VPS13C

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

Basic information

Region (hg38): 15:61852389-62060473

Links

ENSG00000129003 ∙ NCBI:54832 ∙ OMIM:608879 ∙ HGNC:23594 ∙ Uniprot:Q709C8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive early-onset Parkinson disease 23 (Moderate), mode of inheritance: AR
• schizophrenia (No Known Disease Relationship), mode of inheritance: Unknown
• autosomal recessive early-onset Parkinson disease 23 (Strong), mode of inheritance: AR
• young-onset Parkinson disease (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Parkinson disease 23, autosomal recessive, early onset	AR	Neurologic	Individuals have been described with levodopa response	Neurologic	26942284

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS13C gene.

• not_provided (879 variants)
• VPS13C-related_disorder (57 variants)
• Autosomal_recessive_early-onset_Parkinson_disease_23 (47 variants)
• Inborn_genetic_diseases (37 variants)
• not_specified (32 variants)
• Young-onset_Parkinson_disease (8 variants)
• Parkinson_disease (5 variants)
• EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
• Primary_degenerative_dementia_of_the_Alzheimer_type,_presenile_onset (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS13C gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020821.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	196	22	225
missense	1	1	363	46	15	426
nonsense	24	16	2	1		43
start loss						0
frameshift	22	9	2			33
splice donor/acceptor (+/-2bp)	1	16	21	1		39
Total	48	42	395	244	37

Highest pathogenic variant AF is 0.00044137923

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS13C	protein_coding	protein_coding	ENST00000261517	85	208085

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		124995	0	753	125748	0.00300

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.29	1994	1.84e+3	1.08	0.0000903	24642
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00369	0.00362
Ashkenazi Jewish	0.00110	0.00109
East Asian	0.000744	0.000707
Finnish	0.0110	0.0108
European (Non-Finnish)	0.00319	0.00307
Middle Eastern	0.000744	0.000707
South Asian	0.00167	0.00154
Other	0.00268	0.00245

dbNSFP

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_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.449

Gene Damage Prediction

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

Gene ontology

• 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