AP2A2

adaptor related protein complex 2 subunit alpha 2, the group of Clathrin/coatomer adaptor, adaptin-like, N-terminal domain containing|Adaptor related protein complex 2

Basic information

Region (hg38): 11:924881-1012245

Previous symbols: [ "CLAPA2", "ADTAB" ]

Links

ENSG00000183020 ∙ NCBI:161 ∙ OMIM:607242 ∙ HGNC:562 ∙ Uniprot:O94973 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• schizophrenia (Limited), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AP2A2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AP2A2 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		1
missense			40	1		41
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	40	2	0

Variants in AP2A2

This is a list of pathogenic ClinVar variants found in the AP2A2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-926026-C-G		not specified	Uncertain significance (Jul 14, 2021)
11-959457-A-C		not specified	Uncertain significance (Nov 29, 2021)
11-959457-A-G		not specified	Uncertain significance (May 26, 2024)
11-959468-A-G		not specified	Uncertain significance (Dec 01, 2022)
11-959496-A-G		not specified	Uncertain significance (Jan 23, 2024)
11-970207-G-A		not specified	Uncertain significance (Dec 16, 2021)
11-970263-G-A		not specified	Uncertain significance (May 24, 2023)
11-972129-T-C		not specified	Uncertain significance (Jun 03, 2022)
11-972188-G-A		not specified	Uncertain significance (Aug 19, 2021)
11-972188-G-T		not specified	Uncertain significance (Jul 09, 2021)
11-977172-C-T		not specified	Uncertain significance (Dec 05, 2022)
11-981270-G-A		not specified	Uncertain significance (Nov 12, 2021)
11-981282-G-A		not specified	Uncertain significance (Jun 06, 2022)
11-985510-A-G		not specified	Uncertain significance (Jan 20, 2023)
11-985569-A-G		not specified	Uncertain significance (Oct 27, 2022)
11-988619-A-G			Likely benign (Feb 01, 2023)
11-992584-A-G		not specified	Uncertain significance (Sep 12, 2023)
11-993293-G-A		not specified	Uncertain significance (Apr 19, 2024)
11-993372-C-T		not specified	Uncertain significance (Jan 29, 2024)
11-993756-C-T		not specified	Uncertain significance (Dec 19, 2022)
11-993803-G-A		not specified	Uncertain significance (Jun 12, 2023)
11-993817-G-A			Likely benign (Jan 01, 2023)
11-993896-G-A		not specified	Uncertain significance (May 07, 2024)
11-993965-G-A		not specified	Uncertain significance (Feb 16, 2023)
11-994092-G-T		not specified	Uncertain significance (Jan 23, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AP2A2	protein_coding	protein_coding	ENST00000448903	22	87346

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.62e-7	124680	0	11	124691	0.0000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.13	362	573	0.632	0.0000369	6053
Missense in Polyphen		70	169.96	0.41186		1845
Synonymous	0.0277	265	266	0.998	0.0000201	1883
Loss of Function	6.01	1	44.0	0.0227	0.00000232	501

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000630	0.0000619
Middle Eastern	0.00	0.00
South Asian	0.0000330	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C- terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity). {ECO:0000250, ECO:0000269|PubMed:12960147, ECO:0000269|PubMed:14745134, 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;Developmental Biology;Neutrophil degranulation;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;Innate Immune System;Immune System;LDL clearance;VLDLR internalisation and degradation;Plasma lipoprotein clearance;Adaptive Immune System;Retrograde neurotrophin signalling;Transport of small molecules;Neuronal System;Clathrin-mediated endocytosis;Signaling by NTRK1 (TRKA);WNT5A-dependent internalization of FZD4;PCP/CE pathway;Signaling by NTRKs;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: 0.152

Intolerance Scores

• loftool: 0.104
• rvis_EVS: -1.77
• rvis_percentile_EVS: 2.3

Haploinsufficiency Scores

• pHI: 0.157
• hipred: Y
• hipred_score: 0.825
• ghis: 0.631

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.933

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ap2a2
• Phenotype: homeostasis/metabolism phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype

Gene ontology

• Biological process: intracellular protein transport;antigen processing and presentation of exogenous peptide antigen via MHC class II;low-density lipoprotein particle receptor catabolic process;low-density lipoprotein particle clearance;neutrophil degranulation;ephrin receptor signaling pathway;regulation of defense response to virus by virus;Wnt signaling pathway, planar cell polarity pathway;membrane organization;clathrin-dependent endocytosis
• Cellular component: cytosol;plasma membrane;AP-2 adaptor complex;endocytic vesicle membrane;secretory granule membrane;clathrin-coated endocytic vesicle membrane;cytoplasmic vesicle;endolysosome membrane;clathrin-coated endocytic vesicle;ficolin-1-rich granule membrane
• Molecular function: molecular_function;protein binding;lipid binding;protein kinase binding;clathrin adaptor activity;disordered domain specific binding