AP1S1

adaptor related protein complex 1 subunit sigma 1, the group of Adaptor related protein complex 1|MicroRNA protein coding host genes

Basic information

Region (hg38): 7:101154456-101161596

Previous symbols: [ "CLAPS1", "EKV3" ]

Links

ENSG00000106367 ∙ NCBI:1174 ∙ OMIM:603531 ∙ HGNC:559 ∙ Uniprot:P61966 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• MEDNIK syndrome (Strong), mode of inheritance: AR
• MEDNIK syndrome (Strong), mode of inheritance: AR
• MEDNIK syndrome (Supportive), mode of inheritance: AR
• MEDNIK syndrome (Strong), mode of inheritance: AR
• MEDNIK syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
MEDNIK syndrome	AR	Audiologic/Otolaryngologic; Biochemical	As the condition may include hearing loss, recognition and interventions related to speech and language development may be beneficial; The condition involves abnormal copper metabolism, and medical management (with Zinc acetate) has been shown to be beneficial related to both lab-based as well as clinical outcomes	Audiologic/Otolaryngologic; Biochemical; Dermatologic; Neurologic	19057675; 23423674; 23622398; 24754424

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AP1S1 gene.

• not_provided (127 variants)
• Inborn_genetic_diseases (14 variants)
• MEDNIK_syndrome (9 variants)
• AP1S1-related_disorder (5 variants)
• not_specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AP1S1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001283.5. 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				48	5	53
missense			17	1		18
nonsense	2	2				4
start loss			1			1
frameshift		2				2
splice donor/acceptor (+/-2bp)	1	2	1			4
Total	3	6	19	49	5

Highest pathogenic variant AF is 0.0000427963

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AP1S1	protein_coding	protein_coding	ENST00000337619	5	7200

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.100	0.869	124545	0	3	124548	0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.74	41	86.7	0.473	0.00000495	1021
Missense in Polyphen		12	34.558	0.34725		424
Synonymous	0.401	33	36.1	0.915	0.00000213	277
Loss of Function	1.85	3	9.00	0.334	4.42e-7	107

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)	0.0000365	0.0000266
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. {ECO:0000269|PubMed:9733768}.
• Disease: DISEASE: Mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma (MEDNIK) [MIM:609313]: A disorder characterized by erythematous skin lesions and hyperkeratosis, severe psychomotor retardation, peripheral neuropathy, sensorineural hearing loss, together with elevated very-long-chain fatty acids and severe congenital diarrhea. {ECO:0000269|PubMed:19057675}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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: 0.138

Intolerance Scores

• loftool: 0.611
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.2

Haploinsufficiency Scores

• pHI: 0.281
• hipred: Y
• hipred_score: 0.645
• ghis: 0.601

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.931

Mouse Genome Informatics

• Gene name: Ap1s1

Zebrafish Information Network

• Gene name: ap1s1
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: intracellular protein transport;receptor-mediated endocytosis;response to virus;antigen processing and presentation of exogenous peptide antigen via MHC class II;retrograde transport, endosome to Golgi;regulation of defense response to virus by virus
• Cellular component: Golgi membrane;lysosomal membrane;Golgi apparatus;cytosol;clathrin-coated pit;membrane;AP-1 adaptor complex;cytoplasmic vesicle membrane;trans-Golgi network membrane;terminal bouton;intracellular membrane-bounded organelle