AP3D1

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

Basic information

Region (hg38): 19:2100988-2164468

Links

ENSG00000065000 ∙ NCBI:8943 ∙ OMIM:607246 ∙ HGNC:568 ∙ Uniprot:O14617 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Hermansky-Pudlak syndrome 10 (Moderate), mode of inheritance: AR
• Hermansky-Pudlak syndrome 10 (Limited), mode of inheritance: Unknown
• Hermansky-Pudlak syndrome 10 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hermansky-Pudlak syndrome 10	AR	Allergy/Immunology/Infectious	The condition can involve neutropenia and susceptibility to infections, and prompt and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Neurologic; Ophthalmologic	26744459

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AP3D1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AP3D1 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			6	273	12	291
missense			400	11	2	413
nonsense						0
start loss						0
frameshift		1	2			3
inframe indel			13	1		14
splice donor/acceptor (+/-2bp)			5			5
splice region			41	50	7	98
non coding			7	215	92	314
Total	0	1	433	500	106

Variants in AP3D1

This is a list of pathogenic ClinVar variants found in the AP3D1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-2102028-G-A			Likely benign (May 16, 2021)
19-2102181-T-C		Inborn genetic diseases	Uncertain significance (Dec 30, 2023)
19-2102184-C-T		Hermansky-Pudlak syndrome 10 • AP3D1-related disorder	Uncertain significance (Jan 03, 2024)
19-2102187-G-A			Likely benign (Dec 20, 2022)
19-2102188-C-T			Likely benign (Dec 11, 2023)
19-2102189-G-A			Uncertain significance (Aug 18, 2023)
19-2102192-G-A			Uncertain significance (Oct 24, 2023)
19-2102194-C-T			Likely benign (Nov 03, 2023)
19-2102199-T-C			Uncertain significance (Dec 28, 2023)
19-2102200-C-T			Likely benign (Mar 12, 2022)
19-2102205-C-T			Uncertain significance (Nov 28, 2023)
19-2102206-T-C		AP3D1-related disorder	Likely benign (Jan 08, 2024)
19-2102216-C-G			Uncertain significance (Oct 27, 2020)
19-2102224-C-T		AP3D1-related disorder	Likely benign (Nov 15, 2022)
19-2102225-G-A		not specified • Inborn genetic diseases	Uncertain significance (Jan 18, 2024)
19-2102245-G-A			Likely benign (May 14, 2022)
19-2102247-C-T			Uncertain significance (Nov 27, 2023)
19-2102248-G-A			Likely benign (Sep 27, 2022)
19-2102254-GAC-G		Hermansky-Pudlak syndrome 10	Pathogenic (Jul 27, 2016)
19-2102258-G-C			Uncertain significance (Jan 13, 2023)
19-2102277-G-C			Likely benign (Feb 07, 2023)
19-2102280-A-G			Likely benign (Feb 22, 2023)
19-2102287-T-C			Likely benign (Jan 06, 2024)
19-2102511-C-G			Benign (Dec 24, 2018)
19-2102544-G-C			Benign (Dec 24, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AP3D1	protein_coding	protein_coding	ENST00000355272	32	63477

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.986	0.0135	124822	0	23	124845	0.0000921

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.94	603	753	0.801	0.0000483	7960
Missense in Polyphen		98	202.08	0.48496		2081
Synonymous	-2.24	384	332	1.16	0.0000250	2283
Loss of Function	5.97	11	61.5	0.179	0.00000279	759

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000485	0.000479
Ashkenazi Jewish	0.000101	0.0000993
East Asian	0.00	0.00
Finnish	0.000140	0.000139
European (Non-Finnish)	0.0000746	0.0000706
Middle Eastern	0.00	0.00
South Asian	0.0000667	0.0000654
Other	0.000171	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated. The complex is associated with the Golgi region as well as more peripheral structures. It facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to lysosomes. Involved in process of CD8+ T-cell and NK cell degranulation (PubMed:26744459). 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 (By similarity). {ECO:0000250|UniProtKB:O54774, ECO:0000269|PubMed:26744459}.
• Pathway: Lysosome - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase (Consensus)

Recessive Scores

• pRec: 0.188

Intolerance Scores

• loftool: 0.225
• rvis_EVS: -2.28
• rvis_percentile_EVS: 1.24

Haploinsufficiency Scores

• pHI: 0.315
• hipred: Y
• hipred_score: 0.601
• ghis: 0.633

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.844

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ap3d1
• 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); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; vision/eye phenotype; reproductive system phenotype; 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); hematopoietic system phenotype; pigmentation phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system 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); hearing/vestibular/ear phenotype

Gene ontology

• Biological process: protein targeting to vacuole;eye pigment biosynthetic process;intracellular protein transport;Golgi to vacuole transport;anterograde axonal transport;synaptic vesicle budding from endosome;melanosome organization;endosome to melanosome transport;antigen processing and presentation, exogenous lipid antigen via MHC class Ib;anterograde synaptic vesicle transport;synaptic vesicle membrane organization;positive regulation of NK T cell differentiation;regulation of sequestering of zinc ion;protein localization to membrane;neurotransmitter receptor transport, postsynaptic endosome to lysosome
• Cellular component: Golgi membrane;lysosomal membrane;Golgi apparatus;plasma membrane;endosome membrane;membrane;AP-3 adaptor complex;terminal bouton;postsynapse;presynaptic endosome;glutamatergic synapse;axon cytoplasm
• Molecular function: transporter activity