ZFYVE26

Chr 14AR

zinc finger FYVE-type containing 26

Also known as: FYVE-CENT, SPG15

The protein contains a FYVE zinc finger domain that targets it to membrane lipids through phospholipid interactions and localizes to the cytoplasm, cytoskeleton, and centrosome. Mutations cause autosomal recessive spastic paraplegia-15, a hereditary spastic paraplegia characterized by progressive lower limb spasticity and weakness. The pathogenic mechanism involves disruption of the protein's membrane targeting function and its role in centrosomal organization.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.601 OMIM phenotype
Clinical SummaryZFYVE26
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.60LOEUF
pLI 0.000
Z-score 5.23
OE 0.48 (0.390.60)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.52Z-score
OE missense 0.96 (0.921.00)
1280 obs / 1333.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.48 (0.390.60)
00.351.4
Missense OE0.96 (0.921.00)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 58 / 119.8Missense obs/exp: 1280 / 1333.4Syn Z: 0.51
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveZFYVE26-related spastic paraplegiaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6356th %ile
GOF
0.4480th %ile
LOF
0.3746th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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