ARRB1
arrestin beta 1, the group of Classical arrestins|MicroRNA protein coding host genes
Basic information
Region (hg38): 11:75260121-75351705
Previous symbols: [ "ARR1" ]
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 ARRB1 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 | 0 | |||||
| missense | 17 | 17 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 17 | 0 | 0 |
Variants in ARRB1
This is a list of pathogenic ClinVar variants found in the ARRB1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 11-75266168-T-C | not specified | Uncertain significance (Mar 17, 2023) | ||
| 11-75267689-T-A | not specified | Uncertain significance (Jun 14, 2023) | ||
| 11-75268904-G-C | not specified | Uncertain significance (Sep 23, 2023) | ||
| 11-75268955-C-T | not specified | Uncertain significance (Jan 06, 2023) | ||
| 11-75272959-G-A | not specified | Uncertain significance (Dec 21, 2022) | ||
| 11-75272961-T-C | not specified | Uncertain significance (Jun 01, 2023) | ||
| 11-75276893-A-G | not specified | Uncertain significance (Jun 10, 2022) | ||
| 11-75277415-C-T | not specified | Uncertain significance (May 23, 2023) | ||
| 11-75278696-C-A | not specified | Uncertain significance (Dec 28, 2023) | ||
| 11-75281096-A-G | not specified | Uncertain significance (Dec 18, 2023) | ||
| 11-75281984-G-A | not specified | Uncertain significance (Oct 10, 2023) | ||
| 11-75281990-A-C | not specified | Uncertain significance (Jul 12, 2022) | ||
| 11-75283346-G-A | not specified | Uncertain significance (Feb 11, 2022) | ||
| 11-75283348-G-T | not specified | Uncertain significance (Apr 15, 2024) | ||
| 11-75283355-G-C | not specified | Uncertain significance (Dec 26, 2023) | ||
| 11-75283378-G-A | not specified | Uncertain significance (Oct 12, 2022) | ||
| 11-75283397-C-A | not specified | Uncertain significance (Sep 16, 2021) | ||
| 11-75283397-C-T | not specified | Uncertain significance (May 04, 2022) | ||
| 11-75284271-C-A | not specified | Uncertain significance (May 10, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ARRB1 | protein_coding | protein_coding | ENST00000420843 | 16 | 87648 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.994 | 0.00606 | 125740 | 0 | 5 | 125745 | 0.0000199 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.36 | 157 | 265 | 0.593 | 0.0000170 | 2716 |
| Missense in Polyphen | 44 | 97.313 | 0.45215 | 967 | ||
| Synonymous | 0.833 | 99 | 110 | 0.899 | 0.00000774 | 805 |
| Loss of Function | 4.16 | 2 | 24.0 | 0.0833 | 0.00000111 | 299 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000566 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000266 | 0.0000264 |
| Middle Eastern | 0.0000566 | 0.0000544 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
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. Involved in internalization of P2RY4 and UTP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 ands subsequent recycling. Involved in the degradation of cAMP by recruiting cAMP phosphodiesterases to ligand-activated receptors. 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). ERK1/2 activated by the beta- arrestin scaffold is largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Recruits c-Src/SRC to ADRB2 resulting in ERK activation. 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). Inhibits ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Is required for SP-stimulated endocytosis of NK1R and recruits c-Src/SRC to internalized NK1R resulting in ERK1/2 activation, which is required for the antiapoptotic effects of SP. Is involved in proteinase-activated F2RL1-mediated ERK activity. Acts as signaling scaffold for the AKT1 pathway. Is involved in alpha- thrombin-stimulated AKT1 signaling. Is involved in IGF1-stimulated AKT1 signaling leading to increased protection from apoptosis. Involved in activation of the p38 MAPK signaling pathway and in actin bundle formation. Involved in F2RL1-mediated cytoskeletal rearrangement and chemotaxis. Involved in AGTR1-mediated stress fiber formation by acting together with GNAQ to activate RHOA. 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. May serve as nuclear messenger for GPCRs. Involved in OPRD1- stimulated transcriptional regulation by translocating to CDKN1B and FOS promoter regions and recruiting EP300 resulting in acetylation of histone H4. Involved in regulation of LEF1 transcriptional activity via interaction with DVL1 and/or DVL2 Also involved in regulation of receptors other than GPCRs. 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. Binds phosphoinositides. Binds inositolhexakisphosphate (InsP6) (By similarity). Involved in IL8-mediated granule release in neutrophils. Required for atypical chemokine receptor ACKR2- induced RAC1-LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. Involved in the internalization of the atypical chemokine receptor ACKR3. Negatively regulates the NOTCH signaling pathway by mediating the ubiquitination and degradation of NOTCH1 by ITCH. Participates to the recruitment of the ubiquitin-protein ligase to the receptor (PubMed:23886940). {ECO:0000250, ECO:0000269|PubMed:12464600, ECO:0000269|PubMed:14711824, ECO:0000269|PubMed:15475570, ECO:0000269|PubMed:15611106, ECO:0000269|PubMed:15671180, ECO:0000269|PubMed:15878855, ECO:0000269|PubMed:16144840, ECO:0000269|PubMed:16280323, ECO:0000269|PubMed:16378096, ECO:0000269|PubMed:16492667, ECO:0000269|PubMed:16709866, ECO:0000269|PubMed:18337459, ECO:0000269|PubMed:18419762, ECO:0000269|PubMed:19620252, ECO:0000269|PubMed:19643177, ECO:0000269|PubMed:22457824, ECO:0000269|PubMed:23341447, ECO:0000269|PubMed:23633677, ECO:0000269|PubMed:23886940}.;
- Pathway
- Relaxin signaling pathway - 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);Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;IGF-Ncore;WNT-Ncore;HH-Ncore;EGF-Ncore;NOTCH-Ncore;Corticotropin-releasing hormone signaling pathway;Myometrial Relaxation and Contraction Pathways;MAPK Signaling Pathway;Chemokine signaling pathway;Hedgehog Signaling Pathway;Calcium Regulation in the Cardiac Cell;Golgi Associated Vesicle Biogenesis;Signaling by GPCR;MAP2K and MAPK activation;Lysosome Vesicle Biogenesis;Clathrin derived vesicle budding;Disease;trans-Golgi Network Vesicle Budding;Signal Transduction;Vesicle-mediated transport;visual signal transduction;attenuation of gpcr signaling;role of -arrestins in the activation and targeting of map kinases;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Activation of SMO;Ghrelin;G alpha (s) signalling events;Signaling by NOTCH1;Signaling by NOTCH;roles of arrestin dependent recruitment of src kinases in gpcr signaling;CRH;Thrombin signalling through proteinase activated receptors (PARs);Platelet activation, signaling and aggregation;Hedgehog ,on, state;Signaling by Hedgehog;Clathrin-mediated endocytosis;Hemostasis;-arrestins in gpcr desensitization;Ub-specific processing proteases;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Deubiquitination;Cargo recognition for clathrin-mediated endocytosis;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;PAR1-mediated thrombin signaling events;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction;IL8- and CXCR1-mediated signaling events;CXCR3-mediated signaling events;Arf6 signaling events;IL8- and CXCR2-mediated signaling events;Activated NOTCH1 Transmits Signal to the Nucleus
(Consensus)
Recessive Scores
- pRec
- 0.175
Intolerance Scores
- loftool
- 0.405
- rvis_EVS
- -0.84
- rvis_percentile_EVS
- 11.18
Haploinsufficiency Scores
- pHI
- 0.267
- hipred
- Y
- hipred_score
- 0.728
- ghis
- 0.495
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.981
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Arrb1
- Phenotype
- 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; muscle 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); 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; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory 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);
Zebrafish Information Network
- Gene name
- arrb1
- Affected structure
- nucleate erythrocyte
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- activation of MAPK activity;positive regulation of protein phosphorylation;G protein-coupled receptor internalization;positive regulation of receptor internalization;transcription by RNA polymerase II;ubiquitin-dependent protein catabolic process;apoptotic process;G protein-coupled receptor signaling pathway;phototransduction;positive regulation of cell population proliferation;protein transport;protein ubiquitination;histone acetylation;platelet activation;negative regulation of protein ubiquitination;positive regulation of protein ubiquitination;negative regulation of NF-kappaB transcription factor activity;positive regulation of protein binding;negative regulation of interleukin-6 production;negative regulation of interleukin-8 production;positive regulation of peptidyl-serine phosphorylation;negative regulation of GTPase activity;positive regulation of smooth muscle cell apoptotic process;positive regulation of Rho protein signal transduction;positive regulation of histone acetylation;positive regulation of insulin secretion involved in cellular response to glucose stimulus;response to drug;follicle-stimulating hormone signaling pathway;stress fiber assembly;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;proteasome-mediated ubiquitin-dependent protein catabolic process;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;negative regulation of neuron apoptotic process;positive regulation of GTPase activity;negative regulation of Notch signaling pathway;positive regulation of transcription by RNA polymerase II;membrane organization;negative regulation of ERK1 and ERK2 cascade;positive regulation of ERK1 and ERK2 cascade;positive regulation of histone H4 acetylation
- Cellular component
- Golgi membrane;chromatin;nucleus;nucleoplasm;cytoplasm;lysosomal membrane;endosome;cytosol;plasma membrane;clathrin-coated pit;postsynaptic density;basolateral plasma membrane;nuclear body;cytoplasmic vesicle membrane;pseudopodium;cytoplasmic vesicle;dendritic spine;postsynaptic membrane
- Molecular function
- histone acetyltransferase activity;enzyme inhibitor activity;GTPase activator activity;insulin-like growth factor receptor binding;protein binding;transcription factor binding;estrogen receptor binding;mitogen-activated protein kinase kinase binding;ubiquitin protein ligase binding;alpha-1A adrenergic receptor binding;alpha-1B adrenergic receptor binding;angiotensin receptor binding;follicle-stimulating hormone receptor binding;V2 vasopressin receptor binding;AP-2 adaptor complex binding;clathrin adaptor activity;cysteine-type endopeptidase inhibitor activity involved in apoptotic process;transcription regulatory region DNA binding;ion channel binding;protein phosphorylated amino acid binding;arrestin family protein binding