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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
VPS4A
vacuolar protein sorting 4 homolog A
Chromosome 16 Β· 16q22.1
NCBI Gene: 27183Ensembl: ENSG00000132612.18HGNC: HGNC:13488UniProt: Q9UN37
174PubMed Papers
21Diseases
0Drugs
6Pathogenic Variants
FUNCTIONAL ROLE
Transporter
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
midbodyprotein bindingATP bindingATP hydrolysis activitycerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndromeviral diseaseHIV infectiongenetic disorder
✦AI Summary

VPS4A (vacuolar protein sorting 4 homolog A) is an AAA+ ATPase that serves multiple critical cellular functions through its role in membrane fission processes. The protein functions as a selective receptor for lipophagy, where phosphorylation at Ser95,97 drives its localization to lipid droplets during fasting, mediating their degradation in lysosomes in an autophagy-dependent manner 1. VPS4A also plays a unique regulatory role in cytokinetic abscission, distinct from its paralog VPS4B, by binding abscission checkpoint proteins CHMP4C and ANCHR and functioning in earlier stages of cell division 2. As part of the ESCRT machinery, VPS4A mediates phagophore closure during autophagy processes, including virus-induced mitophagy where it is recruited by viral proteins to facilitate mitochondrial clearance 3. The protein has been identified as a therapeutic target, as compounds like aloperine can bind VPS4A (at residues F153 and D263) to inhibit autophagosome-lysosome fusion, leading to cancer cell apoptosis 4. Clinically, de novo mutations in VPS4A have been associated with intellectual disability, highlighting its importance in neurodevelopment 5. VPS4A levels are reduced in human steatotic livers, indicating its significance in metabolic liver diseases 1.

Sources cited
1
VPS4A functions as selective receptor for lipophagy through Ser95,97 phosphorylation and is reduced in steatotic livers
PMID: 39520981
2
VPS4A has unique regulatory role in cytokinetic abscission, binding checkpoint proteins CHMP4C and ANCHR
PMID: 38687820
3
VPS4A mediates phagophore closure during virus-induced mitophagy
PMID: 40574328
4
VPS4A can be therapeutically targeted by aloperine at residues F153 and D263 to inhibit autophagy
PMID: 39166458
5
De novo mutations in VPS4A are associated with intellectual disability
PMID: 25356899
Disease Associationsβ“˜21
cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndromeOpen Targets
0.75Strong
viral diseaseOpen Targets
0.47Moderate
HIV infectionOpen Targets
0.46Moderate
genetic disorderOpen Targets
0.19Weak
breast carcinomaOpen Targets
0.15Weak
cancerOpen Targets
0.09Suggestive
infectionOpen Targets
0.06Suggestive
colorectal carcinomaOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.06Suggestive
lower respiratory tract diseaseOpen Targets
0.06Suggestive
early-onset non-syndromic cataractOpen Targets
0.05Suggestive
oral squamous cell carcinomaOpen Targets
0.05Suggestive
Cataract-microcornea syndromeOpen Targets
0.05Suggestive
neutropenia, severe congenital, 9, autosomal dominantOpen Targets
0.05Suggestive
Familial ocular anterior segment mesenchymal dysgenesisOpen Targets
0.05Suggestive
Partial congenital cataractOpen Targets
0.04Suggestive
Cataract with Y-shaped suture opacitiesOpen Targets
0.04Suggestive
Total congenital cataractOpen Targets
0.04Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.04Suggestive
galactosemia 4Open Targets
0.04Suggestive
CIMDAG syndromeUniProt
Pathogenic Variants6
NM_013245.3(VPS4A):c.83C>T (p.Ala28Val)Likely pathogenic
Syndromic congenital hemolytic and dyserythropoietic anemia|Cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome
β˜…β˜…β˜†β˜†2023β†’ Residue 28
NM_013245.3(VPS4A):c.850A>T (p.Arg284Trp)Pathogenic
not provided|Syndromic congenital hemolytic and dyserythropoietic anemia|Cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome
β˜…β˜…β˜†β˜†2020β†’ Residue 284
NM_013245.3(VPS4A):c.346G>A (p.Ala116Thr)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 116
NM_013245.3(VPS4A):c.616G>A (p.Glu206Lys)Pathogenic
not provided|Cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome
β˜…β˜†β˜†β˜†2020β†’ Residue 206
NM_013245.3(VPS4A):c.850A>G (p.Arg284Gly)Pathogenic
not provided|Cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome
β˜…β˜†β˜†β˜†2020β†’ Residue 284
NM_013245.3(VPS4A):c.608G>A (p.Gly203Glu)Pathogenic
Syndromic congenital hemolytic and dyserythropoietic anemia|Cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome
β˜…β˜†β˜†β˜†2020β†’ Residue 203
View on ClinVar β†—
Related Genes
CHMP3Protein interaction100%VPS25Protein interaction97%RNF103-CHMP3Protein interaction97%VPS36Protein interaction96%TSG101Protein interaction95%HGSProtein interaction95%
Tissue Expression6 tissues
Brain
100%
Lung
73%
Heart
70%
Ovary
68%
Liver
66%
Bone Marrow
49%
Gene Interaction Network
Click a node to explore
VPS4ACHMP3VPS25RNF103-CHMP3VPS36TSG101HGS
PROTEIN STRUCTURE
Preparing viewer…
PDB1YXR Β· NMR
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.58Moderately Constrained
pLIβ“˜
0.40Tolerant
Observed/Expected LoF0.40 [0.28–0.58]
RankingsWhere VPS4A stands among ~20K protein-coding genes
  • #2,536of 20,598
    Most Researched174 Β· top quartile
  • #3,320of 5,498
    Most Pathogenic Variants6
  • #3,931of 17,882
    Most Constrained (LOEUF)0.58 Β· top quartile
Genes detectedVPS4A
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Aloperine Suppresses Cancer Progression by Interacting with VPS4A to Inhibit Autophagosome-lysosome Fusion in NSCLC.
PMID: 39166458
Adv Sci (Weinh) Β· 2024
1.00
2
VPS4A is the selective receptor for lipophagy in mice and humans.
PMID: 39520981
Mol Cell Β· 2024
0.90
3
The human AAA-ATPase VPS4A isoform and its co-factor VTA1 have a unique function in regulating mammalian cytokinesis abscission.
PMID: 38687820
PLoS Biol Β· 2024
0.80
4
De novo mutations in moderate or severe intellectual disability.
PMID: 25356899
PLoS Genet Β· 2014
0.70
5
Mitochondrial phosphatase PPTC7 promotes EGFR recycling by facilitating VPS4A endosomal localization.
PMID: 39776116
J Cell Sci Β· 2025
0.60