COPB2

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

Basic information

Region (hg38): 3:139353946-139389736

Links

ENSG00000184432 ∙ NCBI:9276 ∙ OMIM:606990 ∙ HGNC:2232 ∙ Uniprot:P35606 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive primary microcephaly (Supportive), mode of inheritance: AR
• osteoporosis, childhood- or juvenile-onset, with developmental delay (Moderate), mode of inheritance: AD
• microcephaly 19, primary, autosomal recessive (Limited), mode of inheritance: AR
• microcephaly 19, primary, autosomal recessive (Limited), mode of inheritance: Unknown
• osteoporosis, childhood- or juvenile-onset, with developmental delay (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteoporosis, childhood- or juvenile-onset, with developmental delay; Microcephaly 19, primary, autosomal recessive	AD/AR	General	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	Musculoskeletal; Neurologic	29036432; 34450031

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COPB2 gene.

• not provided (1 variants)
• Osteoporosis, childhood- or juvenile-onset, with developmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COPB2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				13	2	15
missense			33	3	4	40
nonsense			1			1
start loss						0
frameshift	1	1	3			5
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			6	2	1	9
non coding		1	9	23	16	49
Total	1	2	46	39	22

Variants in COPB2

This is a list of pathogenic ClinVar variants found in the COPB2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-139355352-T-A			Benign (Jun 19, 2018)
3-139355444-T-C			Benign (Jul 27, 2018)
3-139355667-C-A			Likely benign (Nov 27, 2023)
3-139355667-C-T			Likely benign (May 30, 2022)
3-139355676-T-G			Likely benign (Aug 30, 2023)
3-139355679-C-T		MRPS22-related disorder	Likely benign (Dec 17, 2019)
3-139355686-G-A		Inborn genetic diseases	Uncertain significance (Oct 26, 2022)
3-139355699-A-C		Inborn genetic diseases	Uncertain significance (Aug 04, 2021)
3-139355709-G-T		Inborn genetic diseases	Uncertain significance (Nov 07, 2022)
3-139355715-TCACGTG-T			Uncertain significance (Dec 19, 2021)
3-139355719-G-A		Inborn genetic diseases	Likely benign (Aug 28, 2024)
3-139355739-G-C			Uncertain significance (Jul 30, 2022)
3-139355741-C-A			Likely pathogenic (Apr 15, 2019)
3-139355741-C-T		Hypotonia with lactic acidemia and hyperammonemia • MRPS22-related disorder	Conflicting classifications of pathogenicity (Dec 12, 2024)
3-139355746-C-T		Hypotonia with lactic acidemia and hyperammonemia	Uncertain significance (-)
3-139355756-AG-A		Inborn genetic diseases	Uncertain significance (Feb 01, 2022)
3-139355766-T-C			Likely benign (Mar 04, 2021)
3-139355772-G-T			Uncertain significance (Aug 16, 2022)
3-139355793-A-G			Uncertain significance (Dec 02, 2021)
3-139355796-GT-G		Combined oxidative phosphorylation deficiency • not specified	Conflicting classifications of pathogenicity (Feb 14, 2023)
3-139355796-G-GT		not specified • MRPS22-related disorder	Benign/Likely benign (Aug 21, 2023)
3-139355799-T-C			Likely benign (Sep 01, 2022)
3-139355957-T-C			Benign (Nov 27, 2018)
3-139355961-AAC-A			Likely benign (Jul 27, 2020)
3-139355995-T-G			Benign (Jun 26, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COPB2	protein_coding	protein_coding	ENST00000333188	22	34133

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.01e-8	125704	0	15	125719	0.0000597

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.56	318	475	0.669	0.0000234	5971
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000276	0.000275
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000325	0.000323
European (Non-Finnish)	0.0000265	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Glycosphingolipid biosynthesis - neolactoseries;Post-translational protein modification;Metabolism of proteins;Tyrosine metabolism;Proteoglycan biosynthesis;Androgen and estrogen biosynthesis and metabolism;Glycosphingolipid biosynthesis - ganglioseries;Glycosphingolipid biosynthesis - globoseries;Purine metabolism;Pyrimidine metabolism;Glycosphingolipid metabolism;Phosphatidylinositol phosphate metabolism;Prostaglandin formation from arachidonate;Methionine and cysteine metabolism;Aminosugars metabolism;Galactose metabolism;O-Glycan biosynthesis;C21-steroid hormone biosynthesis and metabolism;Glycerophospholipid metabolism;Vitamin B9 (folate) metabolism;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;COPI-dependent Golgi-to-ER retrograde traffic;Golgi-to-ER retrograde transport;COPI-mediated anterograde transport;TNFalpha;N-Glycan biosynthesis;ER to Golgi Anterograde Transport;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.196

Intolerance Scores

• loftool: 0.0915
• rvis_EVS: -0.93
• rvis_percentile_EVS: 9.47

Haploinsufficiency Scores

• pHI: 0.516
• hipred: Y
• hipred_score: 0.765
• ghis: 0.640

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.855

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Copb2
• Phenotype: growth/size/body region phenotype; cellular phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: copb2
• Affected structure: muscle cell
• Phenotype tag: abnormal
• Phenotype quality: structure

Gene ontology

• 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
• Cellular component: Golgi membrane;endoplasmic reticulum membrane;cytosol;COPI vesicle coat;transport vesicle
• Molecular function: structural molecule activity;protein binding