ARRB2
arrestin beta 2, the group of Classical arrestins
Basic information
Region (hg38): 17:4710596-4721499
Previous symbols: [ "ARR2" ]
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 ARRB2 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 | 1 | |||||
| missense | 15 | 16 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 1 | |||||
| Total | 0 | 0 | 15 | 1 | 2 |
Variants in ARRB2
This is a list of pathogenic ClinVar variants found in the ARRB2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 17-4715027-C-T | not specified | Uncertain significance (Dec 15, 2022) | ||
| 17-4715032-C-T | not specified | Uncertain significance (Jun 05, 2024) | ||
| 17-4716430-G-C | not specified | Uncertain significance (May 21, 2024) | ||
| 17-4716497-C-T | Benign (Feb 09, 2018) | |||
| 17-4716538-G-A | not specified | Uncertain significance (May 31, 2023) | ||
| 17-4716591-C-A | not specified | Uncertain significance (Apr 18, 2023) | ||
| 17-4717710-G-A | not specified | Uncertain significance (Jan 20, 2023) | ||
| 17-4717917-T-C | not specified | Uncertain significance (Dec 30, 2023) | ||
| 17-4717967-C-T | not specified | Uncertain significance (Jun 17, 2024) | ||
| 17-4717989-G-A | not specified | Uncertain significance (May 31, 2024) | ||
| 17-4718019-A-G | not specified | Uncertain significance (Jun 01, 2023) | ||
| 17-4718286-A-G | not specified | Likely benign (May 31, 2023) | ||
| 17-4718652-G-T | not specified | Uncertain significance (Jun 03, 2022) | ||
| 17-4719350-C-T | not specified | Uncertain significance (Dec 21, 2022) | ||
| 17-4719367-C-T | Benign (Feb 09, 2018) | |||
| 17-4719402-A-G | not specified | Uncertain significance (Mar 16, 2024) | ||
| 17-4720216-C-T | not specified | Likely benign (Jul 17, 2023) | ||
| 17-4720223-G-C | not specified | Uncertain significance (Apr 29, 2024) | ||
| 17-4720290-C-T | not specified | Uncertain significance (Sep 29, 2023) | ||
| 17-4720452-C-T | not specified | Uncertain significance (Feb 06, 2024) | ||
| 17-4720454-C-T | not specified | Uncertain significance (Jun 02, 2023) | ||
| 17-4720588-G-A | not specified | Uncertain significance (Dec 08, 2023) | ||
| 17-4720603-G-A | not specified | Uncertain significance (Mar 22, 2023) | ||
| 17-4720954-C-T | not specified | Uncertain significance (Sep 17, 2021) | ||
| 17-4721025-G-A | not specified | Uncertain significance (Sep 29, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ARRB2 | protein_coding | protein_coding | ENST00000412477 | 15 | 11011 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.507 | 0.493 | 125361 | 0 | 385 | 125746 | 0.00153 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.38 | 150 | 258 | 0.582 | 0.0000162 | 2769 |
| Missense in Polyphen | 93 | 171.24 | 0.54308 | 1853 | ||
| Synonymous | 0.881 | 98 | 110 | 0.893 | 0.00000700 | 855 |
| Loss of Function | 3.56 | 5 | 23.7 | 0.211 | 0.00000122 | 277 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00128 | 0.00125 |
| Ashkenazi Jewish | 0.00150 | 0.00149 |
| East Asian | 0.000896 | 0.000870 |
| Finnish | 0.00937 | 0.00858 |
| European (Non-Finnish) | 0.00112 | 0.00107 |
| Middle Eastern | 0.000896 | 0.000870 |
| South Asian | 0.000331 | 0.000327 |
| Other | 0.00134 | 0.00130 |
dbNSFP
Source:
- Function
- FUNCTION: Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta-arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G- protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the extent of beta-arrestin involvement appears to vary significantly depending on the receptor, agonist and cell type. Internalized arrestin-receptor complexes traffic to intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated internalization occur. Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta- arrestin at or near the plasma membrane and undergo rapid recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptors, for extended periods of time. Receptor resensitization then requires that receptor-bound arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. Mediates endocytosis of CCR7 following ligation of CCL19 but not CCL21. Involved in internalization of P2RY1, P2RY4, P2RY6 and P2RY11 and ATP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 and subsequent recycling or degradation. Involved in ubiquitination of IGF1R. Beta-arrestins function as multivalent adapter proteins that can switch the GPCR from a G-protein signaling mode that transmits short-lived signals from the plasma membrane via small molecule second messengers and ion channels to a beta-arrestin signaling mode that transmits a distinct set of signals that are initiated as the receptor internalizes and transits the intracellular compartment. Acts as signaling scaffold for MAPK pathways such as MAPK1/3 (ERK1/2) and MAPK10 (JNK3). ERK1/2 and JNK3 activated by the beta-arrestin scaffold are largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Acts as signaling scaffold for the AKT1 pathway. GPCRs for which the beta-arrestin-mediated signaling relies on both ARRB1 and ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the beta-arrestin- mediated signaling relies on either ARRB1 or ARRB2 and is inhibited by the other respective beta-arrestin form (reciprocal regulation). Increases ERK1/2 signaling in AGTR1- and AVPR2- mediated activation (reciprocal regulation). Involved in CCR7- mediated ERK1/2 signaling involving ligand CCL19. Is involved in type-1A angiotensin II receptor/AGTR1-mediated ERK activity. Is involved in type-1A angiotensin II receptor/AGTR1-mediated MAPK10 activity. Is involved in dopamine-stimulated AKT1 activity in the striatum by disrupting the association of AKT1 with its negative regulator PP2A. Involved in AGTR1-mediated chemotaxis. Appears to function as signaling scaffold involved in regulation of MIP-1- beta-stimulated CCR5-dependent chemotaxis. Involved in attenuation of NF-kappa-B-dependent transcription in response to GPCR or cytokine stimulation by interacting with and stabilizing CHUK. Suppresses UV-induced NF-kappa-B-dependent activation by interacting with CHUK. The function is promoted by stimulation of ADRB2 and dephosphorylation of ARRB2. Involved in p53/TP53- mediated apoptosis by regulating MDM2 and reducing the MDM2- mediated degradation of p53/TP53. May serve as nuclear messenger for GPCRs. Upon stimulation of OR1D2, may be involved in regulation of gene expression during the early processes of fertilization. Also involved in regulation of receptors other than GPCRs. Involved in endocytosis of TGFBR2 and TGFBR3 and down- regulates TGF-beta signaling such as NF-kappa-B activation. Involved in endocytosis of low-density lipoprotein receptor/LDLR. Involved in endocytosis of smoothened homolog/Smo, which also requires GRK2. Involved in endocytosis of SLC9A5. Involved in endocytosis of ENG and subsequent TGF-beta-mediated ERK activation and migration of epithelial cells. Involved in Toll-like receptor and IL-1 receptor signaling through the interaction with TRAF6 which prevents TRAF6 autoubiquitination and oligomerization required for activation of NF-kappa-B and JUN. Involved in insulin resistance by acting as insulin-induced signaling scaffold for SRC, AKT1 and INSR. Involved in regulation of inhibitory signaling of natural killer cells by recruiting PTPN6 and PTPN11 to KIR2DL1. Involved in IL8-mediated granule release in neutrophils. Involved in the internalization of the atypical chemokine receptor ACKR3. {ECO:0000269|PubMed:10644702, ECO:0000269|PubMed:11877451, ECO:0000269|PubMed:12488444, ECO:0000269|PubMed:12582207, ECO:0000269|PubMed:12949261, ECO:0000269|PubMed:12958365, ECO:0000269|PubMed:14711824, ECO:0000269|PubMed:15054093, ECO:0000269|PubMed:15125834, ECO:0000269|PubMed:15205453, ECO:0000269|PubMed:15475570, ECO:0000269|PubMed:15618519, ECO:0000269|PubMed:15635042, ECO:0000269|PubMed:15671180, ECO:0000269|PubMed:15699339, ECO:0000269|PubMed:15878855, ECO:0000269|PubMed:16144840, ECO:0000269|PubMed:16280323, ECO:0000269|PubMed:16378096, ECO:0000269|PubMed:16492667, ECO:0000269|PubMed:16820410, ECO:0000269|PubMed:17540773, ECO:0000269|PubMed:18419762, ECO:0000269|PubMed:18604210, ECO:0000269|PubMed:19325136, ECO:0000269|PubMed:19620252, ECO:0000269|PubMed:19643177, ECO:0000269|PubMed:20048153, ECO:0000269|PubMed:22457824}.;
- Pathway
- Relaxin signaling pathway - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Endocytosis - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Olfactory transduction - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Hedgehog signaling pathway - Homo sapiens (human);Diuretics Pathway, Pharmacodynamics;Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Corticotropin-releasing hormone signaling pathway;Human Complement System;Myometrial Relaxation and Contraction Pathways;Wnt Signaling Pathway;MAPK Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Chemokine signaling pathway;Hedgehog Signaling Pathway;Calcium Regulation in the Cardiac Cell;Signaling by GPCR;MAP2K and MAPK activation;Disease;Signaling by WNT;Signal Transduction;Vesicle-mediated transport;Membrane Trafficking;Hedgehog;Post-translational protein modification;Metabolism of proteins;Activation of SMO;Hedgehog;Ghrelin;G alpha (s) signalling events;Signaling by NOTCH1;Signaling by NOTCH;CRH;Thrombin signalling through proteinase activated receptors (PARs);Platelet activation, signaling and aggregation;Hedgehog ,on, state;Signaling by Hedgehog;Clathrin-mediated endocytosis;TGF_beta_Receptor;WNT5A-dependent internalization of FZD4;PCP/CE pathway;Beta-catenin independent WNT signaling;CXCR4-mediated signaling events;Hemostasis;Ub-specific processing proteases;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Thromboxane A2 receptor signaling;Noncanonical Wnt signaling pathway;Deubiquitination;Cargo recognition for clathrin-mediated endocytosis;Wnt;Signaling by RAS mutants;Signaling by high-kinase activity BRAF mutants;GPCR downstream signalling;Signaling by moderate kinase activity BRAF mutants;Paradoxical activation of RAF signaling by kinase inactive BRAF;ALK1 signaling events;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction;IL8- and CXCR1-mediated signaling events;Arf6 signaling events;Hedgehog signaling events mediated by Gli proteins;Signaling events mediated by the Hedgehog family;IL8- and CXCR2-mediated signaling events;Nephrin/Neph1 signaling in the kidney podocyte;TGF-beta receptor signaling;Atypical NF-kappaB pathway;Activated NOTCH1 Transmits Signal to the Nucleus
(Consensus)
Recessive Scores
- pRec
- 0.579
Intolerance Scores
- loftool
- 0.575
- rvis_EVS
- -0.67
- rvis_percentile_EVS
- 15.62
Haploinsufficiency Scores
- pHI
- 0.588
- hipred
- Y
- hipred_score
- 0.831
- ghis
- 0.632
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.785
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Arrb2
- 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); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; immune system 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); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- arrb2b
- Affected structure
- primordial germ cell
- Phenotype tag
- abnormal
- Phenotype quality
- mislocalised medially
Gene ontology
- Biological process
- negative regulation of protein phosphorylation;G protein-coupled receptor internalization;desensitization of G protein-coupled receptor signaling pathway by arrestin;positive regulation of receptor internalization;transcription by RNA polymerase II;transforming growth factor beta receptor signaling pathway;G protein-coupled receptor signaling pathway;dopamine receptor signaling pathway;brain development;adult walking behavior;positive regulation of gene expression;protein transport;protein ubiquitination;protein deubiquitination;platelet activation;negative regulation of protein ubiquitination;positive regulation of protein ubiquitination;receptor internalization;negative regulation of NF-kappaB transcription factor activity;positive regulation of synaptic transmission, dopaminergic;negative regulation of interleukin-1 beta production;negative regulation of interleukin-12 production;negative regulation of interleukin-6 production;negative regulation of tumor necrosis factor production;positive regulation of collagen biosynthetic process;positive regulation of peptidyl-serine phosphorylation;negative regulation of toll-like receptor signaling pathway;negative regulation of GTPase activity;negative regulation of smooth muscle cell apoptotic process;follicle-stimulating hormone signaling pathway;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;proteasome-mediated ubiquitin-dependent protein catabolic process;negative regulation of neuron apoptotic process;negative regulation of natural killer cell mediated cytotoxicity;positive regulation of peptidyl-tyrosine phosphorylation;detection of temperature stimulus involved in sensory perception of pain;positive regulation of protein kinase B signaling;negative regulation of protein kinase B signaling;positive regulation of calcium ion transport;Wnt signaling pathway, planar cell polarity pathway;excitatory postsynaptic potential;cell chemotaxis;regulation of androgen receptor signaling pathway;membrane organization;positive regulation of ERK1 and ERK2 cascade;negative regulation of release of cytochrome c from mitochondria;positive regulation of epithelial cell apoptotic process;positive regulation of DNA biosynthetic process;positive regulation of cardiac muscle cell differentiation
- Cellular component
- nucleus;cytoplasm;endosome;cytosol;plasma membrane;clathrin-coated pit;postsynaptic density;basolateral plasma membrane;endocytic vesicle;cytoplasmic vesicle;dendritic spine;intracellular membrane-bounded organelle;postsynaptic membrane
- Molecular function
- G protein-coupled receptor binding;signaling receptor binding;protein binding;enzyme binding;protein domain specific binding;ubiquitin protein ligase binding;alpha-1A adrenergic receptor binding;alpha-1B adrenergic receptor binding;angiotensin receptor binding;type 1 angiotensin receptor binding;D1 dopamine receptor binding;follicle-stimulating hormone receptor binding;type 2A serotonin receptor binding;platelet activating factor receptor binding;protein-containing complex scaffold activity;identical protein binding;protein kinase B binding;protein-containing complex binding;mitogen-activated protein kinase binding;14-3-3 protein binding;arrestin family protein binding