutamate receptor binding