VPS13A

protein-coding

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

Gene summary

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. [provided by RefSeq, Jul 2008]

Previous symbols:

CHAC

MANE transcript

NM_033305.3

Inheritance

ClinVar variants

P:518U:847B:1215

Top phenotype

Choreoacanthocytosis

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr9:77,177,445-77,421,537

External References & Databases

Ensembl (ENSG00000197969)

Transcript & Mutation Effects

hg38 • Region Span ~244.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

VPS13A-related neurodegenerative diseaseSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008695

Submitter: Genomics England PanelApp

VPS13A-related neurodegenerative diseaseSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008695

Submitter: Labcorp Genetics (formerly Invitae)

VPS13A-related neurodegenerative diseaseSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008695

Submitter: Orphanet

VPS13A-related neurodegenerative diseaseDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008695

Submitter: Natera

VPS13A-related neurodegenerative diseaseDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008695

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

ChoreoacanthocytosisAR

Manifestation: Hematologic; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 4255726; 5677189; 4647152; 666266; 7081216; 7073550; 4026606; 1998879; 7936287; 8599563; 9382101; 10371080; 11381253; 11381254; 12404112; 15918062; 15824261; 17998451; 18584183; 18661137; 20301561; 21598378; 22038564; 23199253

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VPS13A variants in ClinVar

9 Conditions Cataloged

not providedTotal: 2988

VPS13A-related neurodegenerative diseaseTotal: 764

Inborn genetic diseasesTotal: 401

not specifiedTotal: 76

VPS13A-related disorderTotal: 44

Abnormality of the nervous systemTotal: 1

Vascular dementiaTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033305.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar	2 clinvar	38 clinvar	1125 clinvar	13 clinvar	1179
missense	2 clinvar	11 clinvar	797 clinvar	70 clinvar	6 clinvar	886
nonsense	70 clinvar	54 clinvar	3 clinvar			127
start loss		2 clinvar				2
frameshift	152 clinvar	94 clinvar	2 clinvar			248
splice donor/acceptor (+/-2bp)	12 clinvar	118 clinvar	7 clinvar		1 clinvar	138
Total	237	281	847	1195	20	2580

Highest pathogenic variant AF is 0.0016904583

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033305.3	RefSeq	NP_150648.2	72	MANE Select
ENST00000360280.8	Ensembl	ENSP00000353422.3	72	MANE Select
NM_001018037.2	RefSeq	NP_001018047.1	71	Standard
NM_001018038.3	RefSeq	NP_001018048.1	69	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein targeting to vacuole
Golgi to endosome transport
autophagy
nervous system development
locomotory behavior

Molecular Function

protein binding

Cellular Component

cytosol
extrinsic component of membrane
dense core granule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000360280
Coding exons: 72
Length: 244189
Individuals with no LoFs: 125549
Homozygous LoFs: 0
Heterozygous LoFs: 199
Defined: 125748
p: 0.000792

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.76	1408	1.61e+3	0.877	0.0000790	20931
Missense (PolyPhen)		381	522.91	0.72862		6900
Synonymous	0.127	540	544	0.993	0.0000275	5821
Loss of Function	7.34	68	172	0.396	0.00000884	2219

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00076	0.00074	rare
Latino/Admixed American	0.00084	0.00084	rare
Ashkenazi Jewish	0.00070	0.00069	rare
East Asian	0.0011	0.0011	notable
Finnish	0.00056	0.00055	rare
European (Non-Finnish)	0.00081	0.00080	rare
South Asian	0.00069	0.00069	rare
Other	0.00098	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in the control of protein cycling through the trans-Golgi network to early and late endosomes, lysosomes and plasma membrane.;

Recessive Scores

pRec: 0.232

Intolerance Scores

LoFtool: 0.900
RVIS EVS: -1.85
RVIS percentile EVS: 2.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.436

Gene Damage Prediction

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