VIPAS39

Chr 14AR

VPS33B interacting protein, apical-basolateral polarity regulator, spe-39 homolog

Also known as: C14orf133, SPE-39, SPE39, VIPAR, VPS16B, hSPE-39

NCBI Gene: 63894 ENSG00000151445 UniProt: Q9H9C1 OMIM: 613401

The VIPAS39 protein functions in endosome to lysosome transport and vesicle tethering, playing a critical role in intracellular trafficking and maintaining cellular polarity in epithelial cells. Mutations cause arthrogryposis, renal dysfunction, and cholestasis 2, a multisystem disorder affecting joints, kidneys, and liver function. This condition follows autosomal recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Involved in endosome to lysosome transport and intracellular protein transport. Acts upstream of or within collagen metabolic process and peptidyl-lysine hydroxylation. Located in Golgi apparatus and endosome. Part of vesicle tethering complex. Implicated in arthrogryposis, renal dysfunction, and cholestasis 2. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.801 OMIM phenotype

Clinical Summary— VIPAS39

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Gene-Disease Validity (ClinGen)

arthrogryposis, renal dysfunction, and cholestasis 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

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

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ClinVar Variants

32 unique Pathogenic / Likely Pathogenic· 137 VUS of 385 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.000

Z-score 2.54

OE 0.55 (0.39–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.86Z-score

OE missense 0.85 (0.77–0.95)

229 obs / 268.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.55 (0.39–0.80)

0≤0.351.4

Missense OE?0.85 (0.77–0.95)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 21 / 37.9Missense obs/exp: 229 / 268.6Syn Z: 0.86

ClinVar Variant Classifications

385 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic11

VUS137

Likely Benign123

Benign50

Conflicting29

Pathogenic

Likely Pathogenic

137

VUS

123

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	19	1	1	0	21
Likely Pathogenic	9	2	0	0	11
VUS	3	121	9	4	137
Likely Benign	1	4	77	41	123
Benign	0	0	47	3	50
Conflicting	—				29
Total	32	128	134	48	371

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap VIPAS39 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →