F2RL1
F2R like trypsin receptor 1, the group of F2R receptors
Basic information
Region (hg38): 5:76818932-76835315
Previous symbols: [ "GPR11" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the F2RL1 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 | 2 | |||||
| missense | 19 | 19 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 19 | 1 | 1 |
Variants in F2RL1
This is a list of pathogenic ClinVar variants found in the F2RL1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-76819186-C-A | Benign (Jul 19, 2018) | |||
| 5-76819187-G-A | not specified | Uncertain significance (Jan 06, 2023) | ||
| 5-76819196-G-C | not specified | Uncertain significance (Sep 30, 2021) | ||
| 5-76819234-G-T | not specified | Uncertain significance (Mar 06, 2023) | ||
| 5-76832695-A-G | not specified | Uncertain significance (Jul 17, 2023) | ||
| 5-76832774-A-G | not specified | Uncertain significance (Oct 26, 2022) | ||
| 5-76832867-T-C | not specified | Uncertain significance (Jun 17, 2022) | ||
| 5-76832887-G-A | not specified | Uncertain significance (Nov 19, 2022) | ||
| 5-76832899-T-G | not specified | Uncertain significance (Sep 14, 2022) | ||
| 5-76832984-T-C | not specified | Uncertain significance (Jan 20, 2023) | ||
| 5-76833169-G-A | not specified | Uncertain significance (Jun 18, 2021) | ||
| 5-76833172-A-G | not specified | Uncertain significance (May 10, 2022) | ||
| 5-76833199-A-G | not specified | Uncertain significance (Jul 06, 2022) | ||
| 5-76833299-C-T | not specified | Uncertain significance (Dec 14, 2023) | ||
| 5-76833313-G-A | not specified | Uncertain significance (Nov 18, 2023) | ||
| 5-76833313-G-C | not specified | Uncertain significance (Mar 14, 2023) | ||
| 5-76833321-C-G | not specified | Uncertain significance (Dec 27, 2023) | ||
| 5-76833350-T-C | not specified | Uncertain significance (May 06, 2022) | ||
| 5-76833424-G-A | not specified | Uncertain significance (May 14, 2024) | ||
| 5-76833458-G-A | not specified | Uncertain significance (May 07, 2024) | ||
| 5-76833521-T-A | not specified | Uncertain significance (Mar 01, 2023) | ||
| 5-76833685-C-T | not specified | Uncertain significance (Apr 24, 2023) | ||
| 5-76833696-T-C | Likely benign (Jul 22, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| F2RL1 | protein_coding | protein_coding | ENST00000296677 | 2 | 16383 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000148 | 0.677 | 125651 | 0 | 95 | 125746 | 0.000378 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.495 | 184 | 204 | 0.903 | 0.00000996 | 2575 |
| Missense in Polyphen | 51 | 59.349 | 0.85932 | 780 | ||
| Synonymous | 0.144 | 81 | 82.7 | 0.980 | 0.00000426 | 843 |
| Loss of Function | 0.851 | 7 | 9.89 | 0.708 | 6.94e-7 | 114 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000148 | 0.000148 |
| Ashkenazi Jewish | 0.0000992 | 0.0000992 |
| East Asian | 0.000272 | 0.000272 |
| Finnish | 0.000785 | 0.000786 |
| European (Non-Finnish) | 0.000546 | 0.000545 |
| Middle Eastern | 0.000272 | 0.000272 |
| South Asian | 0.000131 | 0.000131 |
| Other | 0.000326 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Receptor for trypsin and trypsin-like enzymes coupled to G proteins (PubMed:28445455). Its function is mediated through the activation of several signaling pathways including phospholipase C (PLC), intracellular calcium, mitogen-activated protein kinase (MAPK), I-kappaB kinase/NF-kappaB and Rho (PubMed:28445455). Can also be transactivated by cleaved F2R/PAR1. Involved in modulation of inflammatory responses and regulation of innate and adaptive immunity, and acts as a sensor for proteolytic enzymes generated during infection. Generally is promoting inflammation. Can signal synergistically with TLR4 and probably TLR2 in inflammatory responses and modulates TLR3 signaling. Has a protective role in establishing the endothelial barrier; the activity involves coagulation factor X. Regulates endothelial cell barrier integrity during neutrophil extravasation, probably following proteolytic cleavage by PRTN3 (PubMed:23202369). Proposed to have a bronchoprotective role in airway epithelium, but also shown to compromise the airway epithelial barrier by interrupting E- cadherin adhesion (PubMed:10086357). Involved in the regulation of vascular tone; activation results in hypotension presumably mediated by vasodilation. Associates with a subset of G proteins alpha subunits such as GNAQ, GNA11, GNA14, GNA12 and GNA13, but probably not with G(o) alpha, G(i) subunit alpha-1 and G(i) subunit alpha-2. However, according to PubMed:21627585 can signal through G(i) subunit alpha. Believed to be a class B receptor which internalizes as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptor, for extended periods of time. Mediates inhibition of TNF-alpha stimulated JNK phosphorylation via coupling to GNAQ and GNA11; the function involves dissociation of RIPK1 and TRADD from TNFR1. Mediates phosphorylation of nuclear factor NF-kappa-B RELA subunit at 'Ser-536'; the function involves IKBKB and is predominantly independent of G proteins. Involved in cellular migration. Involved in cytoskeletal rearrangement and chemotaxis through beta-arrestin-promoted scaffolds; the function is independent of GNAQ and GNA11 and involves promotion of cofilin dephosphorylation and actin filament severing. Induces redistribution of COPS5 from the plasma membrane to the cytosol and activation of the JNK cascade is mediated by COPS5. Involved in the recruitment of leukocytes to the sites of inflammation and is the major PAR receptor capable of modulating eosinophil function such as proinflammatory cytokine secretion, superoxide production and degranulation. During inflammation promotes dendritic cell maturation, trafficking to the lymph nodes and subsequent T-cell activation. Involved in antimicrobial response of innate immnune cells; activation enhances phagocytosis of Gram-positive and killing of Gram-negative bacteria. Acts synergistically with interferon-gamma in enhancing antiviral responses. Implicated in a number of acute and chronic inflammatory diseases such as of the joints, lungs, brain, gastrointestinal tract, periodontium, skin, and vascular systems, and in autoimmune disorders. {ECO:0000269|PubMed:10086357, ECO:0000269|PubMed:10725339, ECO:0000269|PubMed:11413129, ECO:0000269|PubMed:11441110, ECO:0000269|PubMed:11447194, ECO:0000269|PubMed:11714832, ECO:0000269|PubMed:12832443, ECO:0000269|PubMed:15155775, ECO:0000269|PubMed:16359518, ECO:0000269|PubMed:16410250, ECO:0000269|PubMed:16478888, ECO:0000269|PubMed:16714334, ECO:0000269|PubMed:17404307, ECO:0000269|PubMed:17500066, ECO:0000269|PubMed:18424071, ECO:0000269|PubMed:18453611, ECO:0000269|PubMed:18474671, ECO:0000269|PubMed:18622013, ECO:0000269|PubMed:19494303, ECO:0000269|PubMed:19781631, ECO:0000269|PubMed:19864598, ECO:0000269|PubMed:19865078, ECO:0000269|PubMed:20826780, ECO:0000269|PubMed:21501162, ECO:0000269|PubMed:23202369, ECO:0000269|PubMed:28445455}.;
- Pathway
- Inflammatory mediator regulation of TRP channels - Homo sapiens (human);African trypanosomiasis - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);GPCRs, Class A Rhodopsin-like;Signaling by GPCR;Signal Transduction;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G alpha (q) signalling events;GPCR downstream signalling
(Consensus)
Recessive Scores
- pRec
- 0.173
Intolerance Scores
- loftool
- 0.732
- rvis_EVS
- -0.38
- rvis_percentile_EVS
- 27.69
Haploinsufficiency Scores
- pHI
- 0.352
- hipred
- Y
- hipred_score
- 0.540
- ghis
- 0.494
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.318
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- F2rl1
- Phenotype
- renal/urinary system phenotype; skeleton phenotype; immune system 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); limbs/digits/tail phenotype; neoplasm; hematopoietic system 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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; embryo phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland 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);
Gene ontology
- Biological process
- T cell activation involved in immune response;positive regulation of leukocyte chemotaxis;positive regulation of cytokine secretion involved in immune response;positive regulation of glomerular filtration;inflammatory response;G protein-coupled receptor signaling pathway;positive regulation of cytosolic calcium ion concentration;blood coagulation;negative regulation of tumor necrosis factor-mediated signaling pathway;positive regulation of phosphatidylinositol 3-kinase signaling;regulation of blood coagulation;positive regulation of cell migration;positive regulation of actin filament depolymerization;positive regulation of pseudopodium assembly;positive regulation of superoxide anion generation;positive regulation of toll-like receptor 2 signaling pathway;negative regulation of toll-like receptor 3 signaling pathway;positive regulation of toll-like receptor 3 signaling pathway;positive regulation of toll-like receptor 4 signaling pathway;positive regulation of Rho protein signal transduction;chemokine (C-C motif) ligand 2 secretion;neutrophil activation;regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of eosinophil degranulation;positive regulation of GTPase activity;innate immune response;cell-cell junction maintenance;positive regulation of transcription by RNA polymerase II;regulation of JNK cascade;negative regulation of JNK cascade;positive regulation of JNK cascade;interleukin-1 beta secretion;leukocyte migration;positive regulation of chemotaxis;positive regulation of positive chemotaxis;positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway;defense response to virus;positive regulation of phagocytosis, engulfment;establishment of endothelial barrier;positive regulation of ERK1 and ERK2 cascade;thrombin-activated receptor signaling pathway;leukocyte proliferation;positive regulation of neutrophil mediated killing of gram-negative bacterium;interleukin-10 secretion;interferon-gamma secretion;chemokine secretion;negative regulation of chemokine secretion;mature conventional dendritic cell differentiation;positive regulation of blood vessel diameter;positive regulation of renin secretion into blood stream;positive regulation of interleukin-8 secretion;positive regulation of interleukin-6 secretion
- Cellular component
- early endosome;Golgi apparatus;plasma membrane;integral component of plasma membrane;pseudopodium
- Molecular function
- G-protein alpha-subunit binding;G protein-coupled receptor activity;signaling receptor binding;protein binding;thrombin-activated receptor activity;G-protein beta-subunit binding;signaling receptor activity