VPS26B

Chr 11

VPS26 retromer complex component B

Also known as: Pep8b

NCBI Gene: 112936ENSG00000151502UniProt: Q4G0F5

VPS26B encodes a component of the retromer cargo-selective complex that prevents missorting of transmembrane cargo proteins into the lysosomal degradation pathway and mediates retrograde transport from endosomes to the trans-Golgi network and plasma membrane recycling. This highly constrained gene (pLI=0.97, LOEUF=0.32) has not yet been definitively associated with human disease, though its critical role in endosomal trafficking suggests mutations would likely cause developmental abnormalities. The inheritance pattern for VPS26B-related disorders has not been established.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
91
P/LP submissions
0%
P/LP missense
0.32
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— VPS26B
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
90 unique Pathogenic / Likely Pathogenic· 36 VUS of 141 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.32LOEUF
pLI 0.966
Z-score 3.34
OE 0.07 (0.02–0.32)
Highly constrained

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

Missense Constraint
2.02Z-score
OE missense 0.62 (0.53–0.71)
134 obs / 217.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.07 (0.02–0.32)
0≤0.351.4
Missense OE0.62 (0.53–0.71)
0≤0.61.4
Synonymous OE1.19
0≤1.21.6
LoF obs/exp: 1 / 15.0Missense obs/exp: 134 / 217.9Syn Z: -1.40
DN
0.4190th %ile
GOF
0.3491th %ile
LOF
0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.32

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

141 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic83
Likely Pathogenic7
VUS36
Likely Benign1
83
Pathogenic
7
Likely Pathogenic
36
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
83
0
83
Likely Pathogenic
0
0
7
0
7
VUS
0
23
13
0
36
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total0231040127

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

View in ClinVar →

Protein Context — Lollipop Plot

VPS26B · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients