AP4S1

adaptor related protein complex 4 subunit sigma 1, the group of Adaptor related protein complex 4

Basic information

Region (hg38): 14:31025106-31130996

Links

ENSG00000100478NCBI:11154OMIM:607243HGNC:575Uniprot:Q9Y587AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • hereditary spastic paraplegia 52 (Strong), mode of inheritance: AR
  • hereditary spastic paraplegia 52 (Strong), mode of inheritance: AR
  • AP4-related intellectual disability and spastic paraplegia (Supportive), mode of inheritance: AR
  • AP-4 deficiency syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Spastic paraplegia 52, autosomal recessiveARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Neurologic21620353

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AP4S1 gene.

  • Spastic_paraplegia (76 variants)
  • not_provided (29 variants)
  • not_specified (26 variants)
  • Inborn_genetic_diseases (26 variants)
  • Hereditary_spastic_paraplegia_52 (19 variants)
  • Hereditary_spastic_paraplegia (6 variants)
  • AP4S1-related_disorder (4 variants)
  • Neurodevelopmental_disorder (2 variants)
  • Intellectual_disability (2 variants)
  • APS41-related_disorder (1 variants)
  • Spastic_Paraplegia_52 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AP4S1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001128126.3. 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.

EffectPLPVUSLBBSum
synonymous
11
clinvar
11
missense
1
clinvar
30
clinvar
1
clinvar
1
clinvar
33
nonsense
4
clinvar
1
clinvar
5
start loss
1
1
frameshift
4
clinvar
3
clinvar
7
splice donor/acceptor (+/-2bp)
2
clinvar
6
clinvar
8
Total 10 12 30 12 1

Highest pathogenic variant AF is 0.00187023

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
AP4S1protein_codingprotein_codingENST00000216366 568507
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.000001730.2571256790561257350.000223
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.01018584.71.000.000004231054
Missense in Polyphen2424.60.9756321
Synonymous-0.3903027.41.090.00000119286
Loss of Function0.11999.390.9586.17e-793

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004370.000437
Ashkenazi Jewish0.000.00
East Asian0.0001630.000163
Finnish0.00004620.0000462
European (Non-Finnish)0.0002550.000255
Middle Eastern0.0001630.000163
South Asian0.0002290.000229
Other0.0003260.000326

dbNSFP

Source: dbNSFP

Function
FUNCTION: Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (PubMed:10066790, PubMed:10436028). AP-4 forms a non clathrin- associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal (Probable). {ECO:0000269|PubMed:10066790, ECO:0000269|PubMed:10436028, ECO:0000305|PubMed:10066790, ECO:0000305|PubMed:10436028}.;
Pathway
Lysosome - Homo sapiens (human);Lysosome Vesicle Biogenesis;Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;Membrane Trafficking (Consensus)

Intolerance Scores

loftool
0.382
rvis_EVS
-0.36
rvis_percentile_EVS
28.63

Haploinsufficiency Scores

pHI
0.164
hipred
N
hipred_score
0.177
ghis
0.637

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.982

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Ap4s1
Phenotype

Gene ontology

Biological process
protein targeting;protein localization
Cellular component
AP-4 adaptor complex;endosome lumen;trans-Golgi network membrane;intracellular membrane-bounded organelle
Molecular function