VPS33B

Chr 15AR

VPS33B late endosome and lysosome associated

Also known as: KDIDAR, PFIC12

VPS33B encodes a protein that mediates vesicle trafficking to lysosomes and is required for proper collagen processing and maintenance of cellular polarity in epithelial cells. Mutations cause autosomal recessive disorders including arthrogryposis-renal dysfunction-cholestasis syndrome, progressive familial intrahepatic cholestasis type 12, and keratoderma-ichthyosis-deafness syndrome, affecting multiple organ systems including liver, kidney, skin, and musculoskeletal system. The gene shows extreme intolerance to loss-of-function variants (pLI near 1), indicating that complete protein loss is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
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 OE0.71 (0.530.96)
00.351.4
Missense OE0.94 (0.861.04)
00.61.4
Synonymous OE0.96
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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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