VPS13C

Chr 15AR

vacuolar protein sorting 13 homolog C

Also known as: BLTP5C, PARK23

NCBI Gene: 54832 ENSG00000129003 UniProt: Q709C8 OMIM: 608879

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).

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Involved in mitochondrion organization and negative regulation of type 2 mitophagy. Located in several cellular components, including late endosome; lipid droplet; and mitochondrial outer membrane. Implicated in Parkinson's disease 23. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Parkinson disease 23, early onsetMIM #616840

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Parkinson disease 23, early onset; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.68

LOEUF

Mechanism· predicted

📖

GeneReview available — VPS13C

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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 OE?0.58 (0.49–0.68)

0≤0.351.4

Missense OE?1.08 (1.04–1.13)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 110 / 190.3Missense obs/exp: 1994 / 1838.8Syn Z: -2.53

Background carrier burden — how many people carry a rare variant somewhere in VPS13C?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 14

5,165 rare PASS variants

Rare truncating (LoF)

1 in 210

711 rare PASS variants

Rare synonymous (reference)

1 in 28

1,685 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for VPS13C. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

Exome coverage (gnomAD): 58 of 85 coding exons well covered in gnomAD exomes; exons 1, 2, 4, 5, 6 and 22 more marginal. Genomes: 84 of 85 (exon 12 below).? see exons ↓