AP3B1

adaptor related protein complex 3 subunit beta 1, the group of Clathrin/coatomer adaptor, adaptin-like, N-terminal domain containing|Adaptor related protein complex 3

Basic information

Region (hg38): 5:77991640-78294762

Links

ENSG00000132842 ∙ NCBI:8546 ∙ OMIM:603401 ∙ HGNC:566 ∙ Uniprot:O00203 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Hermansky-Pudlak syndrome 2 (Definitive), mode of inheritance: AR
• Hermansky-Pudlak syndrome 2 (Strong), mode of inheritance: AR
• Hermansky-Pudlak syndrome 2 (Supportive), mode of inheritance: AR
• Hermansky-Pudlak syndrome 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hermansky-Pudlak syndrome 2	AR	Allergy/Immunology/Infectious; Dermatologic; Hematologic; Pulmonary	Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Prompt treatment of pulmonary infections (as well as avoidance of cigarette smoke) to maximize pulmonary function is indicated, including influenza and pneumococcus vaccination	Allergy/Immunology/Infectious; Dental; Dermatologic; Hematologic; Neurologic; Ophthalmologic; Pulmonary	10024875; 11809908; 16507770; 16537806; 20301464; 23215637

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AP3B1 gene.

• Hermansky-Pudlak_syndrome_2 (806 variants)
• Inborn_genetic_diseases (121 variants)
• not_provided (104 variants)
• not_specified (80 variants)
• Autoinflammatory_syndrome (36 variants)
• AP3B1-related_disorder (24 variants)
• Hermansky-Pudlak_syndrome (12 variants)
• Thrombocytopenia (1 variants)
• Prostate_cancer (1 variants)
• Combined_immunodeficiency (1 variants)
• Abnormal_bleeding (1 variants)
• Intellectual_disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AP3B1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003664.5. 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			7	188	3	198
missense	2	1	406	15	5	429
nonsense	12	4	1			17
start loss						0
frameshift	22	14	2			38
splice donor/acceptor (+/-2bp)	5	14	10			29
Total	41	33	426	203	8

Highest pathogenic variant AF is 0.000018474726

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AP3B1	protein_coding	protein_coding	ENST00000255194	27	294231

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125715	0	33	125748	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.890	508	568	0.895	0.0000277	7198
Missense in Polyphen		81	122.78	0.65969		1523
Synonymous	1.37	172	197	0.875	0.00000975	2073
Loss of Function	5.63	13	60.1	0.216	0.00000312	742

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000364	0.000360
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000140	0.000139
European (Non-Finnish)	0.000133	0.000132
Middle Eastern	0.00	0.00
South Asian	0.000229	0.000163
Other	0.000163	0.000163

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: Hermansky-Pudlak syndrome 2 (HPS2) [MIM:608233]: A form of Hermansky-Pudlak syndrome, a genetically heterogeneous autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS. HPS2 differs from the other forms of HPS in that it includes immunodeficiency in its phenotype and patients with HPS2 have an increased susceptibility to infections. {ECO:0000269|PubMed:10024875}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Golgi Associated Vesicle Biogenesis;Clathrin derived vesicle budding;Disease;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;Membrane Trafficking;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction (Consensus)

Recessive Scores

• pRec: 0.316

Intolerance Scores

• loftool: 0.483
• rvis_EVS: 0.43
• rvis_percentile_EVS: 77.29

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.824

Gene Damage Prediction

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

Gene ontology

• Biological process: protein targeting to lysosome;intracellular protein transport;blood coagulation;anterograde axonal transport;synaptic vesicle budding from endosome;melanosome organization;antigen processing and presentation, exogenous lipid antigen via MHC class Ib;anterograde synaptic vesicle transport;positive regulation of NK T cell differentiation
• Cellular component: lysosomal membrane;Golgi apparatus;membrane;AP-3 adaptor complex;clathrin adaptor complex;clathrin-coated vesicle membrane;postsynapse;axon cytoplasm
• Molecular function: protein phosphatase binding;GTP-dependent protein binding