AP2A1

adaptor related protein complex 2 subunit alpha 1, the group of Clathrin/coatomer adaptor, adaptin-like, N-terminal domain containing|Adaptor related protein complex 2|MicroRNA protein coding host genes

Basic information

Region (hg38): 19:49767001-49807114

Previous symbols: [ "CLAPA1", "ADTAA" ]

Links

ENSG00000196961 ∙ NCBI:160 ∙ OMIM:601026 ∙ HGNC:561 ∙ Uniprot:O95782 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AP2A1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AP2A1 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			37			37
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	37	0	1

Variants in AP2A1

This is a list of pathogenic ClinVar variants found in the AP2A1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-49782067-A-G		not specified	Uncertain significance (Jun 29, 2022)
19-49782687-G-A		not specified	Uncertain significance (Feb 22, 2024)
19-49782696-G-A		not specified	Uncertain significance (May 13, 2024)
19-49792991-G-T		not specified	Uncertain significance (Oct 12, 2021)
19-49792992-G-A		not specified	Uncertain significance (Feb 21, 2024)
19-49793001-C-T		not specified	Uncertain significance (Jun 01, 2023)
19-49793009-G-A		not specified	Uncertain significance (Jul 29, 2023)
19-49793058-C-T		not specified	Uncertain significance (Jun 17, 2024)
19-49795678-G-A		not specified	Uncertain significance (Dec 05, 2022)
19-49795703-A-T		not specified	Uncertain significance (Oct 11, 2024)
19-49795704-G-T		not specified	Uncertain significance (Aug 17, 2021)
19-49795712-G-A		not specified	Uncertain significance (Aug 31, 2023)
19-49795730-C-T		not specified	Uncertain significance (Feb 10, 2022)
19-49795732-C-A		not specified	Uncertain significance (Nov 13, 2024)
19-49798823-G-A		not specified	Uncertain significance (Aug 17, 2022)
19-49798946-A-G		not specified	Uncertain significance (Oct 26, 2021)
19-49799425-C-T		not specified	Uncertain significance (Jan 09, 2024)
19-49799444-C-G		not specified	Uncertain significance (Sep 09, 2024)
19-49799456-C-T			Benign (Jul 05, 2018)
19-49799651-G-A		not specified	Uncertain significance (Jan 26, 2022)
19-49799681-T-C		not specified	Uncertain significance (Nov 08, 2024)
19-49799714-C-T		not specified	Uncertain significance (Mar 14, 2023)
19-49799737-A-G		not specified	Uncertain significance (May 23, 2023)
19-49800973-C-T		not specified	Uncertain significance (Jun 21, 2023)
19-49801390-C-T		not specified	Likely benign (Dec 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AP2A1	protein_coding	protein_coding	ENST00000359032	24	40146

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.14e-7	124910	0	5	124915	0.0000200

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.40	300	604	0.497	0.0000395	6245
Missense in Polyphen		60	214.57	0.27963		2272
Synonymous	1.42	245	275	0.891	0.0000202	1957
Loss of Function	6.22	1	47.0	0.0213	0.00000234	527

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000590	0.0000590
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000269	0.0000265
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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: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);miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in squamous cell - TarBase;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;endocytotic role of ndk phosphins and dynamin;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;Transport of small molecules;Neuronal System;Clathrin-mediated endocytosis;Signaling by NTRK1 (TRKA);WNT5A-dependent internalization of FZD4;PCP/CE pathway;Signaling by NTRKs;EGFR1;Beta-catenin independent WNT signaling;-arrestins in gpcr desensitization;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;Arf1 pathway;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: 0.358

Intolerance Scores

• loftool: 0.142
• rvis_EVS: -1.46
• rvis_percentile_EVS: 3.78

Haploinsufficiency Scores

• pHI: 0.115
• hipred: Y
• hipred_score: 0.785
• ghis: 0.663

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.978

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ap2a1

Zebrafish Information Network

• Gene name: ap2a1
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: broken

Gene ontology

• Biological process: intracellular protein transport;Golgi to endosome transport;endocytosis;positive regulation of neuron projection 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;ephrin receptor signaling pathway;positive regulation of receptor-mediated endocytosis;regulation of defense response to virus by virus;Wnt signaling pathway, planar cell polarity pathway;membrane organization;clathrin-dependent endocytosis;negative regulation of hyaluronan biosynthetic process
• Cellular component: cytosol;plasma membrane;membrane;basolateral plasma membrane;apical plasma membrane;AP-2 adaptor complex;clathrin coat of trans-Golgi network vesicle;endocytic vesicle membrane;clathrin-coated endocytic vesicle membrane;filopodium tip;endolysosome membrane;clathrin-coated endocytic vesicle
• Molecular function: protein binding;protein C-terminus binding;protein kinase binding;clathrin adaptor activity;protein-containing complex binding;low-density lipoprotein particle receptor binding