VPS13A

Chr 9AR

vacuolar protein sorting 13 homolog A

NCBI Gene: 23230ENSG00000197969UniProt: Q96RL7

Mediates the transfer of lipids between membranes at organelle contact sites (By similarity). Binds phospholipids (PubMed:34830155). Required for the formation or stabilization of ER-mitochondria contact sites which enable transfer of lipids between the ER and mitochondria (PubMed:30741634). Negatively regulates lipid droplet size and motility (PubMed:30741634). Required for efficient lysosomal protein degradation (PubMed:30709847)

Primary Disease Associations & Inheritance

ChoreoacanthocytosisMIM #200150
AR
549
ClinVar variants
75
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— VPS13A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
75 Pathogenic / Likely Pathogenic· 330 VUS of 549 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.48LOEUF
pLI 0.000
Z-score 7.34
OE 0.40 (0.32–0.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.76Z-score
OE missense 0.88 (0.84–0.92)
1408 obs / 1606.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.40 (0.32–0.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.84–0.92)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 68 / 171.9Missense obs/exp: 1408 / 1606.3Syn Z: 0.13

ClinVar Variant Classifications

549 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic50
VUS330
Likely Benign137
Benign3
Conflicting4
25
Pathogenic
50
Likely Pathogenic
330
VUS
137
Likely Benign
3
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
0
13
0
25
Likely Pathogenic
36
1
13
0
50
VUS
3
285
31
11
330
Likely Benign
0
12
82
43
137
Benign
0
0
3
0
3
Conflicting
—4
Total5129814254549

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

VPS13A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Choreoacanthocytosis

MIM #200150

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — VPS13A
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Premature skeletal muscle aging in VPS13A deficiency relates to impaired autophagy.
Riccardi V et al.·Acta Neuropathol Commun
2025
Compound Heterozygous VPS13A Variants in a Patient with Neuroacanthocytosis: A Case Report and Review of the Literature.
Kim A et al.·Lab Med
2022Review
A chorea-acanthocytosis patient with novel mutations in the VPS13A gene without acanthocyte.
Jin S et al.·Neurol Sci
2024Review
The association of lipid transfer protein VPS13A with endosomes is mediated by sorting nexin SNX5.
Tornero-Écija A et al.·Life Sci Alliance
2023
An Autopsy Series of Seven Cases of VPS13A Disease (Chorea-Acanthocytosis).
Ditzel RM Jr et al.·Mov Disord
2023Case report
Novel heterozygous VPS13A pathogenic variants in chorea-neuroacanthocytosis: a case report.
Chen X et al.·BMC Neurol
2023Case report
Exome sequencing of choreoacanthocytosis reveals novel mutations in VPS13A and co-mutation in modifier gene(s).
Chaudhari S et al.·Mol Genet Genomics
2023
The Diverse Neuromuscular Spectrum of VPS13A Disease.
Buchberger A et al.·Ann Clin Transl Neurol
2026
Clinical Features and Novel Pathogenic Variants of Chinese Patients With McLeod Syndrome and Chorea-Acanthocytosis.
Yu H et al.·Mol Genet Genomic Med
2024Cohort
A partnership between the lipid scramblase XK and the lipid transfer protein VPS13A at the plasma membrane.
Guillén-Samander A et al.·Proc Natl Acad Sci U S A
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools