COPB2

protein-coding

COPI coat complex subunit beta 2, the group of WD repeat domain containing|COPI coat complex

Gene summary

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]

MANE transcript

NM_004766.3

Inheritance

AR, AD

ClinVar variants

P:11U:136B:55

Top phenotype

Osteoporosis, childhood- or juvenile-onset, with developmental delay; Microcephaly 19, primary, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.02

Max pathogenic AF

—

Genomic locus

chr3:139,353,946-139,389,736

External References & Databases

Ensembl (ENSG00000184432)

Transcript & Mutation Effects

hg38 • Region Span ~35.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

microcephaly 19, primary, autosomal recessiveLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0054716

Submitter: Ambry Genetics

microcephaly 19, primary, autosomal recessiveLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0054716

Submitter: G2P

osteoporosis, childhood- or juvenile-onset, with developmental delayMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0859253

Submitter: Ambry Genetics

microcephaly 19, primary, autosomal recessiveLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0054716

Submitter: Labcorp Genetics (formerly Invitae)

autosomal recessive primary microcephalySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016660

Submitter: Orphanet

osteoporosis, childhood- or juvenile-onset, with developmental delaySTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859253

Submitter: Labcorp Genetics (formerly Invitae)

osteoporosis, childhood- or juvenile-onset, with developmental delaySTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859253

Submitter: G2P

Clinical Genomic Database (CGD)

Osteoporosis, childhood- or juvenile-onset, with developmental delay; Microcephaly 19, primary, autosomal recessiveAD/AR

Manifestation: Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 29036432; 34450031

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to COPB2 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 137

Inborn genetic diseasesTotal: 77

Osteoporosis, childhood- or juvenile-onset, with developmental delayTotal: 15

Microcephaly 19, primary, autosomal recessiveTotal: 7

COPB2-related disorderTotal: 7

not specifiedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004766.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	38 clinvar	1 clinvar	42
missense	1 clinvar		123 clinvar	12 clinvar	4 clinvar	140
nonsense		1 clinvar	3 clinvar			4
start loss						0
frameshift	2 clinvar	5 clinvar	3 clinvar			10
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	4 clinvar			6
Total	4	7	136	50	5	202

Highest pathogenic variant AF is 0.00000805609

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004766.3	RefSeq	NP_004757.1	22	MANE Select
ENST00000333188.10	Ensembl	ENSP00000329419.4	22	MANE Select
NM_001410834.1	RefSeq	NP_001397763.1	21	Standard
ENST00000503326.6	Ensembl	ENSP00000426682.2	22	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
copb2	Danio rerio	Structure: muscle cell Quality: structure abnormal

Gene / Model

Organism

Observed Phenotype

copb2

Danio rerio

Structure: muscle cell

Quality: structure

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vesicle-mediated transport
Membrane Trafficking
Glycosphingolipid biosynthesis - neolactoseries
Post-translational protein modification
Metabolism of proteins

Biological Process

intracellular protein transport
endoplasmic reticulum to Golgi vesicle-mediated transport
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
intra-Golgi vesicle-mediated transport
toxin transport

Molecular Function

structural molecule activity
protein binding

Cellular Component

Golgi membrane
endoplasmic reticulum membrane
cytosol
COPI vesicle coat
transport vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000333188
Coding exons: 22
Length: 34133
Individuals with no LoFs: 125704
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125719
p: 0.0000597

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.56	318	475	0.669	0.0000234	5971
Missense (PolyPhen)		101	209.15	0.4829		2590
Synonymous	0.950	150	166	0.906	0.00000819	1674
Loss of Function	6.64	1	53.3	0.0187	0.00000256	649

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00033	0.00032	rare
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non- clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity). {ECO:0000250}.;
Disease: DISEASE: Microcephaly 19, primary, autosomal recessive (MCPH19) [MIM:617800]: A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH19 affected individuals manifest severe developmental delay, failure to thrive, cortical blindness, and spasticity. Brain imaging show a simplified gyral pattern, thin corpus callosum, slight ventricular dilation, and delayed myelination. {ECO:0000269|PubMed:29036432}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.196

Intolerance Scores

LoFtool: 0.0915
RVIS EVS: -0.93
RVIS percentile EVS: 9.47

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.855

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium