AP5Z1

Chr 7AR

adaptor related protein complex 5 subunit zeta 1

Also known as: KIAA0415, SPG48, zeta

The protein functions as a putative helicase required for homologous recombination DNA double-strand break repair and may also be involved in endosomal transport as part of the AP-5 adaptor protein complex. Mutations cause spastic paraplegia 48, an autosomal recessive disorder affecting the motor system. The gene shows tolerance to loss-of-function variants (LOEUF 1.47), suggesting that complete loss of function may be required for disease manifestation.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 1.471 OMIM phenotype
Clinical SummaryAP5Z1
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Gene-Disease Validity (ClinGen)
hereditary spastic paraplegia · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
60 unique Pathogenic / Likely Pathogenic· 339 VUS of 800 total submissions
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GeneReview available — AP5Z1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.47LOEUF
pLI 0.000
Z-score -0.79
OE 1.14 (0.891.47)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.97Z-score
OE missense 1.37 (1.291.46)
700 obs / 511.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.14 (0.891.47)
00.351.4
Missense OE1.37 (1.291.46)
00.61.4
Synonymous OE1.61
01.21.6
LoF obs/exp: 43 / 37.7Missense obs/exp: 700 / 511.2Syn Z: -7.62

ClinVar Variant Classifications

800 submitted variants in ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic36
VUS339
Likely Benign272
Benign65
Conflicting47
24
Pathogenic
36
Likely Pathogenic
339
VUS
272
Likely Benign
65
Benign
47
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
18
0
6
0
24
Likely Pathogenic
30
2
3
1
36
VUS
5
280
47
7
339
Likely Benign
0
5
115
152
272
Benign
0
0
62
3
65
Conflicting
47
Total53287233163783

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

AP5Z1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC