AP5Z1

adaptor related protein complex 5 subunit zeta 1, the group of Armadillo like helical domain containing|Adaptor related protein complex 5

Basic information

Region (hg38): 7:4775615-4794397

Previous symbols: [ "KIAA0415" ]

Links

ENSG00000242802 ∙ NCBI:9907 ∙ OMIM:613653 ∙ HGNC:22197 ∙ Uniprot:O43299 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the AP5Z1 gene.

• Hereditary_spastic_paraplegia_48 (702 variants)
• not_provided (255 variants)
• Inborn_genetic_diseases (221 variants)
• Hereditary_spastic_paraplegia (92 variants)
• not_specified (43 variants)
• AP5Z1-related_disorder (25 variants)
• Retinal_dystrophy (22 variants)
• Macular_dystrophy_with_or_without_extraocular_features (16 variants)
• Optic_atrophy (3 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. These statistics are base on transcript: NM_000014855.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		2	13	228	9	252
missense		3	415	25	1	444
nonsense	9	12				21
start loss						0
frameshift	14	19	5			38
splice donor/acceptor (+/-2bp)	1	13			1	15
Total	24	49	433	253	11

Highest pathogenic variant AF is 0.000137829

GnomAD

Source: gnomAD

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: dbNSFP

• 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

• rvis_EVS: -0.6
• rvis_percentile_EVS: 17.52

Haploinsufficiency Scores

• pHI: 0.135
• 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

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