COPB2

Chr 3ARAD

coat protein complex I subunit beta 2

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

NCBI Gene: 9276 ENSG00000184432 UniProt: P35606 OMIM: 606990

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismAR/ADLOEUF 0.092 OMIM phenotypes

Clinical Summary— COPB2

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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.

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ClinVar Variants

11 unique Pathogenic / Likely Pathogenic· 117 VUS of 239 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?

0.09LOEUF

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?

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?

LoF OE?0.02 (0.01–0.09)

0≤0.351.4

Missense OE?0.67 (0.61–0.73)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

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

This gene — mechanism propensity

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 · 73% of P/LP variants are LoF · LOEUF 0.09

Literature Evidence

LOFCOPB2 loss of function causes a coatopathy with osteoporosis and developmental delay.1

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

References

1.PMID 34450031 ↗

ClinVar Variant Classifications

239 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic5

VUS117

Likely Benign61

Benign14

Conflicting6

Pathogenic

Likely Pathogenic

117

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	1	2	0	6
Likely Pathogenic	5	0	0	0	5
VUS	5	103	7	2	117
Likely Benign	0	7	23	31	61
Benign	0	4	8	2	14
Conflicting	—				6
Total	13	115	40	35	209

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap COPB2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →