ZFYVE26

Chr 14AR

zinc finger FYVE-type containing 26

Also known as: FYVE-CENT, SPG15

NCBI Gene: 23503ENSG00000072121UniProt: Q68DK2

This gene encodes a protein which contains a FYVE zinc finger binding domain. The presence of this domain is thought to target these proteins to membrane lipids through interaction with phospholipids in the membrane. Mutations in this gene are associated with autosomal recessive spastic paraplegia-15. [provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

Spastic paraplegia 15, autosomal recessiveMIM #270700
AR
572
ClinVar variants
151
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ZFYVE26
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
151 Pathogenic / Likely Pathogenic· 296 VUS of 572 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.60LOEUF
pLI 0.000
Z-score 5.23
OE 0.48 (0.39–0.60)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.52Z-score
OE missense 0.96 (0.92–1.00)
1280 obs / 1333.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.48 (0.39–0.60)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.92–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 58 / 119.8Missense obs/exp: 1280 / 1333.4Syn Z: 0.51

ClinVar Variant Classifications

572 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic72
Likely Pathogenic79
VUS296
Likely Benign116
Benign3
Conflicting6
72
Pathogenic
79
Likely Pathogenic
296
VUS
116
Likely Benign
3
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
33
1
38
0
72
Likely Pathogenic
61
4
14
0
79
VUS
2
263
31
0
296
Likely Benign
0
1
42
73
116
Benign
0
0
3
0
3
Conflicting
—6
Total9626912873572

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

View in ClinVar →

Protein Context — Lollipop Plot

ZFYVE26 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ZFYVE26-related spastic paraplegia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spastic paraplegia 15, autosomal recessive

MIM #270700

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ZFYVE26
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy.
Deneubourg C et al.·Autophagy
2022
The clinical and molecular spectrum of ZFYVE26-associated hereditary spastic paraplegia: SPG15.
Saffari A et al.·Brain
2023
Investigating ZFYVE26 mutations in a Taiwanese cohort with hereditary spastic paraplegia.
Hsu SL et al.·J Formos Med Assoc
2022Cohort
A case of spastic paraplegia-15 with a novel pathogenic variant in ZFYVE26 gene.
Özdemir TR et al.·Int J Neurosci
2019Case report
Rare novel CYP2U1 and ZFYVE26 variants identified in two Pakistani families with spastic paraplegia.
Bibi F et al.·J Neurol Sci
2020Case report
Genetic Investigation of Consanguineous Pakistani Families Segregating Rare Spinocerebellar Disorders.
Saadi SM et al.·Genes (Basel)
2023
A hereditary spastic paraplegia mouse model supports a role of ZFYVE26/SPASTIZIN for the endolysosomal system.
Khundadze M et al.·PLoS Genet
2013Functional
Spastic paraplegia with thinning of the corpus callosum and white matter abnormalities: further mutations and relative frequency in ZFYVE26/SPG15 in the Italian population.
Denora PS et al.·J Neurol Sci
2009Case report
Molecular analysis and clinical diversity of distal hereditary motor neuropathy.
Liu X et al.·Eur J Neurol
2020
Genetic, clinical and neuroimaging profiles of sporadic and autosomal recessive hereditary spastic paraplegia cases in Chinese.
Dong Y et al.·Neurosci Lett
2021Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools