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): 5:78000521-78294762

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 (Strong), mode of inheritance: AR
• Hermansky-Pudlak syndrome 2 (Supportive), mode of inheritance: AR
• Hermansky-Pudlak syndrome 2 (Definitive), 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 (601 variants)
• not provided (94 variants)
• not specified (57 variants)
• Autoinflammatory syndrome (37 variants)
• Inborn genetic diseases (33 variants)
• Hermansky-Pudlak syndrome (22 variants)
• AP3B1-related condition (2 variants)
• Thrombocytopenia;Abnormal bleeding (1 variants)
• Malignant tumor of prostate (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.

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			7	93	1	101
missense			313	3	2	318
nonsense	5	4	1			10
start loss						0
frameshift	14	12	1			27
inframe indel			3	2		5
splice donor/acceptor (+/-2bp)	1	9	2			12
splice region			17	22	3	42
non coding			19	79	43	141
Total	20	25	346	177	46

Highest pathogenic variant AF is 0.0000198

Variants in AP3B1

This is a list of pathogenic ClinVar variants found in the AP3B1 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-78002314-T-C		Hermansky-Pudlak syndrome	Likely benign (Jun 14, 2016)
5-78002342-GTTTA-G		Hermansky-Pudlak syndrome	Uncertain significance (Jun 14, 2016)
5-78002395-C-T		Hermansky-Pudlak syndrome 2	Uncertain significance (Jan 12, 2018)
5-78002420-G-A		Hermansky-Pudlak syndrome 2	Uncertain significance (Jan 12, 2018)
5-78002455-G-A		Hermansky-Pudlak syndrome 2	Uncertain significance (Jan 13, 2018)
5-78002522-C-G		Hermansky-Pudlak syndrome 2	Uncertain significance (Jan 13, 2018)
5-78002522-C-T		Hermansky-Pudlak syndrome 2	Uncertain significance (Jan 13, 2018)
5-78002523-T-C		Hermansky-Pudlak syndrome 2	Benign (Jan 13, 2018)
5-78002711-G-C		Hermansky-Pudlak syndrome 2	Uncertain significance (Jan 13, 2018)
5-78002761-A-G		Hermansky-Pudlak syndrome 2	Uncertain significance (Jan 12, 2018)
5-78002795-A-T		Hermansky-Pudlak syndrome • not specified	Benign (Nov 12, 2023)
5-78002801-A-G		Hermansky-Pudlak syndrome 2	Uncertain significance (Jan 13, 2018)
5-78002832-G-GA		Hermansky-Pudlak syndrome	Uncertain significance (Jun 14, 2016)
5-78002858-C-T		Hermansky-Pudlak syndrome 2	Benign (Jan 13, 2018)
5-78002861-T-C			Likely benign (Nov 10, 2018)
5-78002901-G-T		AP3B1-related disorder	Likely benign (Feb 09, 2021)
5-78002905-C-T		Hermansky-Pudlak syndrome 2	Likely benign (Nov 15, 2023)
5-78002922-G-C		Hermansky-Pudlak syndrome 2	Uncertain significance (Mar 25, 2020)
5-78002923-C-T		Hermansky-Pudlak syndrome 2	Likely benign (Aug 02, 2023)
5-78002933-C-T		Hermansky-Pudlak syndrome 2	Uncertain significance (Jan 28, 2022)
5-78002950-A-T		Hermansky-Pudlak syndrome 2	Likely benign (Feb 06, 2020)
5-78002957-G-A		Hermansky-Pudlak syndrome 2 • Autoinflammatory syndrome	Uncertain significance (Jan 18, 2024)
5-78002961-T-C		Hermansky-Pudlak syndrome 2	Uncertain significance (Jan 03, 2022)
5-78002973-T-C		Hermansky-Pudlak syndrome 2	Uncertain significance (Jul 21, 2023)
5-78002980-C-T		Hermansky-Pudlak syndrome 2	Conflicting classifications of pathogenicity (Jan 22, 2024)

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
0.615	0.385	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

Haploinsufficiency Scores

• pHI: 0.353
• hipred: Y
• hipred_score: 0.544
• ghis: 0.493

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

Mouse Genome Informatics

• Gene name: Ap3b1
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; pigmentation phenotype; limbs/digits/tail phenotype; 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); vision/eye phenotype; immune system phenotype

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