COPB2

Chr 3ARAD

coat protein complex I subunit beta 2

Also known as: MCPH19, OPDD, beta'-COP

NCBI Gene: 9276ENSG00000184432UniProt: P35606

The Golgi coatomer complex (see MIM 601924) constitutes the coat of nonclathrin-coated vesicles and is essential for Golgi budding and vesicular trafficking. It consists of 7 protein subunits, including COPB2.[supplied by OMIM, Jul 2002]

Primary Disease Associations & Inheritance

?Microcephaly 19, primary, autosomal recessiveMIM #617800
AR
Osteoporosis, childhood- or juvenile-onset, with developmental delayMIM #619884
AD
231
ClinVar variants
33
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— COPB2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 117 VUS of 231 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.09LOEUF
pLI 1.000
Z-score 6.64
OE 0.02 (0.01–0.09)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.56Z-score
OE missense 0.67 (0.61–0.73)
318 obs / 475.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.02 (0.01–0.09)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.61–0.73)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 1 / 53.3Missense obs/exp: 318 / 475.2Syn Z: 0.95

ClinVar Variant Classifications

231 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic6
VUS117
Likely Benign60
Benign15
Conflicting6
27
Pathogenic
6
Likely Pathogenic
117
VUS
60
Likely Benign
15
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
23
0
27
Likely Pathogenic
4
0
2
0
6
VUS
3
98
14
2
117
Likely Benign
0
7
23
30
60
Benign
0
4
8
3
15
Conflicting
—6
Total101107035231

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

View in ClinVar →

Protein Context — Lollipop Plot

COPB2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

COPB2-related developmental delay and osteopenia

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

COPB2-related developmental delay and microcephaly

limited
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Microcephaly 19, primary, autosomal recessive

MIM #617800

Molecular basis of disorder known

Autosomal recessive

Osteoporosis, childhood- or juvenile-onset, with developmental delay

MIM #619884

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
High expression of COPB2 predicts adverse outcomes: A potential therapeutic target for glioma.
Zhou Y et al.·CNS Neurosci Ther
2020
COPB2 Is Upregulated in Prostate Cancer and Regulates PC-3 Cell Proliferation, Cell Cycle, and Apoptosis.
Mi Y et al.·Arch Med Res
2016
COPB2 loss of function causes a coatopathy with osteoporosis and developmental delay.
Marom R et al.·Am J Hum Genet
2021
Comprehensive pan-cancer single-cell analysis reveals glycolysis-related signatures as predictive biomarkers for immunotherapy response and their role in bladder cancer.
Li Y et al.·Int Immunopharmacol
2025
COPB2: A Novel Prognostic Biomarker That Affects Progression of HCC.
Zhang J et al.·Biomed Res Int
2021
Biochemical and localization analyses of putative type III secretion translocator proteins CopB and CopB2 of Chlamydia trachomatis reveal significant distinctions.
Chellas-Géry B et al.·Infect Immun
2011
COPB2 promotes cell proliferation and tumorigenesis through up-regulating YAP1 expression in lung adenocarcinoma cells.
Pu X et al.·Biomed Pharmacother
2018
Early prediction of COVID-19 severity using extracellular vesicle COPB2.
Fujita Y et al.·J Extracell Vesicles
2021
Copb2 is essential for embryogenesis and hypomorphic mutations cause human microcephaly.
DiStasio A et al.·Hum Mol Genet
2017Case report
Silencing of COPB2 inhibits the proliferation of gastric cancer cells and induces apoptosis via suppression of the RTK signaling pathway.
An C et al.·Int J Oncol
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
COPB2 drives gastric cancer progression via PI3K/AKT/NF-κB signaling: a multi-omics and functional study.
Li H et al.·Cell Adh Migr
2026🔓 Open AccessFunctional
Cell-penetrant peptides as novel inhibitors of the interaction of coatomer protein COPB2/RACK2 with protein kinase Cε and cargo proteins.
Olushola-Siedoks AA et al.·Biochim Biophys Acta Mol Cell Res
2026
COPB2 facilitates EDEM3-mediated mannose trimming to sustain ER homeostasis in ovarian cancer.
Li DX et al.·Cell Oncol (Dordr)
2025🔓 Open Access
COPB2 as a key regulator of cell growth in human osteosarcoma cells: Potential therapeutic target and prognostic indicator.
Cui Y et al.·J Bone Oncol
2025🔓 Open Access
COPB2 promotes hepatocellular carcinoma progression through regulation of YAP1 nuclear translocation.
Wu B et al.·Oncol Res
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools