AP3B2

Summary

AP3B2 (adaptor related protein complex 3 subunit beta 2, HGNC:567) is a protein-coding gene on chromosome 15q25.2, encoding AP-3 complex subunit beta-2 (Q13367). Subunit of non-clathrin- and clathrin-associated adaptor protein complex 3 (AP-3) that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes.

Adaptor protein complex 3 (AP-3 complex) is a heterotrimeric protein complex involved in the formation of clathrin-coated synaptic vesicles. The protein encoded by this gene represents the beta subunit of the neuron-specific AP-3 complex and was first identified as the target antigen in human paraneoplastic neurologic disorders. The encoded subunit binds clathrin and is phosphorylated by a casein kinase-like protein, which mediates synaptic vesicle coat assembly. Defects in this gene are a cause of early-onset epileptic encephalopathy.

Source: NCBI Gene 8120 — RefSeq curated summary.

At a glance

• Gene–disease (curated): genetic developmental and epileptic encephalopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 890 total — 28 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 66
• MANE Select transcript: NM_001278512

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:567
Approved symbol	AP3B2
Name	adaptor related protein complex 3 subunit beta 2
Location	15q25.2
Locus type	gene with protein product
Status	Approved
Aliases	NAPTB
Ensembl gene	ENSG00000103723
Ensembl biotype	protein_coding
OMIM	602166
Entrez	8120

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 16 protein_coding, 15 retained_intron, 6 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined

ENST00000261722, ENST00000535348, ENST00000535359, ENST00000535385, ENST00000535513, ENST00000537735, ENST00000541693, ENST00000542200, ENST00000543938, ENST00000559888, ENST00000560529, ENST00000561455, ENST00000642989, ENST00000652847, ENST00000657321, ENST00000659252, ENST00000660624, ENST00000661532, ENST00000663651, ENST00000664460, ENST00000665513, ENST00000666055, ENST00000666672, ENST00000666894, ENST00000666973, ENST00000667758, ENST00000668385, ENST00000668458, ENST00000668990, ENST00000669880, ENST00000669930, ENST00000679388, ENST00000679531, ENST00000679891, ENST00000679950, ENST00000680492, ENST00000680912, ENST00000680946, ENST00000681044, ENST00000681327, ENST00000681452, ENST00000681464

RefSeq mRNA: 4 — MANE Select: NM_001278512 NM_001278511, NM_001278512, NM_001348440, NM_004644

CCDS: CCDS45331, CCDS61736, CCDS61737, CCDS86482

Canonical transcript exons

ENST00000535359 — 27 exons

Exon	Start	End
ENSE00000700749	82681420	82681580
ENSE00000794206	82680175	82680229
ENSE00000794208	82680472	82680755
ENSE00002210902	82665247	82665303
ENSE00002245972	82659281	82659710
ENSE00002323827	82709594	82709875
ENSE00003480377	82662168	82662252
ENSE00003484006	82664835	82664943
ENSE00003487858	82661825	82661922
ENSE00003494810	82664367	82664490
ENSE00003498119	82677671	82677803
ENSE00003520594	82663127	82663233
ENSE00003521273	82680837	82681019
ENSE00003544980	82663801	82663975
ENSE00003548615	82665457	82665575
ENSE00003552687	82677274	82677383
ENSE00003586964	82689378	82689453
ENSE00003590233	82676461	82676637
ENSE00003603669	82681112	82681178
ENSE00003604353	82663560	82663620
ENSE00003605297	82662694	82662922
ENSE00003619623	82688736	82688831
ENSE00003651488	82659845	82659983
ENSE00003652638	82666747	82666933
ENSE00003674197	82689158	82689232
ENSE00003682810	82679729	82679800
ENSE00003694083	82678105	82678167

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 97.82.

FANTOM5 (CAGE): breadth broad, TPM avg 6.1837 / max 235.7156, expressed in 592 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151272	3.1243	491
151273	1.4499	238
151271	0.5896	141
151262	0.4568	22
151265	0.1869	21
151270	0.1001	56
151266	0.0993	61
151269	0.0496	27
151263	0.0399	14
151268	0.0385	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.82	gold quality
cerebellar hemisphere	UBERON:0002245	97.58	gold quality
cerebellar cortex	UBERON:0002129	97.49	gold quality
cerebellum	UBERON:0002037	96.57	gold quality
right frontal lobe	UBERON:0002810	96.03	gold quality
cortical plate	UBERON:0005343	95.20	gold quality
adenohypophysis	UBERON:0002196	95.00	gold quality
pituitary gland	UBERON:0000007	94.60	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.60	gold quality
prefrontal cortex	UBERON:0000451	94.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.66	gold quality
frontal cortex	UBERON:0001870	93.59	gold quality
frontal lobe	UBERON:0016525	93.58	gold quality
cingulate cortex	UBERON:0003027	93.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.33	gold quality
anterior cingulate cortex	UBERON:0009835	93.31	gold quality
neocortex	UBERON:0001950	93.20	gold quality
ganglionic eminence	UBERON:0004023	93.13	gold quality
cerebral cortex	UBERON:0000956	92.00	gold quality
brain	UBERON:0000955	90.98	gold quality
amygdala	UBERON:0001876	90.94	gold quality
nucleus accumbens	UBERON:0001882	90.94	gold quality
forebrain	UBERON:0001890	90.81	gold quality
central nervous system	UBERON:0001017	90.72	gold quality
telencephalon	UBERON:0001893	90.68	gold quality
hypothalamus	UBERON:0001898	90.47	gold quality
CA1 field of hippocampus	UBERON:0003881	89.95	gold quality
superior frontal gyrus	UBERON:0002661	89.66	gold quality
Ammon’s horn	UBERON:0001954	89.64	gold quality
Brodmann (1909) area 46	UBERON:0006483	89.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting AP3B2, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-6894-5P	98.70	63.78	809
HSA-MIR-4712-3P	98.52	65.39	822
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-4521	97.73	67.64	684
HSA-MIR-3126-3P	97.17	66.51	468
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-3616-3P	96.96	65.45	983
HSA-MIR-1343-5P	96.48	66.06	1506
HSA-MIR-1298-3P	94.05	64.84	620

Literature-anchored findings (GeneRIF, showing 7)

• A novel splice variant of AP3B2, AP3B2_v2, was isolated by large-scale sequencing analysis of a fetal brain cDNA library; Sequence analysis showed AP3B2_v2 missed 22 exons that existed in AP3B2_upsilon1, encoding a different putative protein (PMID:17453999)
• Our findings provide direct evidence for the association of FBXO38 and AP3B2 with severe chronic periodontitis in the Han Chinese population. (PMID:26643602)
• Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy. (PMID:27889060)
• The AP3B2 antigen was identified in sera and cerebrospinal fluid of patients with sensory or cerebellar ataxia. (PMID:31371564)
• Blended phenotype of combination of HERC2 and AP3B2 deficiency and Angelman syndrome caused by paternal isodisomy of chromosome 15. (PMID:34042275)
• Plasma lncRNA LOC338963 and mRNA AP3B2 are upregulated in paraneoplastic Lambert-Eaton myasthenic syndrome. (PMID:35508598)
• Novel homozygous AP3B2 mutations in four individuals with developmental and epileptic encephalopathy: A rare clinical entity. (PMID:36356440)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	AP3B2	ENSDARG00000105296
mus_musculus	Ap3b2	ENSMUSG00000062444
rattus_norvegicus	Ap3b2	ENSRNOG00000019249
drosophila_melanogaster	rb	FBGN0003210
caenorhabditis_elegans	apb-3	WBGENE00000163

Paralogs (4): AP2B1 (ENSG00000006125), AP1B1 (ENSG00000100280), AP3B1 (ENSG00000132842), AP4B1 (ENSG00000134262)

Protein

Protein identifiers

AP-3 complex subunit beta-2 — Q13367 (reviewed: Q13367)

Alternative names: Adaptor protein complex AP-3 subunit beta-2, Adaptor-related protein complex 3 subunit beta-2, Beta-3B-adaptin, Clathrin assembly protein complex 3 beta-2 large chain, Neuron-specific vesicle coat protein beta-NAP

All UniProt accessions (19): Q13367, A0A2R8Y2A8, A0A590UJ44, A0A590UJ60, A0A590UJ88, A0A590UJE5, A0A590UJS5, A0A590UJU0, A0A590UJU7, A0A590UJW5, A0A590UK04, A0A590UK30, A0A590UK64, A0A590UK69, A0A590UKC4, A0A590UKD3, A0A5F9UJV3, F5GWU4, F5GYB0

UniProt curated annotations — full annotation on UniProt →

Function. Subunit of non-clathrin- and clathrin-associated adaptor protein complex 3 (AP-3) that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. AP-3 appears to be involved in the sorting of a subset of transmembrane proteins targeted to lysosomes and lysosome-related organelles. In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals.

Subunit / interactions. AP-3 associates with the BLOC-1 complex. Adaptor protein complex 3 (AP-3) is a heterotetramer composed of two large adaptins (delta-type subunit AP3D1 and beta-type subunit AP3B1 or AP3B2), a medium adaptin (mu-type subunit AP3M1 or AP3M2) and a small adaptin (sigma-type subunit APS1 or AP3S2).

Subcellular location. Cytoplasmic vesicle. Clathrin-coated vesicle membrane. Golgi apparatus.

Tissue specificity. Isoform 1 expression is specific to nervous system. Expressed in nerve terminal and cell body, and is associated with nerve-terminal vesicles. Expression seen in Purkinje cells, cortical neurons, neuroectodermal tumors and graded in cerebral cortex (deeper layers exhibit stronger expression). Isoform 2 is expressed at high levels in brain and testis.

Disease relevance. Developmental and epileptic encephalopathy 48 (DEE48) [MIM:617276] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE48 is an autosomal recessive form characterized by onset of seizures in the first year of life. Affected individuals manifest global developmental delay, intellectual disability, absent speech, and poor, if any, motor development. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the adaptor complexes large subunit family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q13367-1	1, AP3B2_v1	yes
Q13367-2	2, AP3B2_v2
Q13367-3	3
Q13367-4	4

RefSeq proteins (4): NP_001265440, NP_001265441, NP_001335369, NP_004635 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002553	Clathrin/coatomer_adapt-like_N	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR013041	Clathrin_app_Ig-like_sf	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR026739	AP_beta	Family
IPR026740	AP3_beta	Family
IPR029390	AP3B_C	Domain
IPR056314	AP3B1/2_C	Domain

Pfam: PF01602, PF14796, PF24080

UniProt features (18 total): compositionally biased region 8, region of interest 3, splice variant 3, modified residue 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13367-F1	75.73	0.44

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 (2): 272, 282

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 260 (showing top): RNGTGGGC_UNKNOWN, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_BEHAVIOR, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_VESICLE_ORGANIZATION, GOBP_ADULT_BEHAVIOR, GOBP_SYNAPTIC_VESICLE_CYTOSKELETAL_TRANSPORT, KEGG_LYSOSOME, KYNG_DNA_DAMAGE_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, GOBP_ADULT_LOCOMOTORY_BEHAVIOR

GO Biological Process (9): intracellular protein transport (GO:0006886), anterograde axonal transport (GO:0008089), synaptic vesicle coating (GO:0016183), vesicle-mediated transport (GO:0016192), clathrin-coated vesicle cargo loading, AP-3-mediated (GO:0035654), synaptic vesicle recycling (GO:0036465), anterograde synaptic vesicle transport (GO:0048490), protein transport (GO:0015031), synaptic vesicle endocytosis (GO:0048488)

GO Molecular Function (1): clathrin binding (GO:0030276)

GO Cellular Component (12): early endosome (GO:0005769), Golgi apparatus (GO:0005794), AP-3 adaptor complex (GO:0030123), clathrin-coated vesicle membrane (GO:0030665), intracellular vesicle (GO:0097708), presynapse (GO:0098793), axon cytoplasm (GO:1904115), endomembrane system (GO:0012505), membrane (GO:0016020), membrane coat (GO:0030117), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
cytoplasm	3
cellular anatomical structure	3
intracellular protein localization	2
intracellular membrane-bounded organelle	2
protein transport	1
intracellular transport	1
axonal transport	1
axon cytoplasm	1
vesicle coat assembly	1
synaptic vesicle budding from presynaptic endocytic zone membrane	1
cellular process	1
clathrin-coated vesicle cargo loading	1
establishment of localization in cell	1
synaptic vesicle cycle	1
anterograde axonal transport	1
synaptic vesicle transport along microtubule	1
establishment of protein localization	1
synaptic vesicle recycling	1
presynaptic endocytosis	1
protein binding	1
endosome	1
endomembrane system	1
AP-type membrane coat adaptor complex	1
clathrin-coated vesicle	1
coated vesicle membrane	1
intracellular anatomical structure	1
vesicle	1
synapse	1
axon	1
neuron projection cytoplasm	1
vacuole	1
plasma membrane	1
coated membrane	1
membrane protein complex	1
vesicle membrane	1
cytoplasmic vesicle	1
intracellular vesicle	1

Protein interactions and networks

STRING

1660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AP3B2	AP4E1	Q9UPM8	763
AP3B2	AP4M1	O00189	722
AP3B2	AP4S1	Q9Y587	718
AP3B2	AP3D1	O14617	644
AP3B2	PLIN1	O60240	642
AP3B2	AP3M1	Q9Y2T2	630
AP3B2	ABHD12B	Q7Z5M8	581
AP3B2	FSD2	A1L4K1	575
AP3B2	NCDN	Q9UBB6	574
AP3B2	WHAMM	Q8TF30	571
AP3B2	AP3M2	P53677	529
AP3B2	HOMER3	Q9NSC5	487
AP3B2	ATP1A3	P13637	478
AP3B2	RUNDC3A	Q59EK9	470
AP3B2	HSPB3	Q12988	468

IntAct

32 interactions, top by confidence:

A	B	Type	Score
AP3M1	AP3B1	psi-mi:“MI:0914”(association)	0.640
AP3S1	AP3B1	psi-mi:“MI:0914”(association)	0.530
EDA	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L3	AP3B1	psi-mi:“MI:0914”(association)	0.530
Dlg4	AP3B2	psi-mi:“MI:0407”(direct interaction)	0.440
AP3B2		psi-mi:“MI:0915”(physical association)	0.370
ERBB2	AP3B2	psi-mi:“MI:0915”(physical association)	0.370
ARRB2		psi-mi:“MI:0914”(association)	0.350
DTNBP1	PARP1	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
EDA	AP3B1	psi-mi:“MI:0914”(association)	0.350
DTNBP1	AP3B1	psi-mi:“MI:0914”(association)	0.350
DAXX	HAT1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CHD8	IGLV4-60	psi-mi:“MI:0914”(association)	0.350
CUL3	KIF21B	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
SYT2	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
SEC62	GPR89A	psi-mi:“MI:0914”(association)	0.350
GPM6A	KIF2A	psi-mi:“MI:0914”(association)	0.350
CREB3L3	AP3B1	psi-mi:“MI:0914”(association)	0.350

BioGRID (46): AP3B2 (Affinity Capture-MS), AP3B2 (Reconstituted Complex), AP3B2 (Affinity Capture-Western), AP3B2 (Affinity Capture-MS), AP3B2 (Affinity Capture-MS), AP3B2 (Affinity Capture-MS), AP3B2 (Affinity Capture-Western), AP3B2 (Affinity Capture-MS), AP3B2 (Affinity Capture-MS), AP3B2 (Affinity Capture-MS), AP3B2 (Affinity Capture-MS), AP3B2 (Affinity Capture-MS), AP3B2 (Co-fractionation), AP3B2 (Affinity Capture-MS), AP3B2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0E0SC50, A1CTJ1, A1D4X8, A1DMW6, A2X052, A4D9P4, A4RN19, A6RA46, A7EAE5, A7EGK5, A7KAM3, B4FTR7, B8AK78, F7W503, O35954, O94817, P0CM28, P0CM29, P49842, P62869, P62870, Q01317, Q0JCC3, Q0UNW1, Q10CI8, Q13367, Q15370, Q1DY54, Q1E8C2, Q2GSG9, Q2TBJ5, Q2UMW6, Q2URI8, Q3T0W7, Q42713, Q43307, Q4WKD7, Q51P78, Q5BCH0, Q5R7W1

Diamond homologs: O00203, O13939, O81742, Q13367, Q32PG1, Q54X82, Q556J8, Q7YRF1, Q9JME5, Q9M2T1, Q9SUS3, Q9Z1T1, O35643, O43005, O43079, P27351, P36000, P52303, P62944, P63009, P63010, Q08DS7, Q10567, Q9DBG3, Q9LDK9, Q9WV76, Q9Y6B7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
AP3B2	“form complex”	“Neuronal AP-3”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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
Membrane Trafficking	6	10.1×	2e-03
Vesicle-mediated transport	6	9.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	28
Likely pathogenic	15
Uncertain significance	348
Likely benign	439
Benign	20

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1031455	NM_001278512.2(AP3B2):c.940C>T (p.Gln314Ter)	Pathogenic
1279926	NM_001278512.2(AP3B2):c.445_448del (p.Ala149fs)	Pathogenic
1369595	NM_001278512.2(AP3B2):c.15del (p.Ala6fs)	Pathogenic
1454093	NM_001278512.2(AP3B2):c.25G>T (p.Glu9Ter)	Pathogenic
1457065	NM_001278512.2(AP3B2):c.826G>T (p.Glu276Ter)	Pathogenic
1694762	NM_001278512.2(AP3B2):c.659del (p.Asn220fs)	Pathogenic
2005892	NM_001278512.2(AP3B2):c.900dup (p.Asp301fs)	Pathogenic
2023943	NM_001278512.2(AP3B2):c.553G>T (p.Glu185Ter)	Pathogenic
2026276	NM_001278512.2(AP3B2):c.3116dup (p.Asn1039fs)	Pathogenic
2098019	NM_001278512.2(AP3B2):c.1291C>T (p.Gln431Ter)	Pathogenic
2121874	NM_001278512.2(AP3B2):c.2452dup (p.Ser818fs)	Pathogenic
2137737	NM_001278512.2(AP3B2):c.281_282del (p.Tyr94fs)	Pathogenic
2425191	NC_000015.9:g.(?83328312)(83621287_?)del	Pathogenic
2435024	NM_001278512.2(AP3B2):c.2929C>T (p.Arg977Ter)	Pathogenic
2577043	NM_001278512.2(AP3B2):c.641delinsATG (p.Ile214fs)	Pathogenic
2579211	GRCh38/hg38 15q25.2(chr15:82130136-82727529)x1	Pathogenic
2749559	NM_001278512.2(AP3B2):c.873dup (p.Ser292fs)	Pathogenic
2815541	NM_001278512.2(AP3B2):c.2046dup (p.Cys683fs)	Pathogenic
2839026	NM_001278512.2(AP3B2):c.877C>T (p.Arg293Ter)	Pathogenic
2982388	NM_001278512.2(AP3B2):c.2095dup (p.Asp699fs)	Pathogenic
3661082	NM_001278512.2(AP3B2):c.1031_1041del (p.Leu344fs)	Pathogenic
3686300	NM_001278512.2(AP3B2):c.2992G>T (p.Glu998Ter)	Pathogenic
374848	NM_001278512.2(AP3B2):c.1489-245_1665+2029del	Pathogenic
374849	NM_001278512.2(AP3B2):c.2579_2582del (p.Leu860fs)	Pathogenic
374850	NM_001278512.2(AP3B2):c.199C>T (p.Arg67Ter)	Pathogenic
374851	NM_001278512.2(AP3B2):c.1837del (p.Glu613fs)	Pathogenic
4714751	NM_001278512.2(AP3B2):c.479dup (p.Tyr160Ter)	Pathogenic
4771713	NM_001278512.2(AP3B2):c.1618C>T (p.Gln540Ter)	Pathogenic
1012860	NM_001278512.2(AP3B2):c.1501C>T (p.Arg501Ter)	Likely pathogenic
1323917	NM_001278512.2(AP3B2):c.454G>T (p.Glu152Ter)	Likely pathogenic

SpliceAI

4838 predictions. Top by Δscore:

Variant	Effect	Δscore
15:82659706:CAAAC:C	acceptor_gain	1.0000
15:82659707:AAAC:A	acceptor_gain	1.0000
15:82659708:AAC:A	acceptor_gain	1.0000
15:82659709:AC:A	acceptor_gain	1.0000
15:82659710:CC:C	acceptor_gain	1.0000
15:82659711:C:CC	acceptor_gain	1.0000
15:82659711:C:T	acceptor_gain	1.0000
15:82659854:T:C	donor_gain	1.0000
15:82661817:GCACT:G	donor_loss	1.0000
15:82661818:CACT:C	donor_loss	1.0000
15:82661819:ACTC:A	donor_loss	1.0000
15:82661820:CT:C	donor_loss	1.0000
15:82661821:TCA:T	donor_loss	1.0000
15:82661822:C:CA	donor_loss	1.0000
15:82661823:A:AC	donor_gain	1.0000
15:82661823:AC:A	donor_gain	1.0000
15:82661823:ACCC:A	donor_loss	1.0000
15:82661824:C:CC	donor_gain	1.0000
15:82661824:C:CG	donor_loss	1.0000
15:82661824:CC:C	donor_gain	1.0000
15:82661919:GGTG:G	acceptor_gain	1.0000
15:82661920:GTG:G	acceptor_gain	1.0000
15:82661921:TG:T	acceptor_gain	1.0000
15:82661923:C:CC	acceptor_gain	1.0000
15:82661932:G:C	acceptor_gain	1.0000
15:82661932:G:GC	acceptor_gain	1.0000
15:82662270:A:T	acceptor_gain	1.0000
15:82662923:C:CC	acceptor_gain	1.0000
15:82663230:GTGA:G	acceptor_gain	1.0000
15:82663231:TGA:T	acceptor_gain	1.0000

AlphaMissense

7199 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:82665468:G:T	R654S	1.000
15:82665498:A:G	W644R	1.000
15:82665498:A:T	W644R	1.000
15:82666860:C:G	R580P	1.000
15:82666861:G:T	R580S	1.000
15:82666866:C:G	R578P	1.000
15:82666869:T:A	D577V	1.000
15:82666869:T:C	D577G	1.000
15:82666869:T:G	D577A	1.000
15:82666870:C:G	D577H	1.000
15:82666872:C:G	R576P	1.000
15:82666873:G:T	R576S	1.000
15:82666899:G:T	A567D	1.000
15:82666902:A:G	L566P	1.000
15:82666908:A:G	L564P	1.000
15:82676483:A:G	L548P	1.000
15:82676493:C:G	A545P	1.000
15:82676495:A:G	L544P	1.000
15:82676512:C:A	K538N	1.000
15:82676512:C:G	K538N	1.000
15:82676516:A:T	V537D	1.000
15:82676537:A:G	F530S	1.000
15:82676554:T:A	R524S	1.000
15:82676554:T:G	R524S	1.000
15:82676555:C:A	R524I	1.000
15:82676555:C:G	R524T	1.000
15:82676606:A:G	L507P	1.000
15:82676608:C:A	W506C	1.000
15:82676608:C:G	W506C	1.000
15:82676610:A:G	W506R	1.000

dbSNP variants (sampled 300 via entrez): RS1000044117 (15:82678800 T>G), RS1000179010 (15:82701211 G>C), RS1000179549 (15:82688934 G>A,T), RS1000267115 (15:82685664 C>G,T), RS1000425343 (15:82700743 G>A,C), RS1000465731 (15:82692360 G>A,C,T), RS1000540419 (15:82711827 G>A), RS1000566893 (15:82683595 T>C), RS1000597901 (15:82683965 A>G), RS1000671770 (15:82676933 A>G), RS1000808903 (15:82706540 A>AT), RS1000841395 (15:82693181 T>C), RS1000880016 (15:82683403 A>G), RS1000937437 (15:82696951 C>G), RS1000971001 (15:82670715 A>C,G)

Disease associations

OMIM: gene MIM:602166 | disease phenotypes: MIM:617276, MIM:612527, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 48	Strong	Autosomal recessive
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
genetic developmental and epileptic encephalopathy	Definitive	AR

Mondo (7): developmental and epileptic encephalopathy, 48 (MONDO:0015000), breast ductal adenocarcinoma (MONDO:0005590), Diamond-Blackfan anemia 4 (MONDO:0012924), intellectual disability (MONDO:0001071), microcephaly (MONDO:0001149), autism (MONDO:0005260), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (2): Diamond-Blackfan anemia (Orphanet:124), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

66 total (30 of 66 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000348	High forehead
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000510	Rod-cone dystrophy
HP:0000520	Proptosis
HP:0000527	Long eyelashes
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000637	Long palpebral fissure
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000750	Delayed speech and language development
HP:0000817	Reduced eye contact
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration
HP:0001272	Cerebellar atrophy
HP:0001273	Abnormal corpus callosum morphology
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001726_1	Lipoprotein-associated phospholipase A2 activity change in response to statin therapy	1.000000e-06
GCST004946_69	Schizophrenia	3.000000e-08
GCST007277_21	Tourette syndrome	7.000000e-06
GCST012226_373	Waist circumference adjusted for body mass index	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C567281	Diamond-Blackfan Anemia 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2
aristolochic acid I	increases expression	1
bisphenol A	affects cotreatment, decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects expression	1
manganese chloride	increases expression	1
entinostat	decreases expression	1
abrine	increases expression	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
Amphotericin B	increases expression	1
Cisplatin	decreases expression, affects cotreatment	1
Dexamethasone	decreases expression, affects cotreatment	1
Diazinon	increases methylation	1
Indomethacin	affects cotreatment, decreases expression	1
Manganese	increases expression	1
Oxygen	increases expression	1
Phthalic Acids	increases methylation	1
Testosterone	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Magnetite Nanoparticles	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism