AP5Z1
Basic information
Region (hg38): 7:4775614-4794397
Previous symbols: [ "KIAA0415" ]
Links
Phenotypes
GenCC
Source:
- hereditary spastic paraplegia 48 (Moderate), mode of inheritance: AR
- hereditary spastic paraplegia 48 (Moderate), mode of inheritance: AR
- hereditary spastic paraplegia 48 (Strong), mode of inheritance: AR
- hereditary spastic paraplegia 48 (Supportive), mode of inheritance: AR
- hereditary spastic paraplegia (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Spastic paraplegia 48, 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 | Neurologic | 20613862; 22554690 |
ClinVar
This is a list of variants' phenotypes submitted to
- Hereditary spastic paraplegia 48 (763 variants)
- not provided (275 variants)
- Hereditary spastic paraplegia (107 variants)
- Inborn genetic diseases (82 variants)
- not specified (38 variants)
- Spastic Paraplegia, Recessive (4 variants)
- AP5Z1-related condition (1 variants)
- High myopia (1 variants)
- Spastic paraplegia (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the AP5Z1 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 | 13 | 140 | 11 | 164 | ||
| missense | 312 | 322 | ||||
| nonsense | 15 | |||||
| start loss | 0 | |||||
| frameshift | 16 | |||||
| inframe indel | 11 | |||||
| splice donor/acceptor (+/-2bp) | 9 | |||||
| splice region ? | 1 | 17 | 21 | 3 | 42 | |
| non coding ? | 121 | 122 | 72 | 315 | ||
| Total | 16 | 19 | 460 | 271 | 86 |
Highest pathogenic variant AF is 0.0000920
Variants in AP5Z1
This is a list of pathogenic ClinVar variants found in the AP5Z1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| AP5Z1 | protein_coding | protein_coding | ENST00000348624 | 17 | 18691 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 7.29e-31 | 0.00000603 | 124560 | 0 | 185 | 124745 | 0.000742 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -2.97 | 700 | 511 | 1.37 | 0.0000354 | 5064 |
| Missense in Polyphen | 197 | 132.74 | 1.4841 | 1313 | ||
| Synonymous | -7.62 | 407 | 253 | 1.61 | 0.0000191 | 1758 |
| Loss of Function | -0.793 | 43 | 37.7 | 1.14 | 0.00000216 | 375 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00146 | 0.00144 |
| Ashkenazi Jewish | 0.000714 | 0.000696 |
| East Asian | 0.000914 | 0.000890 |
| Finnish | 0.000444 | 0.000418 |
| European (Non-Finnish) | 0.000949 | 0.000920 |
| Middle Eastern | 0.000914 | 0.000890 |
| South Asian | 0.000626 | 0.000588 |
| Other | 0.000170 | 0.000165 |
dbNSFP
Source:
- Function
- FUNCTION: As part of AP-5, a probable fifth adaptor protein complex it may be involved in endosomal transport. According to PubMed:20613862 it is a putative helicase required for efficient homologous recombination DNA double-strand break repair. {ECO:0000269|PubMed:20613862, ECO:0000269|PubMed:22022230}.;
- Disease
- DISEASE: Spastic paraplegia 48, autosomal recessive (SPG48) [MIM:613647]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. {ECO:0000269|PubMed:20613862}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.102
Intolerance Scores
- loftool
- rvis_EVS
- -0.6
- rvis_percentile_EVS
- 17.52
Haploinsufficiency Scores
- pHI
- 0.135
- hipred
- hipred_score
- ghis
- 0.506
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ap5z1
- Phenotype
Gene ontology
- Biological process
- double-strand break repair via homologous recombination;protein transport;endosomal transport
- Cellular component
- nucleus;nucleoplasm;cytoplasm;nuclear speck;AP-type membrane coat adaptor complex;AP-5 adaptor complex
- Molecular function
- protein binding