AP4S1
Basic information
Region (hg38): 14:31025106-31130996
Links
Phenotypes
GenCC
Source:
- 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:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Spastic paraplegia 52, autosomal recessive | AR | 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; Neurologic | 21620353 |
ClinVar
This is a list of variants' phenotypes submitted to
- 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.
Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 11 | 11 | ||||
missense | 30 | 33 | ||||
nonsense | 5 | |||||
start loss | 1 | 1 | ||||
frameshift | 7 | |||||
splice donor/acceptor (+/-2bp) | 8 | |||||
Total | 10 | 12 | 30 | 12 | 1 |
Highest pathogenic variant AF is 0.00187023
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
AP4S1 | protein_coding | protein_coding | ENST00000216366 | 5 | 68507 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.00000173 | 0.257 | 125679 | 0 | 56 | 125735 | 0.000223 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | -0.0101 | 85 | 84.7 | 1.00 | 0.00000423 | 1054 |
Missense in Polyphen | 24 | 24.6 | 0.9756 | 321 | ||
Synonymous | -0.390 | 30 | 27.4 | 1.09 | 0.00000119 | 286 |
Loss of Function | 0.119 | 9 | 9.39 | 0.958 | 6.17e-7 | 93 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000437 | 0.000437 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.000163 | 0.000163 |
Finnish | 0.0000462 | 0.0000462 |
European (Non-Finnish) | 0.000255 | 0.000255 |
Middle Eastern | 0.000163 | 0.000163 |
South Asian | 0.000229 | 0.000229 |
Other | 0.000326 | 0.000326 |
dbNSFP
Source:
- 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
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
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