AP2B1
adaptor related protein complex 2 subunit beta 1, the group of Clathrin/coatomer adaptor, adaptin-like, N-terminal domain containing|Adaptor related protein complex 2
Basic information
Region (hg38): 17:35578046-35726413
Previous symbols: [ "ADTB2", "CLAPB1" ]
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 AP2B1 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 | 18 | 18 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 18 | 0 | 1 |
Variants in AP2B1
This is a list of pathogenic ClinVar variants found in the AP2B1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 17-35578047-C-T | Peroxisome biogenesis disorder 3A (Zellweger);Peroxisome biogenesis disorder type 3B • Peroxisome biogenesis disorder 3A (Zellweger) | Uncertain significance (Nov 09, 2021) | ||
| 17-35578129-T-C | Peroxisome biogenesis disorder 3A (Zellweger) | Uncertain significance (Jan 13, 2018) | ||
| 17-35578159-A-G | Peroxisome biogenesis disorder 3A (Zellweger) | Uncertain significance (Jan 13, 2018) | ||
| 17-35578166-G-A | Peroxisome biogenesis disorder 3A (Zellweger) | Uncertain significance (Jan 12, 2018) | ||
| 17-35578168-G-A | Peroxisome biogenesis disorder 3A (Zellweger) | Uncertain significance (Jan 12, 2018) | ||
| 17-35578361-C-A | Peroxisome biogenesis disorder 3A (Zellweger) | Uncertain significance (Jan 13, 2018) | ||
| 17-35578379-C-A | Peroxisome biogenesis disorder 3A (Zellweger) | Uncertain significance (Jan 12, 2018) | ||
| 17-35578381-C-T | Peroxisome biogenesis disorder 3A (Zellweger) | Uncertain significance (Jan 12, 2018) | ||
| 17-35578426-G-C | Peroxisome biogenesis disorder 3A (Zellweger) | Uncertain significance (Jan 13, 2018) | ||
| 17-35578448-C-T | Peroxisome biogenesis disorder 3A (Zellweger) | Uncertain significance (Jan 12, 2018) | ||
| 17-35578449-A-G | Peroxisome biogenesis disorder 3A (Zellweger) | Benign (Aug 07, 2018) | ||
| 17-35578455-T-G | Peroxisome biogenesis disorder 3A (Zellweger) | Uncertain significance (Jan 13, 2018) | ||
| 17-35578516-G-A | Peroxisome biogenesis disorder 3A (Zellweger) | Uncertain significance (Jan 12, 2018) | ||
| 17-35578555-G-A | Peroxisome biogenesis disorder 3A (Zellweger) | Benign (Nov 16, 2018) | ||
| 17-35578726-C-T | Benign (Aug 07, 2018) | |||
| 17-35578961-A-G | Likely benign (Sep 11, 2018) | |||
| 17-35605791-C-G | not specified | Uncertain significance (Jun 29, 2023) | ||
| 17-35605801-G-T | not provided (-) | |||
| 17-35608295-G-A | not specified | Uncertain significance (Aug 28, 2023) | ||
| 17-35624455-A-G | not specified | Uncertain significance (Oct 30, 2023) | ||
| 17-35624468-G-A | Benign (Dec 31, 2019) | |||
| 17-35626761-C-T | not specified | Uncertain significance (Oct 03, 2022) | ||
| 17-35650692-A-G | not specified | Uncertain significance (Feb 07, 2023) | ||
| 17-35650729-A-G | not specified | Uncertain significance (Jul 11, 2022) | ||
| 17-35650776-A-G | not specified | Uncertain significance (Dec 26, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| AP2B1 | protein_coding | protein_coding | ENST00000312678 | 21 | 148372 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.998 | 0.00170 | 125725 | 0 | 23 | 125748 | 0.0000915 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 5.17 | 193 | 527 | 0.366 | 0.0000278 | 6260 |
| Missense in Polyphen | 25 | 132.67 | 0.18844 | 1609 | ||
| Synonymous | 1.11 | 177 | 197 | 0.900 | 0.0000103 | 1869 |
| Loss of Function | 5.39 | 6 | 45.0 | 0.133 | 0.00000217 | 554 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00118 | 0.00109 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000100 | 0.0000967 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000183 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin- coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 beta subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins; at least some clathrin- associated sorting proteins (CLASPs) are recognized by their [DE]- X(1,2)-F-X-X-[FL]-X-X-X-R motif. The AP-2 beta subunit binds to clathrin heavy chain, promoting clathrin lattice assembly; clathrin displaces at least some CLASPs from AP2B1 which probably then can be positioned for further coat assembly. {ECO:0000269|PubMed:14745134, ECO:0000269|PubMed:14985334, ECO:0000269|PubMed:15473838, ECO:0000269|PubMed:19033387}.;
- Pathway
- Synaptic vesicle cycle - Homo sapiens (human);Endocytosis - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human);Synaptic Vesicle Pathway;GABA receptor Signaling;EGF-EGFR Signaling Pathway;Developmental Biology;Disease;Signaling by WNT;Signal Transduction;Recycling pathway of L1;Vesicle-mediated transport;Membrane Trafficking;Host Interactions of HIV factors;HIV Infection;MHC class II antigen presentation;Infectious disease;Immune System;LDL clearance;VLDLR internalisation and degradation;Plasma lipoprotein clearance;Adaptive Immune System;Retrograde neurotrophin signalling;Fibroblast growth factor-1;Transport of small molecules;Neuronal System;Clathrin-mediated endocytosis;Signaling by NTRK1 (TRKA);TGF_beta_Receptor;WNT5A-dependent internalization of FZD4;PCP/CE pathway;Signaling by NTRKs;EGFR1;Beta-catenin independent WNT signaling;Nef Mediated CD4 Down-regulation;Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters;The role of Nef in HIV-1 replication and disease pathogenesis;Plasma lipoprotein assembly, remodeling, and clearance;Cargo recognition for clathrin-mediated endocytosis;Trafficking of GluR2-containing AMPA receptors;Trafficking of AMPA receptors;L1CAM interactions;Glutamate binding, activation of AMPA receptors and synaptic plasticity;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Axon guidance;Signaling by Receptor Tyrosine Kinases;Nef Mediated CD8 Down-regulation
(Consensus)
Recessive Scores
- pRec
- 0.313
Intolerance Scores
- loftool
- 0.156
- rvis_EVS
- -0.96
- rvis_percentile_EVS
- 9.09
Haploinsufficiency Scores
- pHI
- 0.718
- hipred
- Y
- hipred_score
- 0.717
- ghis
- 0.532
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.927
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ap2b1
- Phenotype
- endocrine/exocrine gland phenotype; growth/size/body region phenotype; craniofacial phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); digestive/alimentary phenotype; skeleton phenotype;
Gene ontology
- Biological process
- ventricular septum development;antigen processing and presentation of exogenous peptide antigen via MHC class II;low-density lipoprotein particle receptor catabolic process;low-density lipoprotein particle clearance;aorta development;positive regulation of endocytosis;ephrin receptor signaling pathway;clathrin coat assembly;regulation of defense response to virus by virus;Wnt signaling pathway, planar cell polarity pathway;coronary vasculature development;membrane organization;clathrin-dependent endocytosis;postsynaptic neurotransmitter receptor internalization;negative regulation of neuron death;positive regulation of protein localization to membrane
- Cellular component
- cytosol;plasma membrane;membrane;AP-2 adaptor complex;endocytic vesicle membrane;clathrin-coated endocytic vesicle membrane;endolysosome membrane;clathrin-coated endocytic vesicle;postsynapse;glutamatergic synapse
- Molecular function
- signal sequence binding;protein binding;clathrin binding;clathrin adaptor activity;protein-containing complex binding