VPS13C

protein-coding

vacuolar protein sorting 13 homolog C, the group of bridge-like lipid transfer protein family

Gene summary

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]

MANE transcript

NM_020821.3

Inheritance

ClinVar variants

P:94U:401B:290

Top phenotype

Parkinson disease 23, autosomal recessive, early onset

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr15:61,852,389-62,060,473

External References & Databases

Ensembl (ENSG00000129003)

Transcript & Mutation Effects

hg38 • Region Span ~208.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

schizophreniaNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0005090

Submitter: Labcorp Genetics (formerly Invitae)

young-onset Parkinson diseaseSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017279

Submitter: Orphanet

autosomal recessive early-onset Parkinson disease 23STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014796

Submitter: PanelApp Australia

autosomal recessive early-onset Parkinson disease 23MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014796

Submitter: Genomics England PanelApp

autosomal recessive early-onset Parkinson disease 23STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014796

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Parkinson disease 23, autosomal recessive, early onsetAR

Manifestation: Neurologic

Intervention: Neurologic

Rationale: Individuals have been described with levodopa response

Refs: 26942284

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VPS13C variants in ClinVar

10 Conditions Cataloged

not providedTotal: 898

VPS13C-related disorderTotal: 57

Autosomal recessive early-onset Parkinson disease 23Total: 51

Inborn genetic diseasesTotal: 37

not specifiedTotal: 32

Young-onset Parkinson diseaseTotal: 8

Parkinson diseaseTotal: 5

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020821.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			7 clinvar	206 clinvar	21 clinvar	234
missense	1 clinvar	1 clinvar	369 clinvar	46 clinvar	15 clinvar	432
nonsense	25 clinvar	18 clinvar	2 clinvar	1 clinvar		46
start loss						0
frameshift	22 clinvar	9 clinvar	2 clinvar			33
splice donor/acceptor (+/-2bp)	1 clinvar	17 clinvar	21 clinvar	1 clinvar		40
Total	49	45	401	254	36	785

Highest pathogenic variant AF is 0.00044137923

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020821.3	RefSeq	NP_065872.1	85	MANE Select
ENST00000644861.2	Ensembl	ENSP00000493560.2	85	MANE Select
NM_001018088.3	RefSeq	NP_001018098.1	82	Standard
NM_017684.5	RefSeq	NP_060154.3	83	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein targeting to vacuole
Golgi to endosome transport
mitochondrion organization
protein retention in Golgi apparatus
negative regulation of parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization

Cellular Component

cytoplasm
mitochondrial outer membrane
cytosol
extrinsic component of membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000261517
Coding exons: 85
Length: 208085
Individuals with no LoFs: 124995
Homozygous LoFs: 0
Heterozygous LoFs: 753
Defined: 125748
p: 0.00300

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.29	1994	1.84e+3	1.08	0.0000903	24642
Missense (PolyPhen)		575	583.44	0.98553		7973
Synonymous	-2.53	722	640	1.13	0.0000316	6963
Loss of Function	5.40	110	190	0.578	0.00000964	2546

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0020	0.0019	notable
Latino/Admixed American	0.0017	0.0016	notable
Ashkenazi Jewish	0.0011	0.0011	notable
East Asian	0.00074	0.00071	rare
Finnish	0.011	0.011	notable
European (Non-Finnish)	0.0032	0.0031	notable
South Asian	0.0017	0.0015	notable
Other	0.0027	0.0024	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Necessary for proper mitochondrial function and maintenance of mitochondrial transmembrane potential. Involved in the regulation of PINK1/PRKN-mediated mitophagy in response to mitochondrial depolarization. {ECO:0000269|PubMed:26942284}.;

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.971
RVIS EVS: -0.81
RVIS percentile EVS: 12.08

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.449

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	High	Medium	High