AP3B2

adaptor related protein complex 3 subunit beta 2, the group of Clathrin/coatomer adaptor, adaptin-like, N-terminal domain containing|Adaptor related protein complex 3

Basic information

Region (hg38): 15:82659281-82710112

Links

ENSG00000103723 ∙ NCBI:8120 ∙ OMIM:602166 ∙ HGNC:567 ∙ Uniprot:Q13367 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 48 (Strong), mode of inheritance: AR
• developmental and epileptic encephalopathy, 48 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 48	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	27431290; 27431290

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AP3B2 gene.

• not_provided (786 variants)
• Inborn_genetic_diseases (120 variants)
• Developmental_and_epileptic_encephalopathy,_48 (45 variants)
• AP3B2-related_disorder (27 variants)
• not_specified (5 variants)
• Epileptic_encephalopathy (2 variants)
• Microcephaly (2 variants)
• Generalized_hypotonia (1 variants)
• Global_developmental_delay (1 variants)
• Abnormal_speech_pattern (1 variants)
• Intellectual_disability (1 variants)
• Gastroesophageal_reflux (1 variants)
• Delayed_speech_and_language_development (1 variants)
• EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
• Autism (1 variants)
• Feeding_difficulties (1 variants)
• Abnormality_of_eye_movement (1 variants)
• Hypotonia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AP3B2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001278512.2. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	3	250	4	258
missense	1		312	10	1	324
nonsense	10	5	1			16
start loss			1			1
frameshift	16	7	1			24
splice donor/acceptor (+/-2bp)	2	7	3			12
Total	29	20	321	260	5

Highest pathogenic variant AF is 0.0000123928

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AP3B2	protein_coding	protein_coding	ENST00000261722	26	50634

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.772	0.228	124621	0	29	124650	0.000116

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.92	413	617	0.669	0.0000342	6997
Missense in Polyphen		57	143.83	0.3963		1533
Synonymous	-0.146	253	250	1.01	0.0000142	2174
Loss of Function	5.37	11	53.3	0.206	0.00000262	631

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000465	0.000465
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000928	0.0000928
European (Non-Finnish)	0.000116	0.000115
Middle Eastern	0.00	0.00
South Asian	0.0000655	0.0000654
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: 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.
• Disease: DISEASE: Epileptic encephalopathy, early infantile, 48 (EIEE48) [MIM:617276]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood 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. EIEE48 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. {ECO:0000269|PubMed:27431290, ECO:0000269|PubMed:27889060}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.194

Intolerance Scores

• rvis_EVS: -1.62
• rvis_percentile_EVS: 2.93

Haploinsufficiency Scores

• pHI: 0.283
• hipred: Y
• hipred_score: 0.671
• ghis: 0.637

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.929

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ap3b2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: intracellular protein transport;post-Golgi vesicle-mediated transport;anterograde axonal transport;anterograde synaptic vesicle transport
• Cellular component: Golgi apparatus;AP-3 adaptor complex;COPI-coated vesicle;clathrin-coated vesicle membrane;axon cytoplasm
• Molecular function: transporter activity