autosomal recessive early-onset Parkinson disease 23

Summary

autosomal recessive early-onset Parkinson disease 23 (MONDO:0014796) is a disease caused by VPS13C (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: VPS13C (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 59

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive early-onset Parkinson disease 23
Mondo ID	MONDO:0014796
OMIM	616840
DOID	DOID:0060896
UMLS	C4225186
MedGen	896607
GARD	0018610
Is cancer (heuristic)	no

Also known as: autosomal recessive early-onset Parkinson disease 23 · autosomal recessive early-onset Parksinson disease type 23 · PARK23 · Parkinson disease 23, autosomal recessive early-onset · Parkinson disease 23, autosomal recessive, early onset · VPS13C young-onset Parkinson disease · young-onset Parkinson disease caused by mutation in VPS13C

Data availability: 59 ClinVar variants · 3 GenCC gene-disease records · 9 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › basal ganglia disorder › parkinsonian disorder › Parkinson disease › young-onset Parkinson disease › autosomal recessive early-onset Parkinson disease 23

Related subtypes (8): juvenile-onset Parkinson disease, Parkinson disease 12, autosomal recessive juvenile Parkinson disease 2, Parkinson disease 3, autosomal dominant, autosomal recessive early-onset Parkinson disease 6, autosomal recessive early-onset Parkinson disease 7, Parkinson disease 10, early-onset Parkinson disease 20

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

59 retrieved; paginated sample, class counts are floors:

19 uncertain significance, 14 likely pathogenic, 10 pathogenic, 9 benign, 5 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323753	NM_020821.3(VPS13C):c.10060G>T (p.Glu3354Ter)	VPS13C	Pathogenic	criteria provided, multiple submitters, no conflicts
1323755	NM_020821.3(VPS13C):c.5842_5843insATGA (p.Ile1948fs)	VPS13C	Pathogenic	criteria provided, single submitter
1325345	NM_020821.3(VPS13C):c.8806C>T (p.Arg2936Ter)	VPS13C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
222067	NM_020821.3(VPS13C):c.8445+2T>G	VPS13C	Pathogenic	criteria provided, single submitter
222069	NM_020821.3(VPS13C):c.9568G>T (p.Glu3190Ter)	VPS13C	Pathogenic	criteria provided, single submitter
222070	NM_020821.3(VPS13C):c.4165G>C (p.Gly1389Arg)	VPS13C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
222071	NM_020821.3(VPS13C):c.4777del (p.Gln1593fs)	VPS13C	Pathogenic	criteria provided, single submitter
224604	NM_020821.3(VPS13C):c.802_805dup (p.Arg269fs)	VPS13C	Pathogenic	no assertion criteria provided
2434582	NM_020821.3(VPS13C):c.1193_1194del (p.Ile398fs)	VPS13C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3238850	NM_020821.3(VPS13C):c.3849C>A (p.Tyr1283Ter)	VPS13C	Pathogenic	criteria provided, single submitter
3902376	NM_020821.3(VPS13C):c.8972_8975del (p.Lys2991fs)	VPS13C	Pathogenic	criteria provided, single submitter
4535859	NM_020821.3(VPS13C):c.9152G>A (p.Trp3051Ter)	VPS13C	Pathogenic	criteria provided, single submitter
4848655	NM_020821.3(VPS13C):c.7939G>T (p.Glu2647Ter)	VPS13C	Pathogenic	criteria provided, single submitter
870544	NM_020821.3(VPS13C):c.10954C>T (p.Arg3652Ter)	VPS13C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
982938	NM_020821.3(VPS13C):c.1111C>T (p.Arg371Ter)	VPS13C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1030583	NM_020821.3(VPS13C):c.1483+1G>A	VPS13C	Likely pathogenic	criteria provided, single submitter
1325346	NM_020821.3(VPS13C):c.10786_10792del (p.Pro3596fs)	VPS13C	Likely pathogenic	criteria provided, single submitter
2585188	NM_020821.3(VPS13C):c.10576C>T (p.Arg3526Ter)	VPS13C	Likely pathogenic	criteria provided, single submitter
2690778	NM_020821.3(VPS13C):c.9481G>T (p.Glu3161Ter)	VPS13C	Likely pathogenic	criteria provided, single submitter
2880695	NM_020821.3(VPS13C):c.5868+1G>A	VPS13C	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3064720	NM_020821.3(VPS13C):c.9019C>T (p.Arg3007Ter)	VPS13C	Likely pathogenic	criteria provided, single submitter
3065269	NM_020821.3(VPS13C):c.5756-1G>T	VPS13C	Likely pathogenic	criteria provided, single submitter
3068084	NM_020821.3(VPS13C):c.10414+1G>A	VPS13C	Likely pathogenic	criteria provided, single submitter
3382142	NM_020821.3(VPS13C):c.6726del (p.Lys2242fs)	VPS13C	Likely pathogenic	criteria provided, single submitter
3393072	NM_020821.3(VPS13C):c.9562C>T (p.Gln3188Ter)	VPS13C	Likely pathogenic	criteria provided, single submitter
3629695	NM_020821.3(VPS13C):c.385+1G>T	VPS13C	Likely pathogenic	criteria provided, single submitter
4076299	NM_020821.3(VPS13C):c.6053_6056del (p.Lys2018fs)	VPS13C	Likely pathogenic	criteria provided, single submitter
4848396	NM_020821.3(VPS13C):c.385+1G>A	VPS13C	Likely pathogenic	criteria provided, single submitter
4849313	NM_020821.3(VPS13C):c.9551T>A (p.Leu3184Ter)	VPS13C	Likely pathogenic	criteria provided, single submitter
547944	NM_020821.3(VPS13C):c.387C>T (p.Gly129=)	VPS13C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
VPS13C	Strong	Autosomal recessive	autosomal recessive early-onset Parkinson disease 23	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
VPS13C	Orphanet:2828	Young-onset Parkinson disease

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
VPS13C	HGNC:23594	ENSG00000129003	Q709C8	Intermembrane lipid transfer protein VPS13C	gencc,clinvar
VWA8	HGNC:29071	ENSG00000102763	A3KMH1	von Willebrand factor A domain-containing protein 8	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
VPS13C	Intermembrane lipid transfer protein VPS13C	Mediates the transfer of lipids between membranes at organelle contact sites.
VWA8	von Willebrand factor A domain-containing protein 8	Exhibits ATPase activity in vitro.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
VPS13C	Other/Unknown	no		VPS13_VAB, VPS13, VPS13_N
VWA8	Other/Unknown	no		VWF_A, AAA+_ATPase, ATPase_dyneun-rel_AAA

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
epithelium of nasopharynx	1
upper leg skin	1
left ventricle myocardium	1
quadriceps femoris	1
vastus lateralis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VPS13C	291	ubiquitous	marker	calcaneal tendon, upper leg skin, epithelium of nasopharynx
VWA8	285	ubiquitous	marker	vastus lateralis, left ventricle myocardium, quadriceps femoris

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
VPS13C	2,056
VWA8	1,940

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
VWA8	A3KMH1	79.24
VPS13C	Q709C8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of type 2 mitophagy	1	8426.0×	8e-04	VPS13C
protein retention in Golgi apparatus	1	3370.4×	0.001	VPS13C
protein targeting to vacuole	1	1296.3×	0.002	VPS13C
Golgi to endosome transport	1	1053.2×	0.002	VPS13C
lipid transport	1	263.3×	0.005	VPS13C
response to insulin	1	230.8×	0.005	VPS13C
mitochondrion organization	1	151.8×	0.007	VPS13C

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
VPS13C	0	0
VWA8	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	VPS13C, VWA8

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
VPS13C	0	—
VWA8	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.