VPS13C

Chr 15AR

vacuolar protein sorting 13 homolog C

Also known as: BLTP5C, PARK23

NCBI Gene: 54832ENSG00000129003UniProt: Q709C8

The VPS13C protein mediates lipid transfer between membranes at organelle contact sites and is necessary for proper mitochondrial function and maintenance of mitochondrial transmembrane potential. Biallelic mutations cause autosomal recessive early-onset Parkinson disease (Parkinson disease 23). The gene shows moderate constraint against loss-of-function variants (LOEUF 0.677).

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Parkinson disease 23, autosomal recessive, early onsetMIM #616840
AR
0
Active trials
21
Pubs (1 yr)
52
P/LP submissions
0%
P/LP missense
0.68
LOEUF
DN
Mechanism· predicted
Clinical Summary— VPS13C
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
47 unique Pathogenic / Likely Pathogenic· 177 VUS of 500 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — VPS13C
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.68LOEUF
pLI 0.000
Z-score 5.40
OE 0.58 (0.49–0.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-1.29Z-score
OE missense 1.08 (1.04–1.13)
1994 obs / 1838.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.58 (0.49–0.68)
0≤0.351.4
Missense OE1.08 (1.04–1.13)
0≤0.61.4
Synonymous OE1.13
0≤1.21.6
LoF obs/exp: 110 / 190.3Missense obs/exp: 1994 / 1838.8Syn Z: -2.53
DN
0.6551th %ile
GOF
0.5954th %ile
LOF
0.2678th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic20
VUS177
Likely Benign133
Benign70
Conflicting4
27
Pathogenic
20
Likely Pathogenic
177
VUS
133
Likely Benign
70
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
0
16
0
27
Likely Pathogenic
13
0
7
0
20
VUS
2
158
14
3
177
Likely Benign
0
4
56
73
133
Benign
0
3
59
8
70
Conflicting
—4
Total2616515284431

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

View in ClinVar →

Protein Context — Lollipop Plot

VPS13C · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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