AP1S2

adaptor related protein complex 1 subunit sigma 2, the group of Adaptor related protein complex 1

Basic information

Region (hg38): X:15825805-15854931

Previous symbols: [ "MRX59", "MRXS5", "PGS" ]

Links

ENSG00000182287 ∙ NCBI:8905 ∙ OMIM:300629 ∙ HGNC:560 ∙ Uniprot:P56377 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic X-linked intellectual disability 5 (Strong), mode of inheritance: XL
• syndromic X-linked intellectual disability 5 (Moderate), mode of inheritance: XL
• syndromic X-linked intellectual disability 5 (Definitive), mode of inheritance: XLR
• syndromic X-linked intellectual disability 5 (Supportive), mode of inheritance: XL
• fried syndrome (Supportive), mode of inheritance: XL
• autism spectrum disorder (Limited), mode of inheritance: XL
• syndromic X-linked intellectual disability 5 (Strong), mode of inheritance: XL
• X-linked syndromic intellectual disability (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pettigrew syndrome	XL	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	Craniofacial; Musculoskeletal; Neurologic	5054319; 10398241; 12599187; 17617514; 18428203; 19377476; 2018058; 22210230; 23756445

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AP1S2 gene.

• not provided (40 variants)
• Pettigrew syndrome (10 variants)
• Inborn genetic diseases (6 variants)
• not specified (5 variants)
• Pettigrew syndrome;Fried syndrome (1 variants)
• AP1S2-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AP1S2 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			1	6	1	8
missense			8	1		9
nonsense	3					3
start loss						0
frameshift	3	2				5
inframe indel			1			1
splice donor/acceptor (+/-2bp)	3	1				4
splice region	1	1	1	3		6
non coding	2		2	5	9	18
Total	11	3	12	12	10

Variants in AP1S2

This is a list of pathogenic ClinVar variants found in the AP1S2 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-15827084-T-G		Pettigrew syndrome	Uncertain significance (May 02, 2023)
X-15827324-G-A		Inborn genetic diseases	Uncertain significance (Jan 26, 2017)
X-15827326-T-C			Likely benign (Jul 25, 2023)
X-15827328-T-C			Likely benign (Nov 19, 2021)
X-15827335-C-T			Uncertain significance (Jul 11, 2022)
X-15827336-C-T			Uncertain significance (Apr 07, 2020)
X-15827377-G-A		not specified	Likely benign (Sep 29, 2017)
X-15827389-TGA-T			Likely benign (Mar 15, 2021)
X-15828209-G-T		not specified	Likely benign (Sep 16, 2015)
X-15845153-T-C			Benign (May 10, 2021)
X-15845173-T-C			Benign (May 10, 2021)
X-15845186-A-G			Benign (May 10, 2021)
X-15845364-G-C			Likely benign (Jun 29, 2023)
X-15845378-C-A		Pettigrew syndrome	Pathogenic (Sep 26, 2013)
X-15845389-A-C			Uncertain significance (Jan 22, 2024)
X-15845419-T-A			Uncertain significance (Aug 22, 2022)
X-15845438-G-A			Pathogenic (Mar 31, 2023)
X-15845470-ATAAAATAAGCCTTC-A		Pettigrew syndrome	Likely pathogenic (Jun 04, 2020)
X-15845496-G-A			Likely benign (Aug 21, 2022)
X-15845518-T-C			Pathogenic (Apr 21, 2016)
X-15845524-G-A		not specified • Inborn genetic diseases • AP1S2-related disorder	Benign/Likely benign (Nov 14, 2023)
X-15845525-G-A			Likely benign (Dec 09, 2017)
X-15845525-GA-G			Benign (Nov 23, 2023)
X-15845525-G-GA			Benign (Oct 24, 2023)
X-15845830-A-T			Benign (May 10, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AP1S2	protein_coding	protein_coding	ENST00000329235	4	29126

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.867	0.131	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.01	15	58.2	0.258	0.00000455	1027
Missense in Polyphen		5	18.951	0.26384		361
Synonymous	-0.425	22	19.6	1.12	0.00000137	286
Loss of Function	2.38	0	6.60	0.00	5.37e-7	112

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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.
• 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: 0.0507

Intolerance Scores

• rvis_EVS: 0.06
• rvis_percentile_EVS: 58

Haploinsufficiency Scores

• pHI: 0.749
• hipred: Y
• hipred_score: 0.809
• ghis: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.846

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Ap1s2
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); 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); cellular 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: intracellular protein transport;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;Golgi apparatus;cytosol;clathrin-coated pit;AP-type membrane coat adaptor complex;cytoplasmic vesicle membrane;trans-Golgi network membrane;intracellular membrane-bounded organelle
• Molecular function: protein binding