VPS33B

Chr 15AR

VPS33B late endosome and lysosome associated

Also known as: KDIDAR, PFIC12

Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene is a member of the Sec-1 domain family, and encodes the human ortholog of rat Vps33b which is homologous to the yeast class C Vps33 protein. The mammalian class C vacuolar protein sorting proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway. Mutations in this gene are associated with arthrogryposis-renal dysfunction-cholestasis syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

OMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.963 OMIM phenotypes
Clinical SummaryVPS33B
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Gene-Disease Validity (ClinGen)
arthrogryposis, renal dysfunction, and cholestasis 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.96LOEUF
pLI 0.000
Z-score 1.76
OE 0.71 (0.530.96)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.36Z-score
OE missense 0.94 (0.861.04)
314 obs / 332.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.71 (0.530.96)
00.351.4
Missense OE?0.94 (0.861.04)
00.61.4
Synonymous OE?0.96
01.21.6
LoF obs/exp: 31 / 43.5Missense obs/exp: 314 / 332.7Syn Z: 0.32

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

VPS33B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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