AP2B1

Summary

AP2B1 (adaptor related protein complex 2 subunit beta 1, HGNC:563) is a protein-coding gene on chromosome 17q12, encoding AP-2 complex subunit beta (P63010). Component of the adaptor protein complex 2 (AP-2).

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.

Source: NCBI Gene 163 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 82 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001030006

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:563
Approved symbol	AP2B1
Name	adaptor related protein complex 2 subunit beta 1
Location	17q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000006125
Ensembl biotype	protein_coding
OMIM	601025
Entrez	163

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 28 protein_coding, 5 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000587805, ENST00000588093, ENST00000588116, ENST00000589774, ENST00000590432, ENST00000590538, ENST00000591561, ENST00000591610, ENST00000592167, ENST00000593014, ENST00000610402, ENST00000612035, ENST00000612116, ENST00000614600, ENST00000616681, ENST00000616784, ENST00000618940, ENST00000619183, ENST00000620039, ENST00000621668, ENST00000621914, ENST00000628168, ENST00000879019, ENST00000879020, ENST00000879021, ENST00000879022, ENST00000879023, ENST00000879024, ENST00000879025, ENST00000879026, ENST00000938755, ENST00000938756, ENST00000938757, ENST00000967994, ENST00000967995, ENST00000967996

RefSeq mRNA: 2 — MANE Select: NM_001030006 NM_001030006, NM_001282

CCDS: CCDS32621, CCDS32622

Canonical transcript exons

ENST00000610402 — 22 exons

Exon	Start	End
ENSE00002841129	35587322	35587428
ENSE00003460066	35594008	35594067
ENSE00003470519	35639595	35639760
ENSE00003480207	35636341	35636456
ENSE00003546540	35605705	35605840
ENSE00003560733	35598230	35598335
ENSE00003570401	35627631	35627726
ENSE00003617746	35641877	35641975
ENSE00003712929	35650530	35650789
ENSE00003714999	35627385	35627505
ENSE00003719631	35709224	35709308
ENSE00003720451	35608142	35608387
ENSE00003725039	35710234	35710320
ENSE00003725874	35682695	35682824
ENSE00003733572	35626621	35626842
ENSE00003733683	35624397	35624587
ENSE00003737805	35671754	35671900
ENSE00003737968	35723625	35726413
ENSE00003742048	35674176	35674321
ENSE00003753532	35717195	35717349
ENSE00003786669	35670857	35670898
ENSE00003787704	35657599	35657791

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 98.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 73.9064 / max 1751.1409, expressed in 1823 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160360	60.7003	1819
160364	5.5552	1473
160363	3.7408	1407
160362	2.3296	1277
160361	1.1708	869
160365	0.3984	168
160366	0.0112	3

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.93	gold quality
ganglionic eminence	UBERON:0004023	98.16	gold quality
ventricular zone	UBERON:0003053	97.89	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.58	gold quality
islet of Langerhans	UBERON:0000006	97.50	gold quality
prefrontal cortex	UBERON:0000451	97.32	gold quality
stromal cell of endometrium	CL:0002255	97.17	gold quality
rectum	UBERON:0001052	97.15	gold quality
right frontal lobe	UBERON:0002810	97.04	gold quality
cingulate cortex	UBERON:0003027	96.80	gold quality
anterior cingulate cortex	UBERON:0009835	96.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.43	gold quality
right lung	UBERON:0002167	96.32	gold quality
left testis	UBERON:0004533	96.28	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.28	gold quality
right testis	UBERON:0004534	96.24	gold quality
caudate nucleus	UBERON:0001873	96.22	gold quality
colonic epithelium	UBERON:0000397	96.16	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.15	gold quality
frontal cortex	UBERON:0001870	96.07	gold quality
nucleus accumbens	UBERON:0001882	96.07	gold quality
amygdala	UBERON:0001876	96.02	gold quality
neocortex	UBERON:0001950	96.02	gold quality
embryo	UBERON:0000922	95.86	gold quality
CA1 field of hippocampus	UBERON:0003881	95.81	gold quality
sperm	CL:0000019	95.77	gold quality
hypothalamus	UBERON:0001898	95.75	gold quality
smooth muscle tissue	UBERON:0001135	95.63	gold quality
putamen	UBERON:0001874	95.60	gold quality
cerebellar cortex	UBERON:0002129	95.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

124 targeting AP2B1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-557	99.96	70.01	1640
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606

Literature-anchored findings (GeneRIF, showing 14)

• interactions of the EGF receptor with AP-2 mediated by the receptor 974YRAL and di-leucine motifs may contribute to beta2 tyrosine phosphorylation (PMID:12900408)
• the AP-2 complex is not associated with the endocytosed plasma membrane-associated clathrin (PMID:14530274)
• AP2 regulates thrombin receptor constitutive internalization and endothelial cell resensitization. (PMID:16581796)
• Clathrin, which interacts with the AP2beta-appendage, achieves ligand displacement in vivo by self-polymerisation as the coated pit matures. (PMID:16903783)
• Results suggest that autosomal recessive hypercholesterolemia (ARH) and beta-arrestin depend on a privileged AP2beta2 appendage site for proper cargo recruitment to clathrin bud sites. (PMID:18843039)
• EGFR, fibrillin-2, P-cadherin and AP2beta as biomarkers for rhabdomyosarcoma diagnostics. (PMID:19469909)
• multiple interactions between PIPKI gamma-p90 and AP-2 lead to spatiotemporally controlled PI(4,5)P(2) synthesis during clathrin-mediated synaptic vesicle endocytosis (PMID:19903820)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• this study determined a structure of AP2 that includes the clathrin-binding beta2 hinge. (PMID:25061211)
• Reduced expression of AP-2beta was significantly associated with more advanced hepatocellular carcinoma stages and larger tumor sizes. The overexpression of AP-2beta reduced HCC proliferation, migration, invasion, tumor formation and metastasis in vitro and in vivo. Moreover, AP-2beta modulates the levels of epithelial-mesenchymal transition markers through Slug and Snail in hepatocellular carcinoma cell lines and tiss… (PMID:30026878)
• AP2B1 might be associated with the development of nonsyndromic cleft lip with or without cleft palate. (PMID:30411541)
• Prevalence of Polymorphism and Post-Training Expression of ACTN3 (R/X) and ACE (I/D) Genes in CrossFit Athletes. (PMID:36901413)
• Polymorphisms of ACE and thrombophilic genes: risk for recurrent pregnancy loss. (PMID:37977651)
• Principal components analysis to evaluate complex association of polymorphisms in ACE and ACTN3 genes and the extent of cardiovascular adaptive changes in elite athletes. (PMID:38093640)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ap2b1	ENSDARG00000035152
mus_musculus	Ap2b1	ENSMUSG00000035152
rattus_norvegicus	Ap2b1	ENSRNOG00000061543
drosophila_melanogaster	rb	FBGN0003210
caenorhabditis_elegans	apb-3	WBGENE00000163

Paralogs (4): AP1B1 (ENSG00000100280), AP3B2 (ENSG00000103723), AP3B1 (ENSG00000132842), AP4B1 (ENSG00000134262)

Protein

Protein identifiers

AP-2 complex subunit beta — P63010 (reviewed: P63010)

Alternative names: AP105B, Adaptor protein complex AP-2 subunit beta, Adaptor-related protein complex 2 subunit beta, Beta-2-adaptin, Beta-adaptin, Clathrin assembly protein complex 2 beta large chain, Plasma membrane adaptor HA2/AP2 adaptin beta subunit

All UniProt accessions (13): P63010, A0A087WU93, A0A087WXS3, A0A087WYD1, A0A087WZQ6, A0A087X253, A0A140VJE8, K7EJ01, K7EJX1, K7EKZ5, K7EMN7, K7EN71, K7ERB2

UniProt curated annotations — full annotation on UniProt →

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. During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10. 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.

Subunit / interactions. Adaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1). Interacts with EPN1. Interacts with EPS15; clathrin competes with EPS15. Interacts with SNAP91; clathrin competes with SNAP91. Interacts with CLTC; clathrin competes with EPS15, SNAP91 and PIP5K1C. Interacts with LDLRAP1. Interacts with AMPH and BIN1. Interacts with ARF6 (GDP-bound). Interacts (dephosphorylated at Tyr-737) with ARRB1; phosphorylation of AP2B1 at Tyr-737 disrupts the interaction. Interacts with SLC2A8. Interacts with SCYL1 and SCYL2. Interacts with TGFBR1 and TGFBR2. Interacts with PIP5K1C; clathrin competes with PIP5K1C. Interacts with DENND1B, but not with DENND1A, nor DENND1C. Interacts with FCHO1. Interacts with RFTN1. Interacts with KIAA1107. Together with AP2A1 or AP2A2 and AP2M1, it interacts with ADAM10; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons.

Subcellular location. Cell membrane. Membrane. Coated pit.

Tissue specificity. Expressed in the brain (at protein level).

Post-translational modifications. Phosphorylation at Tyr-737 by SRC occurs at the plasma membrane in clathrin-coated vesicles (CCVs).

Miscellaneous. Highly expressed in the testis, spleen, thymus, prostate, ovary, blood leukocyte and brain, but not in the heart, placenta, lung, liver, skeletal muscle, kidney and pancreas. Testis expression is restricted to germ cells and is about 3-fold higher in adults than in embryos.

Similarity. Belongs to the adaptor complexes large subunit family.

Isoforms (3)

UniProt ID	Names	Canonical?
P63010-1	1	yes
P63010-2	2
P63010-3	3, Ap2beta-NY

RefSeq proteins (2): NP_001025177, NP_001273 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000225	Armadillo	Repeat
IPR002553	Clathrin/coatomer_adapt-like_N	Domain
IPR008152	Clathrin_a/b/g-adaptin_app_Ig	Domain
IPR009028	Coatomer/calthrin_app_sub_C	Homologous_superfamily
IPR011989	ARM-like	Homologous_superfamily
IPR012295	TBP_dom_sf	Homologous_superfamily
IPR013037	Clathrin_b-adaptin_app_Ig-like	Homologous_superfamily
IPR013041	Clathrin_app_Ig-like_sf	Homologous_superfamily
IPR015151	B-adaptin_app_sub_C	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR016342	AP_complex_bsu_1_2_4	Family
IPR026739	AP_beta	Family

Pfam: PF01602, PF02883, PF09066

UniProt features (102 total): helix 48, strand 22, turn 12, mutagenesis site 10, modified residue 5, splice variant 2, initiator methionine 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
2G30	X-RAY DIFFRACTION	1.6
1E42	X-RAY DIFFRACTION	1.7
5M5R	X-RAY DIFFRACTION	1.76
2IV9	X-RAY DIFFRACTION	1.9
6QH5	X-RAY DIFFRACTION	2.56
2VGL	X-RAY DIFFRACTION	2.6
4UQI	X-RAY DIFFRACTION	2.79
2IV8	X-RAY DIFFRACTION	2.8
7OHO	X-RAY DIFFRACTION	2.88
2JKR	X-RAY DIFFRACTION	2.98
6URI	X-RAY DIFFRACTION	3
2XA7	X-RAY DIFFRACTION	3.1
7OG1	X-RAY DIFFRACTION	3.25
2JKT	X-RAY DIFFRACTION	3.4
6QH7	X-RAY DIFFRACTION	3.4
6YAE	ELECTRON MICROSCOPY	3.9
7Z5C	ELECTRON MICROSCOPY	4.16
6QH6	X-RAY DIFFRACTION	5
6YAF	ELECTRON MICROSCOPY	9.1
6YAI	ELECTRON MICROSCOPY	9.2
6YAH	ELECTRON MICROSCOPY	10.2
7OM8	ELECTRON MICROSCOPY	10.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P63010-F1	83.48	0.62

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 2, 4, 265, 737, 928

Mutagenesis-validated functional residues (10):

Position	Phenotype
815	strongly reduces interaction with snap91, eps15, amph and bin1 and clathrin heavy chain.
841	abolishes interaction with ldlrap1 and arrb1. greatly reduces dennd1b-binding.
842	strongly reduces interaction with arrb1.
849	strongly reduces interaction with ldlrap1, arrb1 and epn1. no effect on dennd1b-binding.
851	strongly reduces interaction with arrb1.
879	no effect on interaction with arrb1.
879	strongly reduces interaction with epn1. reduces interaction with snap91 and clathrin. no effect on eps15 binding.
888	strongly reduces interaction with snap91, epn1 and clathrin. no effect on eps15 binding. abolishes interaction with arrb
902	strongly reduces interaction with ldlrap1 and arrb1. no effect on dennd1b-binding.
917	strongly reduces interaction with ldlrap1. snap91 and clathrin. reduces interaction with epn1. no effect on eps15 bindin

Function

Pathways and Gene Ontology

Reactome pathways

42 pathways

ID	Pathway
R-HSA-167590	Nef Mediated CD4 Down-regulation
R-HSA-177504	Retrograde neurotrophin signalling
R-HSA-182218	Nef Mediated CD8 Down-regulation
R-HSA-2132295	MHC class II antigen presentation
R-HSA-3928665	EPH-ephrin mediated repulsion of cells
R-HSA-437239	Recycling pathway of L1
R-HSA-5099900	WNT5A-dependent internalization of FZD4
R-HSA-5140745	WNT5A-dependent internalization of FZD2, FZD5 and ROR2
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-8866427	VLDLR internalisation and degradation
R-HSA-8964038	LDL clearance
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9918485	Dengue Virus Attachment and Entry
R-HSA-416993	Trafficking of GluR2-containing AMPA receptors
R-HSA-1266738	Developmental Biology
R-HSA-1280218	Adaptive Immune System
R-HSA-162582	Signal Transduction
R-HSA-162906	HIV Infection
R-HSA-162909	Host Interactions of HIV factors
R-HSA-1643685	Disease
R-HSA-164938	Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters
R-HSA-164952	The role of Nef in HIV-1 replication and disease pathogenesis
R-HSA-166520	Signaling by NTRKs
R-HSA-168256	Immune System
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-187037	Signaling by NTRK1 (TRKA)
R-HSA-195721	Signaling by WNT
R-HSA-199991	Membrane Trafficking
R-HSA-2682334	EPH-Ephrin signaling

MSigDB gene sets: 338 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, REACTOME_RETROGRADE_NEUROTROPHIN_SIGNALLING, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, TGCGCANK_UNKNOWN, GOBP_CORONARY_VASCULATURE_DEVELOPMENT, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, CMYB_01, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_ARTERY_DEVELOPMENT

GO Biological Process (18): kidney development (GO:0001822), ventricular septum development (GO:0003281), intracellular protein transport (GO:0006886), neurotransmitter secretion (GO:0007269), vesicle-mediated transport (GO:0016192), aorta development (GO:0035904), positive regulation of endocytosis (GO:0045807), clathrin coat assembly (GO:0048268), synaptic vesicle endocytosis (GO:0048488), coronary vasculature development (GO:0060976), clathrin-dependent endocytosis (GO:0072583), postsynaptic neurotransmitter receptor internalization (GO:0098884), positive regulation of protein localization to membrane (GO:1905477), cardiac septum development (GO:0003279), endocytosis (GO:0006897), chemical synaptic transmission (GO:0007268), heart development (GO:0007507), protein transport (GO:0015031)

GO Molecular Function (5): signal sequence receptor activity (GO:0005048), clathrin binding (GO:0030276), protein-containing complex binding (GO:0044877), protein binding (GO:0005515), clathrin-cargo adaptor activity (GO:0035615)

GO Cellular Component (22): cytosol (GO:0005829), plasma membrane (GO:0005886), synaptic vesicle (GO:0008021), cytoplasmic side of plasma membrane (GO:0009898), membrane (GO:0016020), AP-2 adaptor complex (GO:0030122), clathrin adaptor complex (GO:0030131), endocytic vesicle membrane (GO:0030666), clathrin-coated endocytic vesicle membrane (GO:0030669), endolysosome membrane (GO:0036020), clathrin-coated endocytic vesicle (GO:0045334), postsynaptic endocytic zone (GO:0098843), extrinsic component of presynaptic endocytic zone membrane (GO:0098894), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), clathrin-coated pit (GO:0005905), endomembrane system (GO:0012505), membrane coat (GO:0030117), clathrin coat (GO:0030118), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	2
PCP/CE pathway	2
Plasma lipoprotein clearance	2
Signaling by NTRK1 (TRKA)	1
Adaptive Immune System	1
EPH-Ephrin signaling	1
L1CAM interactions	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
SARS-CoV Infections	1
Dengue Virus Infection	1
Trafficking of AMPA receptors	1
Immune System	1
Viral Infection Pathways	1
HIV Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
animal organ development	2
intracellular protein localization	2
presynapse	2
transport	2
binding	2
cytoplasm	2
membrane	2
plasma membrane	2
clathrin coat	2
endocytic vesicle	2
renal system development	1
cardiac ventricle development	1
cardiac septum development	1
protein transport	1
intracellular transport	1
neurotransmitter transport	1
chemical synaptic transmission	1
establishment of localization in cell	1
signal release from synapse	1
cellular process	1
artery development	1
endocytosis	1
regulation of endocytosis	1
positive regulation of transport	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
synaptic vesicle recycling	1
presynaptic endocytosis	1
blood vessel development	1
heart development	1
receptor-mediated endocytosis	1
regulation of postsynaptic membrane neurotransmitter receptor levels	1
neurotransmitter receptor internalization	1
postsynaptic endocytosis	1
positive regulation of cellular process	1
protein localization to membrane	1
positive regulation of protein localization	1
regulation of protein localization to membrane	1
cardiac chamber development	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

290 interactions, top by confidence:

A	B	Type	Score
GRB2	EGFR	psi-mi:“MI:0914”(association)	0.980
AP2M1	AP2B1	psi-mi:“MI:0915”(physical association)	0.810
AP2B1	LDLRAP1	psi-mi:“MI:0915”(physical association)	0.760
AP2B1	ITSN1	psi-mi:“MI:0407”(direct interaction)	0.760
AP2B1	AP1M2	psi-mi:“MI:0915”(physical association)	0.740
AP1M2	AP2B1	psi-mi:“MI:0915”(physical association)	0.740
AMPH	BIN1	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
AP2B1	Ap2m1	psi-mi:“MI:0915”(physical association)	0.680
AP2B1	SLC25A6	psi-mi:“MI:0915”(physical association)	0.670
AP2B1	THAP1	psi-mi:“MI:0915”(physical association)	0.670
SLC25A6	AP2B1	psi-mi:“MI:0915”(physical association)	0.670
THAP1	AP2B1	psi-mi:“MI:0915”(physical association)	0.670
AP2B1	AP1M1	psi-mi:“MI:0915”(physical association)	0.670
Ap2a2	Ap2s1	psi-mi:“MI:0915”(physical association)	0.660
AP2S1	AP2A2	psi-mi:“MI:0914”(association)	0.640
ITSN1	AP2S1	psi-mi:“MI:0914”(association)	0.640
AP2B1	Ap2a2	psi-mi:“MI:0914”(association)	0.590
Ap2a2	Ap2s1	psi-mi:“MI:0407”(direct interaction)	0.590
Ap2a2	Ap2s1	psi-mi:“MI:0914”(association)	0.590
Ap2a2	Ap2s1	psi-mi:“MI:0915”(physical association)	0.590
AP2B1		psi-mi:“MI:0915”(physical association)	0.560

BioGRID (601): PIP5K1C (Affinity Capture-Western), SLC25A6 (Two-hybrid), KPNA2 (Two-hybrid), U2AF1 (Two-hybrid), AP1M2 (Two-hybrid), RAPGEF3 (Two-hybrid), TXN2 (Two-hybrid), AFF4 (Two-hybrid), THAP1 (Two-hybrid), XRCC6BP1 (Two-hybrid), NEU4 (Two-hybrid), AP2B1 (Affinity Capture-MS), AP2B1 (Affinity Capture-MS), AP2B1 (Affinity Capture-MS), AP2B1 (Affinity Capture-MS)

ESM2 similar proteins: A1A4R8, B0BNG0, B3DNN5, E7F590, F8VPK0, O89079, P45432, P49754, P62944, P63009, P63010, Q12996, Q15006, Q28G25, Q2KJ25, Q4QR29, Q5E993, Q5F3K0, Q5KU39, Q5M7J9, Q5R4J9, Q5R882, Q5RBI3, Q5RDW9, Q60445, Q62018, Q6DEU9, Q6DFB8, Q6INS3, Q6N069, Q6PD62, Q6PGP7, Q6TGY8, Q80UM3, Q8AVU9, Q8BGZ4, Q8TAM2, Q8VD72, Q8VY89, Q8VZM1

Diamond homologs: O35643, O43005, O43079, O81742, P27351, P36000, P52303, P62944, P63009, P63010, Q08DS7, Q10567, Q13367, Q54X82, Q9DBG3, Q9LDK9, Q9SUS3, Q9WV76, Q9Y6B7, O00203, Q32PG1, Q7YRF1, Q9JME5, Q9Z1T1, Q54R84

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SRC	down-regulates	AP2B1	phosphorylation
AP2B1	“form complex”	“AP-2 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 191 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
WNT5A-dependent internalization of FZD4	8	50.3×	1e-10
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	7	36.7×	3e-08
The role of Nef in HIV-1 replication and disease pathogenesis	7	36.7×	3e-08
VLDLR internalisation and degradation	6	35.4×	5e-07
LDL clearance	7	31.5×	1e-07
Host Interactions of HIV factors	8	22.2×	1e-07
Golgi Associated Vesicle Biogenesis	13	21.5×	4e-12
Plasma lipoprotein clearance	5	19.7×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
clathrin coat assembly	9	53.6×	3e-11
clathrin-dependent endocytosis	9	35.1×	1e-09
synaptic vesicle endocytosis	9	26.1×	2e-08
negative regulation of protein localization to plasma membrane	5	20.9×	5e-04
receptor internalization	6	13.1×	8e-04
insulin receptor signaling pathway	6	8.9×	5e-03
vesicle-mediated transport	12	7.8×	1e-05
endocytosis	12	7.7×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

82 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	49
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3243102	NC_000017.10:g.(?33445500)(34079869_?)del	Pathogenic

SpliceAI

4087 predictions. Top by Δscore:

Variant	Effect	Δscore
17:35587427:CGG:C	donor_loss	1.0000
17:35594002:CTATA:C	acceptor_loss	1.0000
17:35594005:TAG:T	acceptor_loss	1.0000
17:35594006:A:AC	acceptor_loss	1.0000
17:35594065:AAGGT:A	donor_loss	1.0000
17:35594066:AGGT:A	donor_loss	1.0000
17:35594068:G:C	donor_loss	1.0000
17:35594069:T:A	donor_loss	1.0000
17:35598224:TTGCA:T	acceptor_loss	1.0000
17:35598225:TGCA:T	acceptor_loss	1.0000
17:35598226:GCAGG:G	acceptor_loss	1.0000
17:35598227:CA:C	acceptor_loss	1.0000
17:35598227:CAGG:C	acceptor_gain	1.0000
17:35598228:A:AG	acceptor_gain	1.0000
17:35598228:AG:A	acceptor_gain	1.0000
17:35598228:AGGA:A	acceptor_gain	1.0000
17:35598229:G:GC	acceptor_gain	1.0000
17:35598229:G:T	acceptor_loss	1.0000
17:35598229:GG:G	acceptor_gain	1.0000
17:35598229:GGA:G	acceptor_gain	1.0000
17:35598229:GGAG:G	acceptor_gain	1.0000
17:35598229:GGAGA:G	acceptor_gain	1.0000
17:35598328:GATGT:G	donor_gain	1.0000
17:35598331:GTTAG:G	donor_gain	1.0000
17:35598336:G:GG	donor_gain	1.0000
17:35598336:G:T	donor_loss	1.0000
17:35598337:T:A	donor_loss	1.0000
17:35605703:A:AG	acceptor_gain	1.0000
17:35605704:G:GA	acceptor_gain	1.0000
17:35605704:GT:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000079994 (17:35597585 T>C), RS1000113351 (17:35589236 T>G), RS1000140667 (17:35641184 A>G), RS1000156535 (17:35609522 A>G), RS1000157716 (17:35664512 C>G,T), RS1000187590 (17:35684862 G>A), RS1000228324 (17:35620175 T>C), RS1000247130 (17:35613834 T>C,G), RS1000255992 (17:35634690 T>C), RS1000269282 (17:35707535 C>T), RS1000286224 (17:35645025 C>G), RS1000404600 (17:35585611 T>G), RS1000429221 (17:35628532 G>A), RS1000448187 (17:35681231 C>A), RS1000465119 (17:35628856 T>A,G)

Disease associations

OMIM: gene MIM:601025 | disease phenotypes: MIM:614859

GenCC curated gene-disease

Mondo (1): peroxisome biogenesis disorder 3A (Zellweger) (MONDO:0013927)

Orphanet (1): Zellweger syndrome (Orphanet:912)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST001335_29	Mean platelet volume	4.000000e-12
GCST001337_51	Platelet count	2.000000e-14
GCST004599_122	Mean platelet volume	5.000000e-38
GCST004603_180	Platelet count	1.000000e-40
GCST004611_218	High light scatter reticulocyte count	2.000000e-39
GCST004611_219	High light scatter reticulocyte count	2.000000e-28
GCST004612_208	High light scatter reticulocyte percentage of red cells	6.000000e-42
GCST004612_209	High light scatter reticulocyte percentage of red cells	3.000000e-29
GCST004616_29	Platelet distribution width	1.000000e-99
GCST004616_30	Platelet distribution width	8.000000e-12
GCST004619_133	Reticulocyte fraction of red cells	1.000000e-130
GCST004619_30	Reticulocyte fraction of red cells	2.000000e-81
GCST004622_50	Reticulocyte count	7.000000e-76
GCST004622_51	Reticulocyte count	5.000000e-119
GCST007001_12	Cerebrospinal AB1-42 levels in normal cognition	4.000000e-07
GCST007576_45	Chronotype	3.000000e-11
GCST008595_212	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	2.000000e-09
GCST90002385_412	High light scatter reticulocyte count	3.000000e-55
GCST90002386_184	High light scatter reticulocyte percentage of red cells	1.000000e-56
GCST90002387_28	Immature fraction of reticulocytes	2.000000e-11
GCST90002395_252	Mean platelet volume	3.000000e-12
GCST90002396_617	Mean reticulocyte volume	5.000000e-09
GCST90002405_403	Reticulocyte count	8.000000e-101
GCST90002406_458	Reticulocyte fraction of red cells	8.000000e-118
GCST90002406_459	Reticulocyte fraction of red cells	8.000000e-11

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007986	reticulocyte count
EFO:0007984	platelet component distribution width
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0008328	chronotype measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566633	Peroxisome Biogenesis Disorder, Complementation Group 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067269 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.48	Kd	331.3	nM	CHEMBL5653589
6.48	ED50	331.3	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147865: Binding affinity to human AP2B1 incubated for 45 mins by Kinobead based pull down assay	kd	0.3313	uM

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, increases expression	3
bisphenol A	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
coumarin	decreases phosphorylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Irinotecan	decreases expression	1
Arsenic Trioxide	decreases reaction, affects binding	1
Acrolein	affects cotreatment, increases oxidation	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Aspirin	decreases expression	1
Cadmium	decreases expression	1
Dinitrochlorobenzene	affects binding	1
Gasoline	increases abundance, increases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Lead	affects expression, affects splicing	1
Nickel	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650907	Binding	Binding affinity to human AP2B1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.