VPS13C

Summary

VPS13C (vacuolar protein sorting 13 homolog C, HGNC:23594) is a protein-coding gene on chromosome 15q22.2, encoding Intermembrane lipid transfer protein VPS13C (Q709C8). Mediates the transfer of lipids between membranes at organelle contact sites.

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.

Source: NCBI Gene 54832 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive early-onset Parkinson disease 23 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 27
• Clinical variants (ClinVar): 1,183 total — 49 pathogenic, 38 likely-pathogenic
• Phenotypes (HPO): 56
• MANE Select transcript: NM_020821

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23594
Approved symbol	VPS13C
Name	vacuolar protein sorting 13 homolog C
Location	15q22.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20136, FLJ10381, KIAA1421, BLTP5C, PARK23
Ensembl gene	ENSG00000129003
Ensembl biotype	protein_coding
OMIM	608879
Entrez	54832

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 5 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000249837, ENST00000395898, ENST00000558088, ENST00000558338, ENST00000558919, ENST00000559119, ENST00000560637, ENST00000561258, ENST00000644861, ENST00000645819, ENST00000649766, ENST00000650094

RefSeq mRNA: 4 — MANE Select: NM_020821 NM_001018088, NM_017684, NM_018080, NM_020821

CCDS: CCDS10180, CCDS32257, CCDS45272, CCDS58367

Canonical transcript exons

ENST00000644861 — 85 exons

Exon	Start	End
ENSE00000449794	62033441	62033542
ENSE00000449795	62023411	62023520
ENSE00000691901	61869500	61869623
ENSE00000691904	61871989	61872034
ENSE00000691906	61873246	61873409
ENSE00000691909	61874876	61874951
ENSE00000691912	61875732	61875845
ENSE00000691913	61876973	61877054
ENSE00000691916	62020479	62020538
ENSE00000691940	62034957	62035052
ENSE00000885035	61863440	61863528
ENSE00000885036	61868659	61868773
ENSE00000885039	61907264	61907390
ENSE00000885046	61961589	61961893
ENSE00000885047	61962371	61962538
ENSE00000885048	61962749	61962852
ENSE00000885049	61963835	61963951
ENSE00000885050	61964699	61964861
ENSE00000885051	61966083	61966142
ENSE00000885052	61967368	61967447
ENSE00000885053	61969299	61969452
ENSE00000885054	61972625	61972764
ENSE00000885055	61973454	61973532
ENSE00000885056	61974288	61974417
ENSE00000885057	61977082	61977199
ENSE00000885058	61978626	61978749
ENSE00000885059	61981342	61981478
ENSE00000885060	61982459	61982573
ENSE00000885061	61983820	61984012
ENSE00001124906	61991673	61991802
ENSE00001124912	62000564	62000626
ENSE00001124918	62007308	62007479
ENSE00001124921	62008655	62008761
ENSE00001124928	62010472	62010599
ENSE00001124934	62012107	62012164
ENSE00001124940	62013039	62013119
ENSE00001124945	62013933	62013992
ENSE00001124969	62023780	62023845
ENSE00001124977	62028358	62028420
ENSE00001124997	62041324	62041366
ENSE00001125004	62044212	62044255
ENSE00001141332	61917341	61917635
ENSE00001364505	61929501	61929748
ENSE00001364815	61882596	61882736
ENSE00001365089	61884128	61884269
ENSE00001366228	61890165	61890400
ENSE00001367186	61946307	61946410
ENSE00001368434	61936597	61936750
ENSE00001368668	61950945	61951024
ENSE00001368990	61920067	61920331
ENSE00001369254	61920498	61920647
ENSE00001369856	61919289	61919449
ENSE00001376939	61927091	61927320
ENSE00001377148	61881747	61881828
ENSE00001377714	61931090	61931259
ENSE00001377851	61947193	61947309
ENSE00001380396	61925456	61925548
ENSE00001380447	61922397	61922762
ENSE00001381916	61941763	61942067
ENSE00001382850	61921947	61922033
ENSE00001383901	61940647	61940794
ENSE00001386895	61945715	61945882
ENSE00001387621	61949443	61949605
ENSE00001387780	61950358	61950417
ENSE00001388814	61881563	61881632
ENSE00001390310	61954421	61954554
ENSE00001390418	61918136	61918257
ENSE00001391492	61934219	61934331
ENSE00001484949	61951824	61951980
ENSE00003458524	61880609	61880722
ENSE00003468194	61959448	61959595
ENSE00003468572	61984857	61984999
ENSE00003473429	61908992	61909125
ENSE00003476870	61958608	61958716
ENSE00003497191	61878607	61878746
ENSE00003529938	61913311	61913415
ENSE00003568464	61910177	61910305
ENSE00003584041	61915633	61916022
ENSE00003607544	61911840	61912004
ENSE00003610533	61856286	61856409
ENSE00003627789	61854871	61854954
ENSE00003629706	61991000	61991094
ENSE00003689655	61880843	61880954
ENSE00003900585	62060275	62060447
ENSE00003902673	61852389	61854558

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 97.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.0321 / max 1031.2089, expressed in 1816 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150363	53.8470	1814
150364	2.9947	1237
150366	0.1424	34
150365	0.0481	12

Top tissues by expression

292 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.61	gold quality
upper leg skin	UBERON:0004262	96.96	gold quality
epithelium of nasopharynx	UBERON:0001951	96.88	gold quality
nasopharynx	UBERON:0001728	96.86	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.86	gold quality
colonic epithelium	UBERON:0000397	96.72	gold quality
visceral pleura	UBERON:0002401	96.60	gold quality
corpus callosum	UBERON:0002336	96.48	gold quality
palpebral conjunctiva	UBERON:0001812	96.43	gold quality
pylorus	UBERON:0001166	95.96	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.90	gold quality
superficial temporal artery	UBERON:0001614	95.83	gold quality
skin of hip	UBERON:0001554	95.77	gold quality
bronchial epithelial cell	CL:0002328	95.74	gold quality
pleura	UBERON:0000977	95.74	gold quality
tendon	UBERON:0000043	95.50	gold quality
germinal epithelium of ovary	UBERON:0001304	95.48	gold quality
epithelium of bronchus	UBERON:0002031	95.47	gold quality
bronchus	UBERON:0002185	95.46	gold quality
urethra	UBERON:0000057	95.43	gold quality
parietal pleura	UBERON:0002400	95.36	gold quality
pituitary gland	UBERON:0000007	95.28	gold quality
endometrium	UBERON:0001295	95.09	gold quality
choroid plexus epithelium	UBERON:0003911	95.02	gold quality
blood vessel layer	UBERON:0004797	94.97	gold quality
monocyte	CL:0000576	94.91	gold quality
mononuclear cell	CL:0000842	94.91	gold quality
mammary duct	UBERON:0001765	94.91	gold quality
peripheral nervous system	UBERON:0000010	94.83	gold quality
tibial nerve	UBERON:0001323	94.83	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.19
E-HCAD-29	no	211.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

113 targeting VPS13C, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867

Literature-anchored findings (GeneRIF, showing 21)

• The diabetogenic VPS13C/C2CD4A/C2CD4B rs7172432 A allele associates with glucose-stimulated insulin response in non-diabetic individuals from the general population, suggesting an impaired beta cell function as an intermediary diabetes-related trait. (PMID:21249489)
• The role of four loci (ADCY5, GIPR, GCKR and VPS13C) in early impairment of glucose and insulin metabolism in children, was investigated. (PMID:21789219)
• no detectable effect (with an OR >2.1) of the variants in GCKR, GIPR, ADCY5 and VPS13C on the response to sulfonylurea treatment, indicating that these variants are not significantly contributing to the risk of SH in patients with T2D (PMID:22956255)
• We describe truncating mutations in VPS13C associated with early-onset parkinsonism with rapid progression and widely distributed Lewy bodies. (PMID:26942284)
• The present data thus provide evidence for a limited role for changes in VPS13C expression in conferring altered type 2 diabetes risk at this locus, particularly in females, and suggest that C2CD4A, but not C2CD4B, may also be involved. (PMID:27329800)
• This study found that rs2414739 (VPS13C) is associated with Parkinson disease in IRAN population. (PMID:27653855)
• Our results suggest that rs329648 is associated with risk of developing PD in the Han Chinese population. Our findings should be verified in further studies, and they highlight the need for functional studies of MIR4697. (PMID:28380328)
• Despite the low diagnostic yield of exome sequencing in sporadic early-onset PD, the confirmation of the recently discovered VPS13C gene highlights its advantage over using predefined gene panels. (PMID:28862745)
• human VPS13A and VPS13C bind to the ER, tethering it to mitochondria (VPS13A), to late endosome/lysosomes (VPS13C), and to lipid droplets (both VPS13A and VPS13C). (PMID:30093493)
• Knockdown of VPS13C-has-circ-001567 significantly promoted apoptosis and inhibited the proliferation of SKOV3 and OV-1063 cells in vitro. Knockdown of VPS13C-has-circ-001567 led to cell cycle arrest at G1 phase and decreased the percentage of S1 phase cells. Knockdown of VPS13C-has-circ-001567 decreased the invasion ability of SKOV3 and OV-1063 cells. (PMID:30376358)
• the identification and characterization of a large L1 retrotransposition-mediated VPS13C deletion in a patient with parkinsonism (PMID:30452786)
• Mutation screening and burden analysis of VPS13C in Chinese patients with early-onset Parkinson’s disease. (PMID:32507414)
• Familial dementia with Lewy bodies with VPS13C mutations. (PMID:33039764)
• TBC1D1 interacting proteins, VPS13A and VPS13C, regulate GLUT4 homeostasis in C2C12 myotubes. (PMID:33087848)
• Contribution of rare homozygous and compound heterozygous VPS13C missense mutations to dementia with Lewy bodies and Parkinson’s disease. (PMID:33579389)
• Association between VPS13C rs2414739 polymorphism and Parkinson’s disease risk: A meta-analysis. (PMID:33838259)
• VPS13C-associated Parkinson’s disease: Two novel cases and review of the literature. (PMID:34875562)
• ER-lysosome lipid transfer protein VPS13C/PARK23 prevents aberrant mtDNA-dependent STING signaling. (PMID:35657605)
• In situ architecture of the lipid transport protein VPS13C at ER-lysosome membrane contacts. (PMID:35858323)
• VPS13C regulates phospho-Rab10-mediated lysosomal function in human dopaminergic neurons. (PMID:38358348)
• VPS13C and STING expression in neuropsychiatric systemic lupus erythematosus: unveiling an unbreached territory. (PMID:39306342)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	vps13c	ENSDARG00000074465
mus_musculus	Vps13c	ENSMUSG00000035284
rattus_norvegicus	Vps13c	ENSRNOG00000030213
drosophila_melanogaster	Vps13	FBGN0033194
caenorhabditis_elegans	vps-13	WBGENE00011629

Paralogs (2): VPS13D (ENSG00000048707), VPS13A (ENSG00000197969)

Protein

Protein identifiers

Intermembrane lipid transfer protein VPS13C — Q709C8 (reviewed: Q709C8)

Alternative names: Vacuolar protein sorting-associated protein 13C

All UniProt accessions (3): Q709C8, A0A3B3IT88, A0A3B3IU50

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the transfer of lipids between membranes at organelle contact sites. 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.

Subcellular location. Mitochondrion outer membrane. Lipid droplet. Endoplasmic reticulum membrane. Lysosome membrane. Late endosome membrane.

Tissue specificity. Widely expressed.

Disease relevance. Parkinson disease 23, autosomal recessive, early onset (PARK23) [MIM:616840] An autosomal recessive, early-onset form of Parkinson disease, a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The FFAT motif is required for localization to the endoplasmic reticulum.

Similarity. Belongs to the VPS13 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q709C8-1	1, 2A	yes
Q709C8-2	2, 2B
Q709C8-3	3, 1A
Q709C8-4	4, 1B

RefSeq proteins (4): NP_001018098, NP_060154, NP_060550, NP_065872* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009543	VPS13_VAB	Domain
IPR026847	VPS13	Family
IPR026854	VPS13_N	Domain
IPR056747	VPS13-like_M	Domain
IPR056748	VPS13-like_C	Domain

Pfam: PF12624, PF25033, PF25036, PF25037

UniProt features (39 total): modified residue 14, sequence variant 12, splice variant 3, region of interest 3, domain 2, compositionally biased region 2, chain 1, mutagenesis site 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q709C8 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (14): 614, 619, 624, 737, 842, 872, 874, 1979, 2473, 3519, 3526, 3538, 3641, 132

Mutagenesis-validated functional residues (1):

Position	Phenotype
878–879	abnormal localization to the cytosol.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 334 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_AUTOPHAGY, KOBAYASHI_EGFR_SIGNALING_24HR_UP, TGCGCANK_UNKNOWN, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_PROTEIN_TARGETING, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, CEBPB_01, GOBP_MACROAUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_AUTOPHAGY, GOBP_RESPONSE_TO_INSULIN

GO Biological Process (7): protein targeting to vacuole (GO:0006623), lipid transport (GO:0006869), Golgi to endosome transport (GO:0006895), mitochondrion organization (GO:0007005), response to insulin (GO:0032868), protein retention in Golgi apparatus (GO:0045053), negative regulation of type 2 mitophagy (GO:1905090)

GO Molecular Function (0):

GO Cellular Component (15): cytoplasm (GO:0005737), mitochondrial outer membrane (GO:0005741), lysosome (GO:0005764), lysosomal membrane (GO:0005765), late endosome (GO:0005770), endoplasmic reticulum membrane (GO:0005789), lipid droplet (GO:0005811), cytosol (GO:0005829), late endosome membrane (GO:0031902), dense core granule membrane (GO:0032127), extracellular exosome (GO:0070062), mitochondrion (GO:0005739), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	3
intracellular membrane-bounded organelle	2
endomembrane system	2
protein targeting	1
intracellular protein transport	1
vacuolar transport	1
protein localization to vacuole	1
establishment of protein localization to vacuole	1
transport	1
lipid localization	1
post-Golgi vesicle-mediated transport	1
intercellular transport	1
cytosolic transport	1
organelle organization	1
response to peptide hormone	1
maintenance of protein location in cell	1
protein localization to Golgi apparatus	1
type 2 mitophagy	1
negative regulation of mitophagy	1
regulation of type 2 mitophagy	1
intracellular anatomical structure	1
mitochondrial membrane	1
organelle outer membrane	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
endosome	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular membraneless organelle	1
late endosome	1
endosome membrane	1
secretory granule membrane	1
dense core granule	1
extracellular vesicle	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1794 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VPS13C	ATP13A2	Q9NQ11	759
VPS13C	VPS35	Q96QK1	751
VPS13C	DNAJC6	O75061	748
VPS13C	PLA2G6	O60733	700
VPS13C	TMEM230	Q96A57	693
VPS13C	DNAJC13	O75165	691
VPS13C	FBXO7	Q9Y3I1	682
VPS13C	CHCHD2	Q9Y6H1	671
VPS13C	SYNJ1	O43426	671
VPS13C	PINK1	Q9BXM7	654
VPS13C	GBA1	P04062	652
VPS13C	PRKN	O60260	648
VPS13C	PDZD8	Q8NEN9	622
VPS13C	LRRK2	Q5S007	605
VPS13C	RAB39B	Q96DA2	605

IntAct

88 interactions, top by confidence:

A	B	Type	Score
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
ARPC5	ARPC3	psi-mi:“MI:0914”(association)	0.730
GBA2	ILVBL	psi-mi:“MI:0914”(association)	0.640
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.640
DNAJC7	PLD2	psi-mi:“MI:0914”(association)	0.640
FAF2	UBB	psi-mi:“MI:0914”(association)	0.640
VAPA	PITPNM1	psi-mi:“MI:0914”(association)	0.640
UBXN4	UBE4A	psi-mi:“MI:0914”(association)	0.620
RAB9A	CHM	psi-mi:“MI:0914”(association)	0.610
TMEM31	PSMD11	psi-mi:“MI:0914”(association)	0.530
RNF19B	PIK3R2	psi-mi:“MI:0914”(association)	0.530
RAB30	UBB	psi-mi:“MI:0914”(association)	0.530
RAB1A	CHM	psi-mi:“MI:0914”(association)	0.530
FAM78B	RPS27A	psi-mi:“MI:0914”(association)	0.530
LGALS12	EMB	psi-mi:“MI:0914”(association)	0.530
RAB1B	CHM	psi-mi:“MI:0914”(association)	0.530
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
VPS13C	HNRNPK	psi-mi:“MI:0915”(physical association)	0.400
VPS13C	HSP90B1	psi-mi:“MI:0915”(physical association)	0.400
VPS13C	HNRNPA2B1	psi-mi:“MI:0915”(physical association)	0.400
IER3IP1	VPS13C	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
P		psi-mi:“MI:0914”(association)	0.350

BioGRID (174): VPS13C (Affinity Capture-MS), VPS13C (Affinity Capture-MS), VPS13C (Affinity Capture-MS), VPS13C (Affinity Capture-MS), VPS13C (Affinity Capture-MS), VPS13C (Affinity Capture-MS), VPS13C (Affinity Capture-MS), VPS13C (Affinity Capture-MS), VPS13C (Affinity Capture-MS), VPS13C (Affinity Capture-MS), VPS13C (Affinity Capture-MS), VPS13C (Affinity Capture-MS), VPS13C (Affinity Capture-MS), VPS13C (Affinity Capture-MS), VPS13C (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IXF6, A0JMR6, A0JNW5, A2RSJ4, F4HRV8, O17482, O95876, P49021, P79457, Q08D51, Q28C33, Q3B7T1, Q3UD82, Q498F0, Q5H8C4, Q5JSH3, Q5JTW2, Q5QNQ6, Q5R9R1, Q5THJ4, Q5ZLG9, Q6BDS2, Q6GLR7, Q6GQV7, Q6INA9, Q6NRZ1, Q6NVE8, Q6ZMT4, Q6ZWJ1, Q709C8, Q80T23, Q80XK6, Q812E4, Q8BX70, Q8BXR9, Q8C5W4, Q8IWB9, Q8N3A8, Q8N7X0, Q8TDW5

Diamond homologs: Q21480, Q5H8C4, Q709C8, Q8BX70, Q96RL7, Q9BGZ0, Q7Z7G8, Q80TY5, Q54KX3, Q5THJ4, Q86K84, A2RSJ4, G0S3B8, Q54PG5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 118 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RAB geranylgeranylation	10	20.6×	3e-08
Dengue Virus Genome Translation and Replication	5	18.9×	8e-04
RHOF GTPase cycle	5	15.4×	1e-03
AUF1 (hnRNP D0) binds and destabilizes mRNA	5	14.8×	1e-03
RHOD GTPase cycle	6	14.6×	8e-04
Hh mutants are degraded by ERAD	5	14.5×	1e-03
SPOP-mediated proteasomal degradation of PD-L1(CD274)	5	13.6×	2e-03
Defective CFTR causes cystic fibrosis	5	13.1×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
endoplasmic reticulum to Golgi vesicle-mediated transport	7	9.1×	2e-03
Golgi organization	7	8.9×	2e-03
ERAD pathway	5	8.6×	9e-03
vesicle-mediated transport	9	8.2×	4e-04
endocytosis	7	6.3×	5e-03
protein transport	13	5.4×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1183 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	49
Likely pathogenic	38
Uncertain significance	384
Likely benign	382
Benign	216

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1323752	NM_020821.3(VPS13C):c.9541C>T (p.Arg3181Ter)	Pathogenic
1323753	NM_020821.3(VPS13C):c.10060G>T (p.Glu3354Ter)	Pathogenic
1323755	NM_020821.3(VPS13C):c.5842_5843insATGA (p.Ile1948fs)	Pathogenic
1354775	NM_020821.3(VPS13C):c.776G>A (p.Trp259Ter)	Pathogenic
1450734	NM_020821.3(VPS13C):c.2029G>T (p.Gly677Ter)	Pathogenic
1471016	NM_020821.3(VPS13C):c.9262del (p.Thr3088fs)	Pathogenic
1475475	NM_020821.3(VPS13C):c.1699C>T (p.Arg567Ter)	Pathogenic
1701261	NM_020821.3(VPS13C):c.3196_3197delinsT (p.Asn1066fs)	Pathogenic
1937487	NM_020821.3(VPS13C):c.1114C>T (p.Arg372Ter)	Pathogenic
1941006	NM_020821.3(VPS13C):c.349C>T (p.Arg117Ter)	Pathogenic
1964483	NM_020821.3(VPS13C):c.6433C>T (p.Gln2145Ter)	Pathogenic
1974513	NM_020821.3(VPS13C):c.6539_6542del (p.Phe2180fs)	Pathogenic
1977819	NM_020821.3(VPS13C):c.6809C>G (p.Ser2270Ter)	Pathogenic
2006931	NM_020821.3(VPS13C):c.9850_9854dup (p.Pro3286fs)	Pathogenic
2006932	NM_020821.3(VPS13C):c.2779C>T (p.Gln927Ter)	Pathogenic
2020191	NM_020821.3(VPS13C):c.615_617del (p.Tyr205_Glu206delinsTer)	Pathogenic
2031092	NM_020821.3(VPS13C):c.6601del (p.Phe2200_Ile2201insTer)	Pathogenic
2039083	NM_020821.3(VPS13C):c.333dup (p.Gln112fs)	Pathogenic
2126582	NM_020821.3(VPS13C):c.5116_5119del (p.Val1706fs)	Pathogenic
222067	NM_020821.3(VPS13C):c.8445+2T>G	Pathogenic
222068	NM_020821.3(VPS13C):c.806_807insCAGA (p.Arg269fs)	Pathogenic
222069	NM_020821.3(VPS13C):c.9568G>T (p.Glu3190Ter)	Pathogenic
222071	NM_020821.3(VPS13C):c.4777del (p.Gln1593fs)	Pathogenic
224604	NM_020821.3(VPS13C):c.802_805dup (p.Arg269fs)	Pathogenic
2413815	NM_020821.3(VPS13C):c.6973C>T (p.Gln2325Ter)	Pathogenic
2662741	NM_020821.3(VPS13C):c.9366del (p.Lys3122fs)	Pathogenic
2724228	NM_020821.3(VPS13C):c.464del (p.Lys155fs)	Pathogenic
2868674	NM_020821.3(VPS13C):c.10756G>T (p.Glu3586Ter)	Pathogenic
2984894	NM_020821.3(VPS13C):c.9175C>T (p.Gln3059Ter)	Pathogenic
2993124	NM_020821.3(VPS13C):c.9769C>T (p.Gln3257Ter)	Pathogenic

SpliceAI

12283 predictions. Top by Δscore:

Variant	Effect	Δscore
15:61868654:TTTA:T	donor_loss	1.0000
15:61868655:TTACC:T	donor_loss	1.0000
15:61868656:TACCT:T	donor_loss	1.0000
15:61868657:AC:A	donor_loss	1.0000
15:61868680:AGATT:A	donor_gain	1.0000
15:61868684:T:TA	donor_gain	1.0000
15:61868769:CTGCC:C	acceptor_gain	1.0000
15:61868772:CC:C	acceptor_gain	1.0000
15:61868773:CC:C	acceptor_gain	1.0000
15:61868773:CCTG:C	acceptor_loss	1.0000
15:61868774:C:CC	acceptor_gain	1.0000
15:61868775:T:A	acceptor_loss	1.0000
15:61868784:C:CT	acceptor_gain	1.0000
15:61868785:A:T	acceptor_gain	1.0000
15:61868787:CAGAG:C	acceptor_gain	1.0000
15:61868788:A:T	acceptor_gain	1.0000
15:61869642:CA:C	acceptor_gain	1.0000
15:61871984:CATA:C	donor_loss	1.0000
15:61871985:ATACC:A	donor_loss	1.0000
15:61871986:TACC:T	donor_loss	1.0000
15:61871987:A:AC	donor_gain	1.0000
15:61871987:A:T	donor_loss	1.0000
15:61871988:C:CA	donor_loss	1.0000
15:61871988:C:CC	donor_gain	1.0000
15:61872031:CTCC:C	acceptor_gain	1.0000
15:61872032:TCC:T	acceptor_gain	1.0000
15:61872033:CC:C	acceptor_gain	1.0000
15:61872033:CCC:C	acceptor_gain	1.0000
15:61872033:CCCTG:C	acceptor_loss	1.0000
15:61872034:CC:C	acceptor_gain	1.0000

AlphaMissense

24798 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:61884256:A:G	W3119R	0.999
15:61884256:A:T	W3119R	0.999
15:61873370:A:T	V3485D	0.998
15:62035029:A:G	W71R	0.998
15:62035029:A:T	W71R	0.998
15:61869527:G:T	A3574D	0.997
15:61911958:A:T	V2866D	0.997
15:61940717:C:G	R1844P	0.997
15:62060295:A:G	L27P	0.997
15:62060343:A:G	L11P	0.997
15:61873401:C:G	A3475P	0.996
15:61884254:C:A	W3119C	0.996
15:61884254:C:G	W3119C	0.996
15:61913392:A:C	S2823R	0.996
15:61913392:A:T	S2823R	0.996
15:61913394:T:G	S2823R	0.996
15:61915750:G:C	N2776K	0.996
15:61915750:G:T	N2776K	0.996
15:61929619:A:C	F2056L	0.996
15:61929619:A:T	F2056L	0.996
15:61929621:A:G	F2056L	0.996
15:61931129:A:G	L2000P	0.996
15:62035034:A:G	I69T	0.996
15:62035040:A:G	L67S	0.996
15:62044234:A:G	L41P	0.996
15:61869528:C:G	A3574P	0.995
15:61869557:G:T	A3564D	0.995
15:61874893:A:G	L3466P	0.995
15:61910293:A:G	W2910R	0.995
15:61910293:A:T	W2910R	0.995

dbSNP variants (sampled 300 via entrez): RS1000043458 (15:62015415 A>G), RS1000053034 (15:61939471 T>C), RS1000069853 (15:62023593 T>C,G), RS1000092269 (15:61865535 T>C), RS1000096149 (15:61914318 C>A), RS1000105224 (15:61856486 G>A,C), RS1000121290 (15:61987968 C>A), RS1000123168 (15:62023242 A>C), RS1000136395 (15:61856184 A>G), RS1000149931 (15:61903017 C>A,T), RS1000152333 (15:61987712 T>G), RS1000162901 (15:61944920 T>C), RS1000186226 (15:61899703 T>A), RS1000197405 (15:62029250 T>C), RS1000209198 (15:61983107 C>T)

Disease associations

OMIM: gene MIM:608879 | disease phenotypes: MIM:616840, MIM:168600

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive early-onset Parkinson disease 23	Strong	Autosomal recessive
young-onset Parkinson disease	Supportive	Autosomal recessive
schizophrenia	No Known Disease Relationship	Unknown

Mondo (5): autosomal recessive early-onset Parkinson disease 23 (MONDO:0014796), Parkinson disease (MONDO:0005180), young-onset Parkinson disease (MONDO:0017279), thyroid hemiagenesis (MONDO:0019860), schizophrenia (MONDO:0005090)

Orphanet (3): Young-onset Parkinson disease (Orphanet:2828), Thyroid hemiagenesis (Orphanet:95719), NON RARE IN EUROPE: Parkinson disease (Orphanet:319705)

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000551	Color vision defect
HP:0000651	Diplopia
HP:0000713	Agitation
HP:0000716	Depression
HP:0000726	Dementia
HP:0000727	Frontal lobe dementia
HP:0000736	Short attention span
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0001257	Spasticity
HP:0001268	Mental deterioration
HP:0001289	Confusion
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001350	Slurred speech
HP:0002014	Diarrhea
HP:0002015	Dysphagia
HP:0002018	Nausea
HP:0002019	Constipation
HP:0002063	Rigidity
HP:0002067	Bradykinesia
HP:0002120	Cerebral cortical atrophy
HP:0002141	Gait imbalance
HP:0002172	Postural instability
HP:0002185	Neurofibrillary tangles
HP:0002304	Akinesia

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST000569_3	Two-hour glucose challenge	1.000000e-07
GCST001212_4	Proinsulin levels	4.000000e-20
GCST001527_24	Fasting blood glucose (BMI interaction)	6.000000e-12
GCST002544_3	Parkinson’s disease	1.000000e-11
GCST003985_17	Breast size	2.000000e-07
GCST004902_9	Parkinson’s disease	4.000000e-14
GCST004904_178	Body mass index	4.000000e-10
GCST004904_4	Body mass index	8.000000e-10
GCST004946_139	Schizophrenia	8.000000e-13
GCST005186_33	Fasting blood glucose	1.000000e-10
GCST005212_29	Asthma	1.000000e-09
GCST006065_41	Glaucoma (primary open-angle)	5.000000e-09
GCST006394_99	Intraocular pressure	8.000000e-18
GCST006412_90	Intraocular pressure	4.000000e-18
GCST006803_74	Schizophrenia	3.000000e-09
GCST006862_16	Asthma	8.000000e-11
GCST007994_14	Asthma (age of onset)	5.000000e-06
GCST007995_44	Asthma (childhood onset)	3.000000e-15
GCST008109_4	Fasting blood proinsulin levels	7.000000e-18
GCST009186_11	Insular cortex volume	4.000000e-06
GCST009325_19	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	6.000000e-18
GCST009725_14	Intraocular pressure	7.000000e-18
GCST010242_222	HDL cholesterol levels	8.000000e-09
GCST010244_292	Triglyceride levels	2.000000e-12
GCST011395_2	Tuberculosis susceptibility in HIV infection	2.000000e-06
GCST90011770_70	Glaucoma (primary open-angle)	3.000000e-15
GCST90014268_31	Cataracts	8.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004307	glucose tolerance test
EFO:0004467	insulin measurement
EFO:0004340	body mass index
EFO:0004695	intraocular pressure measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D010300	Parkinson Disease	C10.228.140.079.862.500; C10.228.662.600.400; C10.574.928.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	3
Valproic Acid	increases expression, affects expression, decreases expression	3
bisphenol A	decreases expression, increases methylation	2
Arsenic	increases abundance, affects methylation, decreases expression	2
Formaldehyde	decreases expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
2,4,6-tribromophenol	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	increases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression, increases abundance	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
mercuric bromide	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
torcetrapib	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol S	increases expression	1

Cellosaurus cell lines

16 cell lines: 7 embryonic stem cell, 6 cancer cell line, 2 induced pluripotent stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D3YF	WIBRe001-A-60	Embryonic stem cell	Female
CVCL_D3YG	WIBRe001-A-59	Embryonic stem cell	Female
CVCL_D3YH	WIBRe001-A-58	Embryonic stem cell	Female
CVCL_D3YI	WIBRe001-A-57	Embryonic stem cell	Female
CVCL_D3YJ	WIBRe001-A-56	Embryonic stem cell	Female
CVCL_D3YK	WIBRe001-A-55	Embryonic stem cell	Female
CVCL_D3YL	WIBRe001-A-54	Embryonic stem cell	Female
CVCL_E4TQ	KOLF2.1J VPS13C 103.8kbdel DEL/DEL	Induced pluripotent stem cell	Male
CVCL_E6IP	A549 VPS13C KO	Cancer cell line	Male
CVCL_E6IQ	Hela M VPS13C-KO clone 1	Cancer cell line	Female

Clinical trials (associated diseases)

600 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety