AP2B1
protein-codingadaptor related protein complex 2 subunit beta 1, the group of Clathrin/coatomer adaptor, adaptin-like, N-terminal domain containing|Adaptor related protein complex 2
Gene summary
The protein encoded by this gene is one of two large chain components of the assembly protein complex 2, which serves to link clathrin to receptors in coated vesicles. The encoded protein is found on the cytoplasmic face of coated vesicles in the plasma membrane. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
- ADTB2
- CLAPB1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~148.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to AP2B1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001030006.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 1 | 5 | |||
| missense | 52 | 52 | ||||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 64 | 0 | 1 | 65 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001025177.1 | 21 | MANE Select | |
| Ensembl | ENSP00000483185.1 | 21 | MANE Select | |
| RefSeq | NP_001273.1 | 20 | Standard | |
| Ensembl | ENSP00000466580.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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
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
Molecular Function
- signal sequence binding
- protein binding
- clathrin binding
- clathrin adaptor activity
- protein-containing complex binding
Cellular Component
- cytosol
- plasma membrane
- membrane
- AP-2 adaptor complex
- endocytic vesicle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000312678
- Coding exons
- 21
- Length
- 148372
- Individuals with no LoFs
- 125725
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 23
- Defined
- 125748
- p
- 0.0000915
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 5.17 | 193 | 527 | 0.366 | 0.0000278 | 6260 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.0012 | 0.0011 | notable |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00010 | 0.000097 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00018 | 0.00016 | rare |
dbNSFP Gene Annotations
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}.;
Recessive Scores
- pRec
- 0.313
Intolerance Scores
- LoFtool
- 0.156
- RVIS EVS
- -0.96
- RVIS percentile EVS
- 9.09
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.927
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |