EPG5

Chr 18AR

ectopic P-granules 5 autophagy tethering factor

Also known as: HEEW1, KIAA1632, NEDPAM, VICIS

NCBI Gene: 57724ENSG00000152223UniProt: Q9HCE0

This gene encodes a large coiled coil domain-containing protein that functions in autophagy during starvation conditions. Mutations in this gene cause Vici syndrome. [provided by RefSeq, Aug 2015]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with parkinsonism or other movement abnormalitiesMIM #621506
Vici syndromeMIM #242840
AR
600
ClinVar variants
74
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— EPG5
🧬
Gene-Disease Validity (ClinGen)
Vici syndrome · 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
74 Pathogenic / Likely Pathogenic· 233 VUS of 600 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.46LOEUF
pLI 0.000
Z-score 6.88
OE 0.36 (0.28–0.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.08Z-score
OE missense 0.92 (0.87–0.96)
1233 obs / 1344.4 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.0.36 (0.28–0.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.87–0.96)
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.1.05
0≤1.21.6
LoF obs/exp: 48 / 134.0Missense obs/exp: 1233 / 1344.4Syn Z: -0.95

ClinVar Variant Classifications

600 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic21
VUS233
Likely Benign290
Benign3
53
Pathogenic
21
Likely Pathogenic
233
VUS
290
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
2
36
0
53
Likely Pathogenic
11
1
8
1
21
VUS
0
222
10
1
233
Likely Benign
0
5
103
182
290
Benign
0
1
2
0
3
Total26231159184600

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

View in ClinVar →

Protein Context — Lollipop Plot

EPG5 · protein map & ClinVar variants

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

Gene2Phenotype Curations

EPG5-related immunodeficiency, cardiomyopathy, cataract, hypopigmentation, and absent corpus callosum

definitive
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersEyeSkin
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with parkinsonism or other movement abnormalities

MIM #621506

Molecular basis of disorder known

Vici syndrome

MIM #242840

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — EPG5
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
An update on autophagy disorders.
Dafsari HS et al.·J Inherit Metab Dis
2025Review
Vici syndrome with pathogenic homozygous EPG5 gene mutation: A case report and literature review.
Abidi KT et al.·Medicine (Baltimore)
2020Review
Vici syndrome: a review.
Byrne S et al.·Orphanet J Rare Dis
2016Review
Epg5 links proteotoxic stress due to defective autophagic clearance and epileptogenesis in Drosophila and Vici syndrome patients.
Deneubourg C et al.·Autophagy
2025Cohort
First description of a patient with Vici syndrome due to a mutation affecting the penultimate exon of EPG5 and review of the literature.
Ehmke N et al.·Am J Med Genet A
2014Review
Expanding the Autosomal Recessive Gene Spectrum of Parkinson's Disease: A Study within the CPD10KGP.
Zhao Y et al.·Mov Disord
2025
The genetics of autosomal recessive early-onset Parkinson's disease.
Cogan G et al.·Curr Opin Neurobiol
2025Review
Exploring prognostic biomarkers in pathological images of colorectal cancer patients via deep learning.
Wei B et al.·J Pathol Clin Res
2024Cohort
Mutations in the Key Autophagy Tethering Factor EPG5 Link Neurodevelopmental and Neurodegenerative Disorders Including Early-Onset Parkinsonism.
Dafsari HS et al.·Ann Neurol
2025
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