VPS13D

Chr 1AR

vacuolar protein sorting 13 homolog D

Also known as: BLTP5D, SCA24, SCAR4, SCASI

NCBI Gene: 55187 ENSG00000048707 UniProt: Q5THJ4 OMIM: 608877

The protein belongs to the vacuolar-protein-sorting-13 family and functions in trafficking membrane proteins between the trans-Golgi network and prevacuolar compartment. Biallelic mutations cause spinocerebellar ataxia, autosomal recessive 4, following an autosomal recessive inheritance pattern. The gene is highly intolerant to loss-of-function variants, suggesting pathogenicity occurs through disrupted intracellular membrane protein trafficking.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM

This gene encodes a protein belonging to the vacuolar-protein-sorting-13 gene family. In yeast, vacuolar-protein-sorting-13 proteins are involved in trafficking of membrane proteins between the trans-Golgi network and the prevacuolar compartment. While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode distinct isoforms. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

ARLOEUF 0.331 OMIM phenotype

Clinical Summary— VPS13D

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Gene-Disease Validity (ClinGen)

Leigh syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.

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ClinVar Variants

77 unique Pathogenic / Likely Pathogenic· 943 VUS of 1836 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — VPS13D

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.33LOEUF

pLI 0.000

Z-score 9.80

OE 0.27 (0.21–0.33)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.50Z-score

OE missense 0.86 (0.82–0.89)

2029 obs / 2371.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.27 (0.21–0.33)

0≤0.351.4

Missense OE?0.86 (0.82–0.89)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 55 / 207.3Missense obs/exp: 2029 / 2371.0Syn Z: 0.09

ClinVar Variant Classifications

1836 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39

Likely Pathogenic38

VUS943

Likely Benign618

Benign95

Conflicting34

Pathogenic

Likely Pathogenic

943

VUS

618

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	38	1	0	0	39
Likely Pathogenic	26	9	3	0	38
VUS	2	915	21	5	943
Likely Benign	0	27	206	385	618
Benign	0	15	45	35	95
Conflicting	—				34
Total	66	967	275	425	1,767

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

View in ClinVar →

38 pathogenic / likely-pathogenic (of 56) ClinVar copy-number / structural variants overlap VPS13D — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →