VPS13D

vacuolar protein sorting 13 homolog D, the group of bridge-like lipid transfer protein family|Small nucleolar RNA protein coding host genes

Basic information

Region (hg38): 1:12230030-12512047

Links

ENSG00000048707 ∙ NCBI:55187 ∙ OMIM:608877 ∙ HGNC:23595 ∙ Uniprot:Q5THJ4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive cerebellar ataxia-saccadic intrusion syndrome (Strong), mode of inheritance: AR
• autosomal recessive cerebellar ataxia-saccadic intrusion syndrome (Supportive), mode of inheritance: AR
• autosomal recessive cerebellar ataxia-saccadic intrusion syndrome (Moderate), mode of inheritance: AR
• autosomal recessive cerebellar ataxia-saccadic intrusion syndrome (Strong), mode of inheritance: AR
• Leigh syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia, autosomal recessive 4	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	Neurologic	29518281; 29604224

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS13D gene.

• not provided (22 variants)
• Autosomal recessive cerebellar ataxia-saccadic intrusion syndrome (6 variants)
• Autosomal recessive cerebellar ataxia (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS13D 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	286	32	323
missense		6	551	20	16	593
nonsense	13	7				20
start loss						0
frameshift	12	3				15
inframe indel			3			3
splice donor/acceptor (+/-2bp)	2	3				5
splice region	1	1	15	41	5	63
non coding		1	3	131	37	172
Total	27	20	562	437	85

Highest pathogenic variant AF is 0.0000197

Variants in VPS13D

This is a list of pathogenic ClinVar variants found in the VPS13D region.

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

Position	Type	Phenotype	Significance	ClinVar
1-12234276-G-A		VPS13D-related disorder	Uncertain significance (Mar 30, 2023)
1-12234280-T-C		Inborn genetic diseases	Uncertain significance (Apr 12, 2024)
1-12234283-T-C			Uncertain significance (Feb 14, 2023)
1-12234302-C-T			Likely benign (Jan 05, 2024)
1-12234322-A-G		Inborn genetic diseases	Uncertain significance (Jul 26, 2022)
1-12234354-C-A			Uncertain significance (Nov 22, 2023)
1-12234357-C-T		Inborn genetic diseases	Uncertain significance (Oct 02, 2023)
1-12234363-G-C		Inborn genetic diseases	Uncertain significance (May 22, 2024)
1-12242330-G-A			Benign (May 16, 2021)
1-12242499-G-C			Likely benign (Aug 30, 2022)
1-12242520-T-C			Likely benign (Dec 11, 2023)
1-12242538-A-G			Benign (Nov 16, 2023)
1-12242549-A-G			Uncertain significance (May 19, 2021)
1-12242583-C-G		VPS13D-related disorder	Likely benign (Dec 21, 2023)
1-12242585-A-T			Uncertain significance (May 23, 2022)
1-12242601-C-A			Likely benign (Jun 20, 2023)
1-12242603-A-G			Likely benign (Aug 23, 2023)
1-12244229-T-G			Likely benign (Aug 13, 2022)
1-12244234-T-C			Likely benign (Sep 01, 2022)
1-12244235-TCTC-T			Likely benign (Dec 21, 2022)
1-12244253-T-C		VPS13D-related disorder	Likely benign (Dec 16, 2019)
1-12244266-C-T		See cases	Uncertain significance (Mar 23, 2023)
1-12244298-C-CCCTT			Pathogenic (Apr 30, 2018)
1-12244312-C-T			Uncertain significance (Oct 03, 2023)
1-12244321-G-C			Uncertain significance (Oct 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS13D	protein_coding	protein_coding	ENST00000358136	69	281976

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000107	1.00	125641	0	107	125748	0.000426

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.50	2029	2.37e+3	0.856	0.000134	28782
Missense in Polyphen		683	923.31	0.73973		11470
Synonymous	0.0923	905	909	0.996	0.0000516	8653
Loss of Function	9.80	55	207	0.265	0.0000120	2445

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00129	0.00129
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000598	0.000598
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000417	0.000404
Middle Eastern	0.000598	0.000598
South Asian	0.000327	0.000327
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions in promoting mitochondrial clearance by mitochondrial autophagy (mitophagy), also possibly by positively regulating mitochondrial fission (PubMed:29307555). Mitophagy plays an important role in regulating cell health and mitochondrial size and homeostasis (PubMed:29307555). {ECO:0000269|PubMed:29307555}.
• Disease: DISEASE: Note=Variants in VPS13D may be the cause of childhood onset movement disorders, characterized in most cases by developmental delay, axial hypotonia and hyperkinetic movement disorders associated with spastic paraparesis, as well as truncal and appendicular ataxia. {ECO:0000269|PubMed:29518281}.

Recessive Scores

• pRec: 0.114

Intolerance Scores

• loftool: 0.655
• rvis_EVS: -4.23
• rvis_percentile_EVS: 0.14

Haploinsufficiency Scores

• pHI: 0.276
• hipred: Y
• hipred_score: 0.563
• ghis: 0.587

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.582

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vps13d
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: protein targeting to vacuole;mitochondrion organization;protein retention in Golgi apparatus;positive regulation of mitophagy
• Cellular component: cell;extrinsic component of membrane;extracellular exosome