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 (1157 variants)
Inborn_genetic_diseases (492 variants)
Autosomal_recessive_cerebellar_ataxia-saccadic_intrusion_syndrome (77 variants)
VPS13D-related_disorder (77 variants)
Fetal_akinesia_deformation_sequence_1 (2 variants)
Leigh_syndrome (2 variants)
Arthrogryposis_multiplex_congenita (2 variants)
Neurodevelopmental_disorder (1 variants)
Non-immune_hydrops_fetalis (1 variants)
Spinocerebellar_ataxia_type_4 (1 variants)
See_cases (1 variants)
Spinocerebellar_atrophy (1 variants)
not_specified (1 variants)
Autosomal_recessive_cerebellar_ataxia (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. These statistics are base on transcript: NM_000015378.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	338 clinvar	37 clinvar	379
missense		9 clinvar	818 clinvar	44 clinvar	16 clinvar	887
nonsense	20 clinvar	10 clinvar	1 clinvar			31
start loss						0
frameshift	15 clinvar	5 clinvar				20
splice donor/acceptor (+/-2bp)	2 clinvar	4 clinvar	1 clinvar			7
Total	37	28	824	382	53

Highest pathogenic variant AF is 0.0000272802

Loading clinvar variants...

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
Molecular function