VPS13A

Summary

VPS13A (vacuolar protein sorting 13 homolog A, HGNC:1908) is a protein-coding gene on chromosome 9q21.2, encoding Intermembrane lipid transfer protein VPS13A (Q96RL7). Mediates the transfer of lipids between membranes at organelle contact sites.

The protein encoded by this gene may control steps in the cycling of proteins through the trans-Golgi network to endosomes, lysosomes and the plasma membrane. Mutations in this gene cause the autosomal recessive disorder, chorea-acanthocytosis. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 23230 — RefSeq curated summary.

At a glance

• Gene–disease (curated): VPS13A-related neurodegenerative disease (Definitive, GenCC)
• GWAS associations: 11
• Clinical variants (ClinVar): 3,945 total — 262 pathogenic, 214 likely-pathogenic
• Phenotypes (HPO): 106
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_033305

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1908
Approved symbol	VPS13A
Name	vacuolar protein sorting 13 homolog A
Location	9q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0986, BLTP5A
Ensembl gene	ENSG00000197969
Ensembl biotype	protein_coding
OMIM	605978
Entrez	23230

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000355766, ENST00000360280, ENST00000376636, ENST00000376646, ENST00000419472, ENST00000423463, ENST00000467124, ENST00000471439, ENST00000484581, ENST00000493341, ENST00000539950, ENST00000643348, ENST00000645632

RefSeq mRNA: 4 — MANE Select: NM_033305 NM_001018037, NM_001018038, NM_015186, NM_033305

CCDS: CCDS47983, CCDS55321, CCDS6655, CCDS6656

Canonical transcript exons

ENST00000360280 — 72 exons

Exon	Start	End
ENSE00000707969	77319572	77319673
ENSE00000708020	77321169	77321327
ENSE00000708046	77321491	77321746
ENSE00000708066	77323067	77323227
ENSE00000708138	77337255	77337537
ENSE00000708158	77339516	77339911
ENSE00000708190	77344153	77344281
ENSE00000708224	77351317	77351446
ENSE00000708298	77356714	77356867
ENSE00000708339	77359333	77359402
ENSE00000708354	77360536	77360641
ENSE00000708378	77365460	77365573
ENSE00000708397	77368055	77368136
ENSE00000708458	77370257	77370332
ENSE00000803886	77332010	77332113
ENSE00000803888	77340178	77340282
ENSE00000803889	77340404	77340550
ENSE00000803891	77345009	77345142
ENSE00000803893	77353409	77353641
ENSE00000803895	77357692	77357838
ENSE00000803896	77358357	77358438
ENSE00000803900	77366727	77366872
ENSE00000803902	77369299	77369412
ENSE00000803904	77370415	77370578
ENSE00000803908	77371026	77371149
ENSE00000803909	77381976	77382087
ENSE00000803911	77405864	77405987
ENSE00000803912	77407533	77407607
ENSE00001024087	77213234	77213314
ENSE00001024094	77220277	77220383
ENSE00001024102	77276065	77276221
ENSE00001024116	77201365	77201407
ENSE00001024126	77226466	77226598
ENSE00001024128	77214329	77214386
ENSE00001024142	77228122	77228264
ENSE00001024153	77212969	77213028
ENSE00001024156	77250097	77250229
ENSE00001024168	77238272	77238386
ENSE00001024170	77273280	77273364
ENSE00001024173	77225926	77225988
ENSE00001171765	77275498	77275652
ENSE00001171781	77260086	77260224
ENSE00001171789	77252235	77252352
ENSE00001171806	77247259	77247395
ENSE00001171829	77238002	77238191
ENSE00001171842	77227391	77227485
ENSE00001171863	77221185	77221356
ENSE00001171880	77219954	77220081
ENSE00001171911	77209423	77209532
ENSE00001171919	77205978	77206079
ENSE00001171927	77205313	77205408
ENSE00001171942	77199945	77199988
ENSE00001388252	77370890	77370935
ENSE00001833389	77177534	77177804
ENSE00003466654	77295542	77295846
ENSE00003471630	77282121	77282274
ENSE00003484318	77317606	77317698
ENSE00003492193	77403236	77403321
ENSE00003501421	77283547	77283650
ENSE00003507279	77314495	77314664
ENSE00003515053	77318235	77318591
ENSE00003516104	77315253	77315470
ENSE00003517376	77283355	77283471
ENSE00003521243	77313992	77314119
ENSE00003529754	77293341	77293508
ENSE00003541744	77307945	77308098
ENSE00003562120	77280159	77280238
ENSE00003573182	77210616	77210675
ENSE00003608521	77302915	77303062
ENSE00003637866	77281867	77281926
ENSE00003686011	77316174	77316406
ENSE00003843468	77415956	77421537

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 94.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.3760 / max 462.9354, expressed in 1808 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97009	24.4874	1802
97010	1.7810	935
97008	0.0895	25
97014	0.0110	2
97015	0.0071	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	94.15	gold quality
biceps brachii	UBERON:0001507	93.15	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.66	gold quality
calcaneal tendon	UBERON:0003701	92.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.11	gold quality
jejunum	UBERON:0002115	91.78	gold quality
left coronary artery	UBERON:0001626	91.24	gold quality
adrenal tissue	UBERON:0018303	91.14	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.99	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.88	gold quality
hair follicle	UBERON:0002073	90.87	gold quality
mucosa of stomach	UBERON:0001199	90.50	gold quality
rectum	UBERON:0001052	90.47	gold quality
small intestine	UBERON:0002108	90.42	gold quality
lower esophagus mucosa	UBERON:0035834	90.33	gold quality
coronary artery	UBERON:0001621	90.27	gold quality
body of pancreas	UBERON:0001150	90.20	gold quality
popliteal artery	UBERON:0002250	90.12	gold quality
tibial artery	UBERON:0007610	90.12	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.10	gold quality
transverse colon	UBERON:0001157	90.04	gold quality
lower esophagus	UBERON:0013473	90.01	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.99	gold quality
right atrium auricular region	UBERON:0006631	89.43	gold quality
right coronary artery	UBERON:0001625	89.42	gold quality
cardiac atrium	UBERON:0002081	89.32	gold quality
endothelial cell	CL:0000115	89.23	gold quality
aorta	UBERON:0000947	89.22	gold quality
duodenum	UBERON:0002114	89.12	gold quality
body of stomach	UBERON:0001161	89.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting VPS13A, 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-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-4672	99.50	71.58	2893

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 38)

• Founder mutation and single-nucleotid epolymorphisms in chorea-acanthocytosis in French-Canadians. (PMID:15918062)
• The index patient was homozygous for a 3889C>T nonsense mutation in the VPS13A gene and presented with a typical ChAc phenotype. (PMID:17673232)
• A Mexican family, two sister, after mutation screening of the VPS13A gene revealed homozygosity for the frameshift mutation c.3556_3557dupAC in exon 33. (PMID:17998451)
• identified 36 pathogenic mutations of VPS13A, 20 of which were previously unreported, including two novel copy number variations (PMID:21598378)
• Frameshift mutations of VPS genes and losses of expression of Vps13A and Vps35 proteins are common in gastric cancers and colorectal cancers with high microsatellite instability. (PMID:21733561)
• A mutation was identified in the VPS13A gene, responsible for autosomal recessive chorea-acanthocytosis. (PMID:21987550)
• This study demonistrated that neuroacanthocytosis disorders has heterozygotes for mutations in the VPS13A gene. (PMID:22038564)
• Results reveal chorein as a novel powerful regulator of cytoskeletal architecture and cell survival, thus explaining erythrocyte misshape and possibly neurodegeneration in chorea-acanthocytosis. (PMID:22227296)
• these results suggest that chorein is involved in exocytosis of dense-core vesicles. (PMID:22366033)
• Data indicate functions of chorein, i.e., regulation of secretion and aggregation of blood platelets. (PMID:23568775)
• Discovery of new mutations may clarify the pathogenic roles of chorein in chorea-acanthocytosis as well as in the retina (PMID:23746940)
• chorein interacts with beta-adducin and beta-actin. (PMID:24129186)
• Chorein is expressed in various cancer cells. In cells with high chorein expression levels chorein silencing promotes apoptotic cell death, an effect paralleled by down-regulation of PI-3K activity and BCL-2/Bax expression ratio. (PMID:25871399)
• VPS13A-depleted cells showed accumulation of autophagic markers and impaired autophagic flux (PMID:25996471)
• Defective chorein is accompanied by significant structural disorganization of all cytoskeletal structures. (PMID:26316086)
• Patients with chorea-acanthocytosis carrying a VPS13A mutation present with focal, treatment-resistant seizures. (PMID:26813249)
• Chorein is a stimulator of Orai1 expression and thus of store operated Ca2+ entry. (PMID:27960157)
• Expression of cancer-specific glycan epitopes represents an excellent opportunity for diagnostics and potentially specific detection of tumors. Here, we report four proteins (LIFR, CE350, VP13A, HPT) found in sera from pancreatic cancer patients carrying aberrant glycan structures as compared to those of controls. (PMID:28244758)
• These results suggest that PI3P regulates the functioning of Vps13, both in protein trafficking and actin cytoskeleton organization. Attenuation of PI3P-binding ability in the mutant hVps13A protein may be one of the reasons for its mislocalization and disrupted function in cells of patients suffering from chorea-acanthocytosis . (PMID:28334785)
• Even though these are long noted disease conditions, we still know only little on the underlying disease mechanisms. The current review focuses upon Chorea-Acanthocytosis as the core entity of Neuroacanthocytosis syndromes caused by mutations in the VPS13A gene (PMID:29253590)
• New pathogenic mutation of chorea-acanthocytosis.", trans “Nueva mutacion patogenica de corea-acantocitosis. (PMID:29752031)
• 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)
• VPS13A localizes at the interface between mitochondria-endosomes and mitochondria-endoplasmic reticulum and that the presence of membrane contact sites is altered in the absence of VPS13A. (PMID:30709847)
• We demonstrate that VPS13A is a peripheral membrane protein, associated with mitochondria, the endoplasmic reticulum and lipid droplets. VPS13A is localized at sites where the endoplasmic reticulum and mitochondria are in close contact (PMID:30741634)
• A novel nonsense p.Gln113* mutation in VPS13A identified by whole-exome sequencing, which caused Choreoacanthocytosis in a Moroccan family. (PMID:32131761)
• Combined Dendritic and Axonal Deterioration Are Responsible for Motoneuronopathy in Patient-Derived Neuronal Cell Models of Chorea-Acanthocytosis. (PMID:32151030)
• The binding of the APT1 domains to phosphoinositides is regulated by metal ions in vitro. (PMID:32407779)
• XK is a partner for VPS13A: a molecular link between Chorea-Acanthocytosis and McLeod Syndrome. (PMID:32845802)
• TBC1D1 interacting proteins, VPS13A and VPS13C, regulate GLUT4 homeostasis in C2C12 myotubes. (PMID:33087848)
• Translational study of the whole transcriptome in rats and genetic polymorphisms in humans identifies LRP1B and VPS13A as key genes involved in tolerance to cocaine-induced motor disturbances. (PMID:33159041)
• Structural and biochemical insights into lipid transport by VPS13 proteins. (PMID:35357422)
• Interaction between VPS13A and the XK scramblase is important for VPS13A function in humans. (PMID:35950506)
• A partnership between the lipid scramblase XK and the lipid transfer protein VPS13A at the plasma membrane. (PMID:35994651)
• The association of lipid transfer protein VPS13A with endosomes is mediated by sorting nexin SNX5. (PMID:36977596)
• Exome sequencing of choreoacanthocytosis reveals novel mutations in VPS13A and co-mutation in modifier gene(s). (PMID:37209156)
• An Autopsy Series of Seven Cases of VPS13A Disease (Chorea-Acanthocytosis). (PMID:37670483)
• Chorein sensitive microtubule organization in tumor cells. (PMID:37744224)
• Clinical Features and Novel Pathogenic Variants of Chinese Patients With McLeod Syndrome and Chorea-Acanthocytosis. (PMID:39324427)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	vps13a	ENSDARG00000039225
mus_musculus	Vps13a	ENSMUSG00000046230
rattus_norvegicus	Vps13a	ENSRNOG00000025539
drosophila_melanogaster	Vps13	FBGN0033194
caenorhabditis_elegans	vps-13	WBGENE00011629

Paralogs (2): VPS13D (ENSG00000048707), VPS13C (ENSG00000129003)

Protein

Protein identifiers

Intermembrane lipid transfer protein VPS13A — Q96RL7 (reviewed: Q96RL7)

Alternative names: Chorea-acanthocytosis protein, Chorein, Vacuolar protein sorting-associated protein 13A

All UniProt accessions (4): H0Y7P8, H0YF78, H0YG53, Q96RL7

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the transfer of lipids between membranes at organelle contact sites. Binds phospholipids. Required for the formation or stabilization of ER-mitochondria contact sites which enable transfer of lipids between the ER and mitochondria. Negatively regulates lipid droplet size and motility. Required for efficient lysosomal protein degradation.

Subunit / interactions. Interacts (via FFAT motif) with VAPA and VAPB. Interacts with RAB7A. Interacts with XK.

Subcellular location. Mitochondrion outer membrane. Endoplasmic reticulum membrane. Endosome membrane. Lysosome membrane. Lipid droplet. Golgi apparatus. Cytoplasmic vesicle. Secretory vesicle. Neuronal dense core vesicle.

Tissue specificity. Expressed in red blood cells (at protein level). Widely expressed, with high expression in brain, heart, skeletal muscle and kidney.

Disease relevance. Choreoacanthocytosis (CHAC) [MIM:200150] An autosomal recessive neurodegenerative disorder characterized by the gradual onset of hyperkinetic movements and abnormal erythrocyte morphology. Basal ganglia atrophy in the brain is a pathological feature of the disease. Other clinical symptoms include psychiatric features, epilepsy, peripheral neuropathy, myopathy and oral self-mutilation. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal part (3058-3174) is involved in phospholipid binding, including phosphatidylinositol 4,5-bisphosphate. The FFAT motif is required for interaction with VAPA and VAPB and its localization to the endoplasmic reticulum.

Similarity. Belongs to the VPS13 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96RL7-1	1, A	yes
Q96RL7-2	2, B
Q96RL7-3	3, Chorein 2A
Q96RL7-4	4, Chorein 1D

RefSeq proteins (4): NP_001018047, NP_001018048, NP_056001, NP_150648* (*=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 (64 total): sequence variant 33, repeat 10, sequence conflict 7, splice variant 4, domain 2, region of interest 2, modified residue 2, mutagenesis site 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q96RL7 — 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 (2): 839, 1416

Mutagenesis-validated functional residues (2):

Position	Phenotype
842	reduced interaction with vapa.
843–844	abnormal localization to the cytosol.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 429 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_BEHAVIOR, GOBP_MYELOID_CELL_HOMEOSTASIS, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_INFLAMMATORY_RESPONSE, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, CMYB_01, GOBP_ADULT_BEHAVIOR, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_ERYTHROCYTE_HOMEOSTASIS, GOBP_GROWTH, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS

GO Biological Process (30): protein targeting to vacuole (GO:0006623), lipid transport (GO:0006869), Golgi to endosome transport (GO:0006895), autophagy (GO:0006914), intracellular protein localization (GO:0008104), adult locomotory behavior (GO:0008344), protein secretion (GO:0009306), gene expression (GO:0010467), microglia differentiation (GO:0014004), erythrocyte differentiation (GO:0030218), flagellated sperm motility (GO:0030317), sperm mitochondrion organization (GO:0030382), brain-derived neurotrophic factor receptor signaling pathway (GO:0031547), social behavior (GO:0035176), multicellular organism growth (GO:0035264), exploration behavior (GO:0035640), protein retention in Golgi apparatus (GO:0045053), neuromuscular process controlling balance (GO:0050885), long-term synaptic depression (GO:0060292), motor behavior (GO:0061744), cellular response to osmotic stress (GO:0071470), response to environmental enrichment (GO:0090648), neuron projection arborization (GO:0140058), neuroinflammatory response (GO:0150076), lysosomal protein catabolic process (GO:1905146), cell morphogenesis (GO:0000902), nervous system development (GO:0007399), locomotory behavior (GO:0007626), regulation of synaptic plasticity (GO:0048167), neuromuscular process (GO:0050905)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (21): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), lysosomal membrane (GO:0005765), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), lipid droplet (GO:0005811), cytosol (GO:0005829), endosome membrane (GO:0010008), mitochondrial membrane (GO:0031966), neuron projection (GO:0043005), neuronal cell body (GO:0043025), mitochondria-associated endoplasmic reticulum membrane contact site (GO:0044233), sperm midpiece (GO:0097225), neuronal dense core vesicle lumen (GO:0099013), lysosome (GO:0005764), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), dense core granule (GO:0031045), cytoplasmic vesicle (GO:0031410), neuronal dense core vesicle (GO:0098992)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	5
behavior	3
intracellular membrane-bounded organelle	3
endomembrane system	3
cellular anatomical structure	3
organelle membrane	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
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
macromolecule localization	1
locomotory behavior	1
adult behavior	1
protein transport	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
macromolecule biosynthetic process	1
central nervous system development	1
glial cell differentiation	1
macrophage differentiation	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
mitochondrion organization	1
cell surface receptor protein tyrosine kinase signaling pathway	1
biological process involved in intraspecies interaction between organisms	1
multicellular organismal process	1
developmental growth	1

Protein interactions and networks

STRING

1864 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VPS13A	XK	P51811	952
VPS13A	JPH3	Q8WXH2	827
VPS13A	KEL	P23276	728
VPS13A	VAPA	Q9P0L0	700
VPS13A	STS	P08842	647
VPS13A	PDZD8	Q8NEN9	643
VPS13A	ADD2	P35612	603
VPS13A	PHC1	P78364	601
VPS13A	CHAT	P28329	599
VPS13A	ATG2A	Q2TAZ0	591
VPS13A	MFN2	O95140	572
VPS13A	RAB7A	P51149	540
VPS13A	VPS13B	Q7Z7G8	532
VPS13A	PANK2	Q9BZ23	523
VPS13A	HTT	P42858	518

IntAct

56 interactions, top by confidence:

A	B	Type	Score
EGFR	CTNND1	psi-mi:“MI:0914”(association)	0.750
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
ARPC5	ARPC3	psi-mi:“MI:0914”(association)	0.730
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
XKRX	FAM234B	psi-mi:“MI:0914”(association)	0.530
TMEM31	PSMD11	psi-mi:“MI:0914”(association)	0.530
RNF19B	PIK3R2	psi-mi:“MI:0914”(association)	0.530
PPIAL4G	ACTB	psi-mi:“MI:0914”(association)	0.530
ABL1	VPS13A	psi-mi:“MI:0915”(physical association)	0.400
FYN	VPS13A	psi-mi:“MI:0915”(physical association)	0.400
VPS13A	GRB2	psi-mi:“MI:0915”(physical association)	0.400
VPS13A	NCK1	psi-mi:“MI:0915”(physical association)	0.400
VPS13A	PIK3R1	psi-mi:“MI:0915”(physical association)	0.400
	AP3B1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
	DENND11	psi-mi:“MI:0914”(association)	0.350
M	DENND11	psi-mi:“MI:0914”(association)	0.350
CALM1	MYO1C	psi-mi:“MI:0914”(association)	0.350
CALM2	MYO1C	psi-mi:“MI:0914”(association)	0.350

BioGRID (172): VPS13A (Affinity Capture-MS), VPS13A (Affinity Capture-MS), VPS13A (Affinity Capture-MS), VPS13A (Affinity Capture-MS), VPS13A (Affinity Capture-MS), VPS13A (Affinity Capture-MS), VPS13A (Co-fractionation), VPS13A (Co-fractionation), VPS13A (Co-fractionation), VPS13A (Affinity Capture-MS), VPS13A (Affinity Capture-MS), VPS13A (Affinity Capture-MS), VPS13A (Proximity Label-MS), VPS13A (Affinity Capture-MS), VPS13A (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: A0JNW5, A2RSJ4, Q08D51, Q21480, Q54KX3, Q6NRZ1, Q7Z7G8, Q80TY5, Q96RL7, A1Z713, Q54LN2, Q54PG5, Q5H8C4, Q86K84, Q9BGZ0, Q9VU08, A7E300, B9VTT2, O42926, P30337, P42331, P52757, P81128, P83509, P87319, P97393, Q03070, Q07878, Q13017, Q54E35, Q54FF4, Q54J98, Q54WY8, Q54XE8, Q55DW9, Q55FG3, Q6NU25, Q74ZH7, Q7Z5H3, Q80XD1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 75 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
Regulation of signaling by CBL	5	42.8×	7e-06
Parasite infection	6	35.8×	2e-06
Leishmania phagocytosis	6	35.8×	2e-06
RHO GTPases Activate WASPs and WAVEs	6	32.8×	2e-06
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	5	30.8×	3e-05
Fcgamma receptor (FCGR) dependent phagocytosis	6	28.8×	5e-06
FCGR3A-mediated phagocytosis	8	25.8×	5e-07
Leishmania infection	8	22.5×	5e-07

GO biological processes:

GO term	Partners	Fold	FDR
response to endoplasmic reticulum stress	5	12.3×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

3945 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	262
Likely pathogenic	214
Uncertain significance	908
Likely benign	2078
Benign	239

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1028512	NM_033305.3(VPS13A):c.2326C>T (p.Arg776Ter)	Pathogenic
1068730	NC_000009.11:g.(?79982961)(79999609_?)del	Pathogenic
1069532	NM_033305.3(VPS13A):c.2336dup (p.Asp779fs)	Pathogenic
1070001	NM_033305.3(VPS13A):c.1881dup (p.Arg628fs)	Pathogenic
1070414	NM_033305.3(VPS13A):c.7005G>A (p.Trp2335Ter)	Pathogenic
1070545	NM_033305.3(VPS13A):c.5024dup (p.Glu1677fs)	Pathogenic
1070805	NM_033305.3(VPS13A):c.8301del (p.Glu2767fs)	Pathogenic
1070929	NM_033305.3(VPS13A):c.3232G>T (p.Glu1078Ter)	Pathogenic
1072581	NM_033305.3(VPS13A):c.9429_9432del (p.Arg3143fs)	Pathogenic
1073143	NM_033305.3(VPS13A):c.6392C>A (p.Ser2131Ter)	Pathogenic
1073165	NM_033305.3(VPS13A):c.7154_7155insAGTA (p.Leu2386fs)	Pathogenic
1073239	NM_033305.3(VPS13A):c.3394del (p.Asp1132fs)	Pathogenic
1073386	NM_033305.3(VPS13A):c.1304_1313del (p.Leu434_Trp435insTer)	Pathogenic
1073923	NM_033305.3(VPS13A):c.4284del (p.Glu1429fs)	Pathogenic
1073928	NM_033305.3(VPS13A):c.8939_8942del (p.Thr2980fs)	Pathogenic
1074876	NM_033305.3(VPS13A):c.1313C>G (p.Ser438Ter)	Pathogenic
1075357	NM_033305.3(VPS13A):c.1869del (p.Lys623fs)	Pathogenic
1075838	NM_033305.3(VPS13A):c.72dup (p.Ser25fs)	Pathogenic
1076050	NC_000009.12:g.77337257_77337282del	Pathogenic
1076424	NM_033305.3(VPS13A):c.3481dup (p.Val1161fs)	Pathogenic
1076766	NC_000009.11:g.(?_79851768)_79854605del	Pathogenic
1076767	NC_000009.11:g.(?79952161)(79959207_?)del	Pathogenic
1076960	NM_033305.3(VPS13A):c.78dup (p.Leu27fs)	Pathogenic
1184557	NM_033305.3(VPS13A):c.672_676del (p.Tyr224_Ser226delinsTer)	Pathogenic
1323749	NM_033305.3(VPS13A):c.6367_6374del (p.Tyr2123fs)	Pathogenic
1351938	NM_033305.3(VPS13A):c.2405del (p.Ser802fs)	Pathogenic
1353623	NM_033305.3(VPS13A):c.4969_5011del (p.Ile1657fs)	Pathogenic
1353858	NM_033305.3(VPS13A):c.1596-2A>G	Pathogenic
1359084	NM_033305.3(VPS13A):c.7369dup (p.Arg2457fs)	Pathogenic
1363347	NM_033305.3(VPS13A):c.49dup (p.Asp17fs)	Pathogenic

SpliceAI

10981 predictions. Top by Δscore:

Variant	Effect	Δscore
9:77177802:AAGG:A	donor_loss	1.0000
9:77177803:AGGT:A	donor_loss	1.0000
9:77177804:GGT:G	donor_loss	1.0000
9:77177805:GT:G	donor_loss	1.0000
9:77177806:T:G	donor_loss	1.0000
9:77205972:CTATA:C	acceptor_loss	1.0000
9:77205976:A:AC	acceptor_loss	1.0000
9:77205976:A:AG	acceptor_gain	1.0000
9:77205976:AG:A	acceptor_gain	1.0000
9:77205977:G:GT	acceptor_gain	1.0000
9:77205977:GG:G	acceptor_gain	1.0000
9:77205977:GGA:G	acceptor_gain	1.0000
9:77205977:GGAA:G	acceptor_gain	1.0000
9:77205977:GGAAT:G	acceptor_gain	1.0000
9:77206068:T:TA	donor_gain	1.0000
9:77206069:A:AA	donor_gain	1.0000
9:77206078:AGGT:A	donor_loss	1.0000
9:77206079:GGT:G	donor_loss	1.0000
9:77206080:G:GA	donor_loss	1.0000
9:77206081:T:A	donor_loss	1.0000
9:77209398:A:AG	acceptor_gain	1.0000
9:77209399:A:G	acceptor_gain	1.0000
9:77212963:TTTCA:T	acceptor_loss	1.0000
9:77212964:TTCA:T	acceptor_loss	1.0000
9:77212965:TCA:T	acceptor_loss	1.0000
9:77212966:CA:C	acceptor_loss	1.0000
9:77212967:A:AG	acceptor_gain	1.0000
9:77212967:A:C	acceptor_loss	1.0000
9:77212968:G:GT	acceptor_gain	1.0000
9:77212968:GA:G	acceptor_gain	1.0000

AlphaMissense

21025 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:77356727:T:A	W2556R	1.000
9:77356727:T:C	W2556R	1.000
9:77319602:T:A	W1782R	0.999
9:77319602:T:C	W1782R	0.999
9:77370433:C:A	A2921D	0.999
9:77371122:C:A	A3017D	0.999
9:77405913:T:A	W3109R	0.999
9:77405913:T:C	W3109R	0.999
9:77405971:T:C	L3128S	0.999
9:77302992:G:C	R1297P	0.998
9:77319656:T:A	W1800R	0.998
9:77319656:T:C	W1800R	0.998
9:77340185:T:C	L2261P	0.998
9:77356729:G:C	W2556C	0.998
9:77356729:G:T	W2556C	0.998
9:77370281:T:C	F2898L	0.998
9:77370283:T:A	F2898L	0.998
9:77370283:T:G	F2898L	0.998
9:77370330:T:A	V2914D	0.998
9:77370424:C:A	A2918D	0.998
9:77370432:G:C	A2921P	0.998
9:77370918:T:A	V2979D	0.998
9:77371121:G:C	A3017P	0.998
9:77405915:G:C	W3109C	0.998
9:77405915:G:T	W3109C	0.998
9:77407603:C:A	A3157D	0.998
9:77209519:G:C	R161P	0.997
9:77319604:G:C	W1782C	0.997
9:77319604:G:T	W1782C	0.997
9:77339774:A:C	S2213R	0.997

dbSNP variants (sampled 300 via entrez): RS1000008131 (9:77370675 A>T), RS1000010308 (9:77243374 G>C), RS1000021164 (9:77364531 G>C), RS1000037867 (9:77351037 C>G), RS1000046923 (9:77393874 T>G), RS1000057803 (9:77195716 G>A), RS1000086354 (9:77372164 C>T), RS1000097421 (9:77324349 T>C), RS1000106450 (9:77357217 G>T), RS1000107077 (9:77364364 G>T), RS1000107727 (9:77236141 A>G,T), RS1000113550 (9:77275870 A>C), RS1000132268 (9:77202704 T>C), RS1000134096 (9:77288129 C>T), RS1000156635 (9:77285748 T>C)

Disease associations

OMIM: gene MIM:605978 | disease phenotypes: MIM:200150

GenCC curated gene-disease

Disease	Classification	Inheritance
VPS13A-related neurodegenerative disease	Definitive	Autosomal recessive

Mondo (4): VPS13A-related neurodegenerative disease (MONDO:0008695), vascular dementia (MONDO:0004648), breast ductal adenocarcinoma (MONDO:0005590), congenital nervous system disorder (MONDO:0002320)

Orphanet (1): Choreoacanthocytosis (Orphanet:2388)

HPO phenotypes

106 total (30 of 106 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000496	Abnormality of eye movement
HP:0000514	Slow saccadic eye movements
HP:0000643	Blepharospasm
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000719	Inappropriate behavior
HP:0000722	Compulsive behaviors
HP:0000726	Dementia
HP:0000734	Disinhibition
HP:0000736	Short attention span
HP:0000737	Irritability
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000751	Personality changes
HP:0000752	Hyperactivity
HP:0000763	Sensory neuropathy
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration
HP:0001276	Hypertonia
HP:0001284	Areflexia
HP:0001300	Parkinsonism
HP:0001315	Reduced tendon reflexes
HP:0001332	Dystonia

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST003817_9	Mortality in sepsis	8.000000e-08
GCST004619_167	Reticulocyte fraction of red cells	7.000000e-12
GCST004622_20	Reticulocyte count	4.000000e-12
GCST009090_1	Thoracic aortic calcification levels	9.000000e-08
GCST90002385_383	High light scatter reticulocyte count	8.000000e-16
GCST90002386_426	High light scatter reticulocyte percentage of red cells	1.000000e-15
GCST90002391_242	Mean corpuscular hemoglobin concentration	9.000000e-13
GCST90002396_405	Mean reticulocyte volume	7.000000e-53
GCST90002397_682	Mean spheric corpuscular volume	3.000000e-54
GCST90002405_459	Reticulocyte count	4.000000e-28
GCST90002406_324	Reticulocyte fraction of red cells	2.000000e-27

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004352	mortality
EFO:0007986	reticulocyte count
EFO:0010273	thoracic aortic calcification measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D015140	Dementia, Vascular	C10.228.140.300.400; C10.228.140.300.510.800.500; C10.228.140.380.230; C10.228.140.695.500; C14.907.137.126.372.500; C14.907.253.560.350.500; F03.615.400.350

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
Benzo(a)pyrene	decreases expression, increases expression	4
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
arsenite	decreases reaction, affects binding	1
sodium arsenite	decreases expression	1
manganese chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	decreases expression	1
Cadmium	increases abundance, increases expression	1
Calcitriol	decreases expression, affects cotreatment	1

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B5G5	LCPHi002-A	Induced pluripotent stem cell	Female
CVCL_E0SZ	Ubigene HeLa VPS13A KO	Cancer cell line	Female
CVCL_E9XV	K-562 VPS13A/VPS13C DKO clone 1	Cancer cell line	Female
CVCL_E9XW	K-562 VPS13A/VPS13C DKO clone 2	Cancer cell line	Female
CVCL_TX49	HAP1 VPS13A (-) 1	Cancer cell line	Male
CVCL_XV02	HAP1 VPS13A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00165763	PHASE4	COMPLETED	Efficacy and Safety of Donepezil Hydrochloride (Aricept) in Vascular Dementia
NCT00847860	PHASE4	COMPLETED	Cilostazol Verse Asprin for Vascular Dementia in Poststroke Patients With White Matter Lesions
NCT00947531	PHASE4	COMPLETED	A Clinical Trial to Evaluate the Safety and Efficacy of 20 ml Cerebrolysin in Patients With Vascular Dementia
NCT00950430	PHASE4	ENROLLING_BY_INVITATION	Imaging of Brain Amyloid Plaques in the Aging Population
NCT00099216	PHASE3	COMPLETED	Efficacy and Safety of Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00130338	PHASE3	COMPLETED	Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00209456	PHASE3	COMPLETED	Dopamine Transporter Scintigraphy Imaging (DAT-Imaging) in Patients With Lewy Body Dementia
NCT00249158	PHASE3	COMPLETED	A Study of the Effectiveness and Safety of Risperidone in the Treatment of Behavioral Disturbances in Patients With Dementia
NCT00261573	PHASE3	COMPLETED	A Study of the Safety and Effectiveness of Galantamine Versus Placebo in the Treatment of Patients With Vascular Dementia or Mixed Dementia
NCT00621647	PHASE3	COMPLETED	Seroquel- Agitation Associated With Dementia
NCT02453932	PHASE3	COMPLETED	Efficacy and Safety of Tianzhi Granule in Mild to Moderate Vascular Dementia
NCT03682185	PHASE3	COMPLETED	The Healthy Patterns Sleep Study
NCT03789760	PHASE3	COMPLETED	The Clinical Trial of Chinese Herbal Medicine (SaiLuoTong) Capsule
NCT03804229	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Butylphthalide Soft Capsule for the Treatment of Vascular Dementia
NCT03986424	PHASE3	COMPLETED	Local Study of Akatinol Memantine in VaD in Russia
NCT04552041	PHASE3	COMPLETED	Prospekta in the Treatment of Cognitive, Behavioral and Psychiatric Disorders in Patients With Vascular Dementia.
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT01466543	PHASE2	UNKNOWN	Effect of Zydena (Udenafil) on Cerebral Blood Flow and Peripheral Blood Viscosity
NCT01475578	PHASE2	COMPLETED	Study of STA-1 Capsule in Patients With Vascular Dementia (Marrow-Sea Deficiency)
NCT01608217	PHASE2	COMPLETED	Delta-THC in Dementia
NCT01761227	PHASE2	COMPLETED	Efficacy and Safety of Fufangdanshen Tablets in Mild to Moderate Vascular Dementia
NCT01953705	PHASE2	UNKNOWN	n-3 PUFA for Vascular Cognitive Aging
NCT01965756	PHASE2	COMPLETED	Effect of Insulin Sensitizer Metformin on AD Biomarkers
NCT01978730	PHASE2	UNKNOWN	The Clinical Trial of Chinese Herbal Medicine SaiLuoTong Capsule
NCT02467413	PHASE2	WITHDRAWN	BAC in Patient With Alzheimer’s Disease or Vascular Dementia
NCT03230071	PHASE2	COMPLETED	Efficacy and Safety of TMBCZG in Mild to Moderate Vascular Dementia
NCT04109963	PHASE2	UNKNOWN	Trial of Remote Ischemic Pre-conditioning in Vascular Cognitive Impairment
NCT05371639	PHASE2	UNKNOWN	Efficacy and Safety of Tian Ma Bian Chun Zhi Gan Tablets in Mild to Moderate Vascular Dementia
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00457769	PHASE1	UNKNOWN	Aricept to Improve Functional Tasks in Vascular Dementia
NCT03702543	PHASE1	UNKNOWN	Managing Vascular Dementia Risk Factors With SymTrend
NCT04567745	PHASE1	COMPLETED	Automated Retinal Image Analysis System (EyeQuant) for Computation of Vascular Biomarkers
NCT02098824	PHASE2/PHASE3	UNKNOWN	Symptomatic Treatment of Vascular Cognitive Impairment
NCT04248270	PHASE1/PHASE2	UNKNOWN	A Noval Tau Tracer in Young Onset Dementia
NCT00172900	Not specified	UNKNOWN	MRS and DTI of White Matter in Alzheimer’s Disease
NCT00506818	Not specified	COMPLETED	Cognitive and Emotional Impairment After Stroke
NCT00889603	Not specified	COMPLETED	Non-Interventional Study With Aricept® Evess
NCT01208675	Not specified	COMPLETED	The Swedish BioFINDER Study
NCT01345110	Not specified	COMPLETED	A Longitudinal Multidimensional Population Study on Brain Aging