VMP1

Chr 17

vacuole membrane protein 1

Also known as: EPG3, TANGO5, TMEM49

NCBI Gene: 81671UniProt: Q96GC9

This gene encodes a transmembrane protein that plays a key regulatory role in the process of autophagy. The ectopic overexpression of the encoded protein in cultured cells triggers autophagy even under nutrient-rich conditions. This gene is overexpressed in pancreatitis affected acinar cells where the encoded protein mediates sequestration and degradation of potentially deleterious activated zymogen granules in a process termed, zymophagy. [provided by RefSeq, Jul 2016]

0
Active trials
47
ClinVar variants
14
Pathogenic / LP
2.2
Missense Z
0.33
LOEUF· LoF intolerant
10
Pubs (2 yr)
Clinical Summary— VMP1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 31 VUS of 47 total submissions
Some data sources returned errors (1)

ensembl: Error: Ensembl fetch failed: 500 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/VMP1?content-type=application/json&expand=1

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.33LOEUF
pLI 0.963
Z-score 3.92
OE 0.13 (0.06–0.33)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
2.25Z-score
OE missense 0.57 (0.49–0.67)
126 obs / 219.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.13 (0.06–0.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.57 (0.49–0.67)
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.0.84
0≤1.21.6
LoF obs/exp: 3 / 23.5Missense obs/exp: 126 / 219.8Syn Z: 1.09

ClinVar Variant Classifications

47 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic2
VUS31
Likely Benign2
12
Pathogenic
2
Likely Pathogenic
31
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
2
0
2
VUS
1
26
4
0
31
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total12818047

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

View in ClinVar →

Protein Context — Lollipop Plot

VMP1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Panax ginseng extract prevents UVB-induced skin photodamage by modulating VMP1-mediated ER stress.
Chen J et al.·Phytomedicine
2024
Ubiquitination Is a Novel Post-Translational Modification of VMP1 in Autophagy of Human Tumor Cells.
Renna FJ et al.·Int J Mol Sci
2023
Downregulation of VMP1 confers aggressive properties to colorectal cancer.
Guo XZ et al.·Oncol Rep
2015
Relevance of miR-21 in HIV and non-HIV-related lymphomas.
Sekar D et al.·Tumour Biol
2014Review
Prognosis-related autophagy genes in female lung adenocarcinoma.
Liu Z et al.·Medicine (Baltimore)
2022
Genome-wide CRISPR screen identifies TMEM41B as a gene required for autophagosome formation.
Morita K et al.·J Cell Biol
2018
Novel roles of Vmp1: inhibition metastasis and proliferation of hepatocellular carcinoma.
Guo L et al.·Cancer Sci
2012
Comprehensive genomic profiling reveals a unique genomic landscape in solid tumors in an Indian cancer cohort of 1000 patients: a single institutional experience.
Ghosh M et al.·Sci Rep
2025Cohort
The pancreatitis-associated protein VMP1, a key regulator of inducible autophagy, promotes Kras(G12D)-mediated pancreatic cancer initiation.
Loncle C et al.·Cell Death Dis
2016
Genomic and transcriptomic characterisation of undifferentiated pleomorphic sarcoma of bone.
Ali NM et al.·J Pathol
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Loss of VMP1 Impairs Tight Junction Recycling and Aggravates Intestinal Barrier Dysfunction in Inflammatory Bowel Disease.
Zhao J et al.·Adv Sci (Weinh)
2026
Liraglutide Mitigates Renal Injury in Diabetic Kidney Disease by Suppressing Podocyte Cholesterol Accumulation Through mTOR/VMP1-Regulated Autophagy.
Zou Q et al.·FASEB J
2025
VMP1 enhances autophagy to mitigate cardiac fibroblast activation and reduce post-ischemia-reperfusion fibrosis.
Li Y et al.·Cell Signal
2025
Renal tubular VMP1 protects against acute kidney injury via modulating autophagy and autophagy-independent pathway.
Yang W et al.·Autophagy
2025Open Access
VMP1 attenuates ferroptosis and mitochondrial dysfunction in nucleus pulposus cells through the PINK1/Parkin-mediated mitophagy pathway.
Zhang Y et al.·J Orthop Surg Res
2025Open Access
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
VMP1: a multifaceted regulator of cellular homeostasis with implications in disease pathology
Tong J et al.·Front Cell Dev Biol
2024
Palmitoylation of vacuole membrane protein 1 promotes small extracellular vesicle secretion via interaction with ALIX and influences intercellular communication
Qu M et al.·Cell Commun Signal
2024
VMP1, a novel prognostic biomarker, contributes to glioma development by regulating autophagy
Lin W et al.·J Neuroinflammation
2021
Abnormal Vacuole Membrane Protein-1 Expression in Parkinson's Disease Patients
Al-Nusaif M et al.·Front Neurosci
2022Cohort
VMP1 inhibits the progression of breast cancer via regulating PI3K/AKT and MEK/ERK signaling pathway
Chen S et al.·Cancer Cell Int
2026
VMP1 Regulated by chi-miR-124a Effects Goat Myoblast Proliferation, Autophagy, and Apoptosis through the PI3K/ULK1/mTOR Signaling Pathway
Liu Y et al.·Cells
2022
Loss of hepatic VMP1 trapped VLDL in the bilayer of endoplasmic reticulum membrane .
Ni HM et al.·Liver Res
2023
TMEM41B and VMP1 are phospholipid scramblases.
Zhang T et al.·Autophagy
2021
Top 8 full-text resultsSearch PubTator3 ↗

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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients