VPS26B

protein-coding

VPS26 retromer complex component B

Gene summary

Predicted to be involved in intracellular protein transport and retrograde transport, endosome to Golgi. Predicted to act upstream of or within cellular response to type II interferon. Predicted to be located in early endosome and late endosome. Predicted to be part of retromer, cargo-selective complex. Predicted to be active in endosome. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_052875.5

Inheritance

—

ClinVar variants

U:27

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr11:134,224,671-134,247,788

External References & Databases

Transcript & Mutation Effects

hg38 • Region Span ~23.1 kb
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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VPS26B variants in ClinVar

1 Conditions Cataloged
not specifiedTotal: 23

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_052875.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
2
missense
24
clinvar
24
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
1
clinvar
1
Total00270027
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_052875.5RefSeqNP_443107.16MANE Select
ENST00000281187.10EnsemblENSP00000281187.56MANE Select
ENST00000525095.2EnsemblENSP00000434162.26Standard
ENST00000527586.1EnsemblENSP00000431672.12Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Endocytosis - Homo sapiens (human)

Biological Process

  • intracellular protein transport
  • regulation of macroautophagy
  • retrograde transport, endosome to Golgi
  • cellular response to interferon-gamma

Molecular Function

  • protein binding
  • protein transporter activity

Cellular Component

  • endosome
  • early endosome
  • late endosome
  • cytosol
  • retromer complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000281187
Coding exons
6
Length
23148
Individuals with no LoFs
125654
Homozygous LoFs
0
Heterozygous LoFs
3
Defined
125657
p
0.0000119
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.021342180.6150.00001352227
Missense (PolyPhen)4394.5970.45456952
Synonymous-1.4010487.41.190.00000539633
Loss of Function3.34114.90.06698.01e-7175

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000270.000026rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5. May be involved in retrograde transport of SORT1 but not of IGF2R. Acts redundantly with VSP26A in SNX-27 mediated endocytic recycling of SLC2A1/GLUT1 (By similarity). {ECO:0000250|UniProtKB:O75436, ECO:0000250|UniProtKB:Q8C0E2}.;

Recessive Scores

pRec
0.117

Intolerance Scores

LoFtool
0.0967
RVIS EVS
-0.52
RVIS percentile EVS
21.2

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.624

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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