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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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VPS13C
vacuolar protein sorting 13 homolog C
Chromosome 15 Β· 15q22.2
NCBI Gene: 54832Ensembl: ENSG00000129003.19HGNC: HGNC:23594UniProt: Q709C8
89PubMed Papers
21Diseases
0Drugs
88Pathogenic Variants
FUNCTIONAL ROLE
Transporter
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
lipid dropletlysosomeendoplasmic reticulum membranelate endosomeYoung adult-onset ParkinsonismParkinson diseaseyoung-onset Parkinson diseaseneurodegenerative disease
✦AI Summary

VPS13C encodes a bridge-like lipid transfer protein that mediates lipid transport between the endoplasmic reticulum (ER) and other organelles, particularly late endosomes/lysosomes 1. The protein contains a tubular N-terminal domain with a hydrophobic cavity capable of solubilizing and transporting glycerolipids between membranes 1. VPS13C localizes to ER contact sites where it tethers ER membranes to late endosomes/lysosomes and lipid droplets 1. The protein functions as a sensor of lysosome stress, rapidly relocating from cytosol to damaged lysosome surfaces in a Rab7-dependent manner to facilitate ER-lysosome contacts and lipid delivery 2. In dopaminergic neurons, VPS13C regulates lysosomal morphology, dynamics, motility, and hydrolytic activity through interactions with phospho-Rab10 3. Loss-of-function mutations in VPS13C cause autosomal recessive early-onset Parkinson's disease (PARK23) and dementia with Lewy bodies 45. VPS13C depletion leads to lysosomal dysfunction with altered lipid profiles, accumulation of mitochondrial DNA in the cytosol, and inappropriate activation of the cGAS-STING innate immune pathway 6. These findings implicate defects in ER-lysosome lipid homeostasis as a key mechanism in VPS13C-related neurodegeneration.

Sources cited
1
VPS13C is a lipid transfer protein with tubular N-terminal domain that localizes to ER contact sites
PMID: 30093493
2
VPS13C functions as a sensor of lysosome damage and facilitates ER-lysosome contacts in a Rab7-dependent manner
PMID: 40211074
3
VPS13C regulates lysosomal function in dopaminergic neurons through phospho-Rab10 interactions
PMID: 38358348
4
VPS13C mutations cause autosomal recessive early-onset Parkinson's disease
PMID: 35328025
5
VPS13C mutations are associated with early-onset Parkinson's disease and dementia with Lewy bodies
PMID: 34875562
6
VPS13C depletion causes lysosomal dysfunction and inappropriate cGAS-STING pathway activation
PMID: 35657605
Disease Associationsβ“˜21
Young adult-onset ParkinsonismOpen Targets
0.72Strong
Parkinson diseaseOpen Targets
0.54Moderate
young-onset Parkinson diseaseOpen Targets
0.50Moderate
neurodegenerative diseaseOpen Targets
0.45Moderate
type 2 diabetes mellitusOpen Targets
0.45Moderate
diabetes mellitusOpen Targets
0.41Moderate
Abnormality of the skeletal systemOpen Targets
0.39Weak
systemic lupus erythematosusOpen Targets
0.31Weak
preeclampsiaOpen Targets
0.30Weak
complicationOpen Targets
0.29Weak
metabolic syndromeOpen Targets
0.29Weak
diabetic eye diseaseOpen Targets
0.28Weak
hemorrhageOpen Targets
0.27Weak
genetic disorderOpen Targets
0.19Weak
response to radiationOpen Targets
0.17Weak
open-angle glaucomaOpen Targets
0.16Weak
diabetic neuropathyOpen Targets
0.15Weak
diabetic retinopathyOpen Targets
0.15Weak
glaucomaOpen Targets
0.15Weak
type 2 diabetes nephropathyOpen Targets
0.13Weak
Parkinson disease 23, autosomal recessive, early onsetUniProt
Pathogenic Variants88
NM_020821.3(VPS13C):c.10060G>T (p.Glu3354Ter)Pathogenic
Autosomal recessive early-onset Parkinson disease 23|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 3354
NM_020821.3(VPS13C):c.1111C>T (p.Arg371Ter)Pathogenic
Autosomal recessive early-onset Parkinson disease 23|Young-onset Parkinson disease|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 371
NM_020821.3(VPS13C):c.8806C>T (p.Arg2936Ter)Pathogenic
Autosomal recessive early-onset Parkinson disease 23|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 2936
NM_020821.3(VPS13C):c.1193_1194del (p.Ile398fs)Pathogenic
Autosomal recessive early-onset Parkinson disease 23
β˜…β˜…β˜†β˜†2025β†’ Residue 398
NM_020821.3(VPS13C):c.4429dup (p.Ile1477fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 1477
NM_020821.3(VPS13C):c.10954C>T (p.Arg3652Ter)Pathogenic
not provided|Autosomal recessive early-onset Parkinson disease 23
β˜…β˜…β˜†β˜†2025β†’ Residue 3652
NM_020821.3(VPS13C):c.4165G>C (p.Gly1389Arg)Pathogenic
Autosomal recessive early-onset Parkinson disease 23|Parkinson disease|Young-onset Parkinson disease|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 1389
NM_020821.3(VPS13C):c.5868+1G>ALikely pathogenic
not provided|Autosomal recessive early-onset Parkinson disease 23
β˜…β˜…β˜†β˜†2024
NM_020821.3(VPS13C):c.7382dup (p.Asn2461fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 2461
NM_020821.3(VPS13C):c.5245C>T (p.Gln1749Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1749
NM_020821.3(VPS13C):c.6609+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_020821.3(VPS13C):c.7009dup (p.Glu2337fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 2337
NM_020821.3(VPS13C):c.9152G>A (p.Trp3051Ter)Pathogenic
Autosomal recessive early-onset Parkinson disease 23
β˜…β˜†β˜†β˜†2025β†’ Residue 3051
NM_020821.3(VPS13C):c.3169del (p.Gln1057fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1057
NM_020821.3(VPS13C):c.1398del (p.Gly467fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 467
NM_020821.3(VPS13C):c.192del (p.Lys64fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 64
NM_020821.3(VPS13C):c.8074G>T (p.Glu2692Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 2692
NM_020821.3(VPS13C):c.5462dup (p.Leu1821fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1821
NM_020821.3(VPS13C):c.8972_8975del (p.Lys2991fs)Pathogenic
Autosomal recessive early-onset Parkinson disease 23
β˜…β˜†β˜†β˜†2025β†’ Residue 2991
NM_020821.3(VPS13C):c.4836_4839del (p.Cys1613fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1613
View on ClinVar β†—
Related Genes
VPS35Protein interaction94%PLA2G6Protein interaction77%DNAJC13Protein interaction72%ATP13A2Protein interaction72%VPS13DShared pathway67%VPS13AShared pathway63%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
82%
Lung
62%
Heart
55%
Brain
54%
Liver
28%
Gene Interaction Network
Click a node to explore
VPS13CVPS35PLA2G6DNAJC13ATP13A2VPS13DVPS13A
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q709C8
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.86LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.77 [0.70–0.86]
RankingsWhere VPS13C stands among ~20K protein-coding genes
  • #5,392of 20,598
    Most Researched89
  • #859of 5,498
    Most Pathogenic Variants88 Β· top quartile
  • #7,482of 17,882
    Most Constrained (LOEUF)0.86
Genes detectedVPS13C
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Monogenic Parkinson's Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing.
PMID: 35328025
Genes (Basel) Β· 2022
1.00
2
VPS13A and VPS13C are lipid transport proteins differentially localized at ER contact sites.
PMID: 30093493
J Cell Biol Β· 2018
0.90
3
ER-lysosome lipid transfer protein VPS13C/PARK23 prevents aberrant mtDNA-dependent STING signaling.
PMID: 35657605
J Cell Biol Β· 2022
0.80
4
The bridge-like lipid transport protein VPS13C/PARK23 mediates ER-lysosome contacts following lysosome damage.
PMID: 40211074
Nat Cell Biol Β· 2025
0.70
5
Two novel variants of VPS13C gene related Parkinsonism: A case report and literature review.
PMID: 41517720
Medicine (Baltimore) Β· 2026
0.60