AP1S3

adaptor related protein complex 1 subunit sigma 3, the group of Adaptor related protein complex 1

Basic information

Region (hg38): 2:223667679-223838027

Links

ENSG00000152056 ∙ NCBI:130340 ∙ OMIM:615781 ∙ HGNC:18971 ∙ Uniprot:Q96PC3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pustulosis palmaris et plantaris (Supportive), mode of inheritance: AD
• psoriasis 14, pustular (Supportive), mode of inheritance: AR
• psoriasis 14, pustular (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Psoriasis 15, pustular, susceptibility to	AD	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	Allergy/Immunology/Infectious; Dermatologic	24791904

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AP1S3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AP1S3 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				3		3
missense			2	4	2	8
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding				1	9	10
Total	0	0	3	8	11

Variants in AP1S3

This is a list of pathogenic ClinVar variants found in the AP1S3 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-223752845-T-C			Likely benign (Feb 01, 2023)
2-223765134-C-CT		not specified	Benign (Nov 12, 2023)
2-223765156-A-ACACCAT		not specified	Benign (Jan 24, 2024)
2-223765159-C-CCAT		not specified	Benign (Nov 12, 2023)
2-223765159-C-CCATCAT		not specified	Benign (Nov 12, 2023)
2-223765305-T-G		not specified	Uncertain significance (Jun 24, 2022)
2-223773250-A-G		not specified	Benign (Nov 12, 2023)
2-223775925-C-T		AP1S3-related disorder	Likely benign (Jun 14, 2019)
2-223775944-A-G		Psoriasis 15, pustular, susceptibility to	Benign (Aug 27, 2020)
2-223775952-C-T		AP1S3-related disorder	Likely benign (Mar 13, 2020)
2-223775957-A-C		AP1S3-related disorder	Benign (Jun 10, 2019)
2-223776002-T-C		not specified	Uncertain significance (Jan 30, 2024)
2-223776086-C-CAA		not specified	Benign (Nov 12, 2023)
2-223776146-C-T		not specified	Benign (Nov 12, 2023)
2-223776179-T-C		not specified	Benign (Jan 24, 2024)
2-223777776-G-A		Psoriasis 15, pustular, susceptibility to • not specified • AP1S3-related disorder	Benign/Likely benign (Jul 01, 2024)
2-223777778-G-A			Likely benign (Jul 01, 2024)
2-223777809-T-C		Psoriasis 15, pustular, susceptibility to • AP1S3-related disorder	Likely benign (Mar 01, 2024)
2-223777845-G-A			Uncertain significance (Jun 23, 2022)
2-223777862-A-C		Psoriasis 15, pustular, susceptibility to • AP1S3-related disorder	Benign/Likely benign (Jul 01, 2024)
2-223777875-AC-A		AP1S3-related disorder	Likely benign (Nov 18, 2019)
2-223837439-C-G		AP1S3-related disorder	Likely benign (Jul 15, 2019)
2-223837440-G-T		AP1S3-related disorder	Likely benign (Dec 18, 2019)
2-223837588-G-C		not specified	Benign (Jan 24, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AP1S3	protein_coding	protein_coding	ENST00000396654	5	86342

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0163	0.894	124762	0	14	124776	0.0000561

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.507	70	83.0	0.843	0.00000446	1021
Missense in Polyphen		35	39.853	0.87823		453
Synonymous	1.31	19	27.8	0.685	0.00000138	260
Loss of Function	1.43	4	8.48	0.472	4.20e-7	110

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000444	0.0000441
Middle Eastern	0.00	0.00
South Asian	0.0000984	0.0000980
Other	0.000333	0.000330

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Subunit of clathrin-associated adaptor protein complex 1 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. Involved in TLR3 trafficking (PubMed:24791904). {ECO:0000269|PubMed:24791904}.
• Pathway: Lysosome - Homo sapiens (human);Golgi Associated Vesicle Biogenesis;Lysosome Vesicle Biogenesis;Clathrin derived vesicle budding;Disease;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;Membrane Trafficking;Host Interactions of HIV factors;HIV Infection;MHC class II antigen presentation;Infectious disease;Immune System;Adaptive Immune System;Nef mediated downregulation of MHC class I complex cell surface expression;Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters;The role of Nef in HIV-1 replication and disease pathogenesis (Consensus)

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.438
• rvis_EVS: 1.3
• rvis_percentile_EVS: 93.94

Haploinsufficiency Scores

• pHI: 0.145
• hipred: Y
• hipred_score: 0.628

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.533

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ap1s3

Gene ontology

• Biological process: protein targeting;vesicle-mediated transport;antigen processing and presentation of exogenous peptide antigen via MHC class II;regulation of defense response to virus by virus
• Cellular component: Golgi membrane;lysosomal membrane;cytosol;clathrin-coated pit;membrane coat;cytoplasmic vesicle membrane;trans-Golgi network membrane;intracellular membrane-bounded organelle
• Molecular function: protein binding