VPS13A

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

Basic information

Region (hg38): 9:77177445-77421537

Previous symbols: [ "CHAC" ]

Links

ENSG00000197969 ∙ NCBI:23230 ∙ OMIM:605978 ∙ HGNC:1908 ∙ Uniprot:Q96RL7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• chorea-acanthocytosis (Strong), mode of inheritance: AR
• chorea-acanthocytosis (Strong), mode of inheritance: AR
• chorea-acanthocytosis (Supportive), mode of inheritance: AR
• chorea-acanthocytosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Choreoacanthocytosis	AR	General	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	Hematologic; Musculoskeletal; Neurologic	4255726; 5677189; 4647152; 666266; 7081216; 7073550; 4026606; 1998879; 7936287; 8599563; 9382101; 10371080; 11381253; 11381254; 12404112; 15918062; 15824261; 17998451; 18584183; 18661137; 20301561; 21598378; 22038564; 23199253

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS13A gene.

• not provided (239 variants)
• Chorea-acanthocytosis (27 variants)
• primray hypomagnesemia with secondary hypocalcemia (1 variants)
• VPS13A-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS13A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	1019	21	1045
missense		3	415	20	5	443
nonsense	78	6	1			85
start loss		1				1
frameshift	155	14	1			170
inframe indel			11			11
splice donor/acceptor (+/-2bp)	14	77	1		1	93
splice region	1		12	253	16	282
non coding	1		31	687	187	906
Total	248	101	465	1726	214

Highest pathogenic variant AF is 0.0000788

Variants in VPS13A

This is a list of pathogenic ClinVar variants found in the VPS13A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-77177473-G-C		Chorea-acanthocytosis	Uncertain significance (Jan 12, 2018)
9-77177522-G-A		Chorea-acanthocytosis	Uncertain significance (Jan 13, 2018)
9-77177522-G-C		Chorea-acanthocytosis	Benign (Jul 17, 2018)
9-77177524-G-A		Chorea-acanthocytosis	Benign (Aug 14, 2018)
9-77177547-G-C		Chorea-acanthocytosis	Uncertain significance (Jan 13, 2018)
9-77177555-C-T		Chorea-acanthocytosis	Uncertain significance (Jan 12, 2018)
9-77177557-C-T		Chorea-acanthocytosis	Uncertain significance (Jan 13, 2018)
9-77177689-A-T		Chorea-acanthocytosis	Uncertain significance (Apr 06, 2018)
9-77177705-A-T		Chorea-acanthocytosis	Likely pathogenic (Feb 07, 2022)
9-77177713-C-T			Likely benign (Dec 06, 2023)
9-77177716-G-A			Likely benign (Apr 09, 2023)
9-77177718-C-A		Chorea-acanthocytosis	Likely pathogenic (Mar 15, 2021)
9-77177725-C-G			Likely benign (Feb 03, 2023)
9-77177728-G-A			Likely benign (Jan 01, 2024)
9-77177740-C-T			Likely benign (Aug 30, 2022)
9-77177746-C-T			Likely benign (Nov 21, 2021)
9-77177748-T-TG			Pathogenic (Mar 16, 2021)
9-77177767-C-T			Likely benign (May 08, 2023)
9-77177768-T-C			Likely benign (Dec 03, 2023)
9-77177775-C-CG			Pathogenic (Feb 09, 2022)
9-77177776-G-A			Likely benign (Jun 29, 2023)
9-77177779-C-T			Likely benign (Oct 15, 2023)
9-77177781-A-AG			Pathogenic (May 05, 2020)
9-77177788-T-A			Likely benign (Apr 28, 2023)
9-77177788-T-C			Likely benign (Aug 20, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS13A	protein_coding	protein_coding	ENST00000360280	72	244189

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.31e-22	1.00	125549	0	199	125748	0.000792

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.76	1408	1.61e+3	0.877	0.0000790	20931
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00160	0.00158
Ashkenazi Jewish	0.000697	0.000695
East Asian	0.00114	0.00114
Finnish	0.000562	0.000554
European (Non-Finnish)	0.000810	0.000800
Middle Eastern	0.00114	0.00114
South Asian	0.000688	0.000686
Other	0.000985	0.000978

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.153
• hipred: N
• hipred_score: 0.414
• ghis: 0.536

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.436

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vps13a
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype

Gene ontology

• Biological process: protein targeting to vacuole;Golgi to endosome transport;autophagy;nervous system development;locomotory behavior;protein localization;social behavior;protein retention in Golgi apparatus
• Cellular component: cytosol;extrinsic component of membrane;dense core granule
• Molecular function: protein binding