COPB2

Chr 3ARAD

coat protein complex I subunit beta 2

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

COPB2 encodes a subunit of the coatomer complex that mediates vesicular trafficking between the endoplasmic reticulum and Golgi apparatus and is essential for retrograde transport of proteins back to the ER. Mutations cause autosomal recessive primary microcephaly and childhood-onset osteoporosis with developmental delay, indicating critical roles in brain development and bone metabolism. The gene is highly constrained against loss-of-function variation (pLI 1.0, LOEUF 0.089), reflecting its essential cellular function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/ADLOEUF 0.092 OMIM phenotypes
Clinical SummaryCOPB2
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.09LOEUF
pLI 1.000
Z-score 6.64
OE 0.02 (0.010.09)
Highly constrained

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

Missense Constraint
2.56Z-score
OE missense 0.67 (0.610.73)
318 obs / 475.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.02 (0.010.09)
00.351.4
Missense OE0.67 (0.610.73)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 1 / 53.3Missense obs/exp: 318 / 475.2Syn Z: 0.95
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCOPB2-related developmental delay and osteopeniaLOFAD
limitedCOPB2-related developmental delay and microcephalyOTHERAR
DN
0.3694th %ile
GOF
0.2994th %ile
LOF
0.71top 10%

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

LOFprediction above median · 1 literature citation · LOEUF 0.09

Literature Evidence

LOFCOPB2 loss of function causes a coatopathy with osteoporosis and developmental delay.PMID:34450031

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

0 submitted variants 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.

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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