COPB1

Summary

COPB1 (coat protein complex I subunit beta 1, HGNC:2231) is a protein-coding gene on chromosome 11p15.2, encoding Coatomer subunit beta (P53618). 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. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

This gene encodes a protein subunit of the coatomer complex associated with non-clathrin coated vesicles. The coatomer complex, also known as the coat protein complex 1, forms in the cytoplasm and is recruited to the Golgi by activated guanosine triphosphatases. Once at the Golgi membrane, the coatomer complex may assist in the movement of protein and lipid components back to the endoplasmic reticulum. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 1315 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Baralle-Macken syndrome (Limited, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 134 total — 2 pathogenic
• Phenotypes (HPO): 26
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_001144061

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2231
Approved symbol	COPB1
Name	coat protein complex I subunit beta 1
Location	11p15.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000129083
Ensembl biotype	protein_coding
OMIM	600959
Entrez	1315

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 21 protein_coding, 7 protein_coding_CDS_not_defined

ENST00000249923, ENST00000439561, ENST00000525214, ENST00000526191, ENST00000526527, ENST00000529210, ENST00000529866, ENST00000532088, ENST00000533096, ENST00000533533, ENST00000534234, ENST00000534771, ENST00000890278, ENST00000890281, ENST00000890283, ENST00000890285, ENST00000890287, ENST00000890289, ENST00000890291, ENST00000890293, ENST00000890295, ENST00000890296, ENST00000912857, ENST00000912858, ENST00000912859, ENST00000967459, ENST00000967460, ENST00000967461

RefSeq mRNA: 3 — MANE Select: NM_001144061 NM_001144061, NM_001144062, NM_016451

CCDS: CCDS7815

Canonical transcript exons

ENST00000439561 — 22 exons

Exon	Start	End
ENSE00000331854	14475785	14475945
ENSE00000331855	14474495	14474615
ENSE00000331859	14464911	14465030
ENSE00000703770	14461186	14461331
ENSE00000703791	14466282	14466426
ENSE00000703795	14468681	14468860
ENSE00000703797	14469336	14469563
ENSE00000703807	14476919	14477015
ENSE00000886037	14479569	14479714
ENSE00000886038	14480759	14480905
ENSE00000886039	14480990	14481097
ENSE00000886040	14483032	14483151
ENSE00000886041	14486367	14486504
ENSE00000886042	14488492	14488584
ENSE00000886043	14490565	14490679
ENSE00000886044	14493642	14493811
ENSE00001782713	14499707	14499811
ENSE00002170316	14457512	14457883
ENSE00003619041	14460208	14460297
ENSE00003649878	14498838	14498985
ENSE00003651964	14458532	14458687
ENSE00003672794	14494210	14494439

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 99.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 78.6429 / max 709.1135, expressed in 1825 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118747	46.4587	1819
118746	31.8309	1813
118745	0.3533	154

Top tissues by expression

302 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	99.69	gold quality
pancreatic ductal cell	CL:0002079	99.58	gold quality
corpus epididymis	UBERON:0004359	99.32	gold quality
caput epididymis	UBERON:0004358	99.29	gold quality
epithelial cell of pancreas	CL:0000083	99.26	gold quality
endothelial cell	CL:0000115	99.25	gold quality
germinal epithelium of ovary	UBERON:0001304	99.24	gold quality
epithelium of nasopharynx	UBERON:0001951	99.22	gold quality
tibia	UBERON:0000979	99.20	gold quality
nasopharynx	UBERON:0001728	99.20	gold quality
cauda epididymis	UBERON:0004360	99.12	gold quality
jejunal mucosa	UBERON:0000399	99.11	gold quality
parotid gland	UBERON:0001831	99.10	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.08	gold quality
bronchial epithelial cell	CL:0002328	99.07	gold quality
cartilage tissue	UBERON:0002418	99.05	gold quality
visceral pleura	UBERON:0002401	99.02	gold quality
mammary duct	UBERON:0001765	99.00	gold quality
epithelium of mammary gland	UBERON:0003244	98.98	gold quality
pylorus	UBERON:0001166	98.97	gold quality
hair follicle	UBERON:0002073	98.92	gold quality
skin of hip	UBERON:0001554	98.91	gold quality
pleura	UBERON:0000977	98.88	gold quality
colonic mucosa	UBERON:0000317	98.87	gold quality
seminal vesicle	UBERON:0000998	98.86	gold quality
epithelium of bronchus	UBERON:0002031	98.86	gold quality
bronchus	UBERON:0002185	98.86	gold quality
parietal pleura	UBERON:0002400	98.86	gold quality
pigmented layer of retina	UBERON:0001782	98.85	gold quality
nasal cavity epithelium	UBERON:0005384	98.84	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting COPB1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-150-3P	99.43	70.51	920
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-4751	98.80	64.95	525

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• Endogenous ANO1 was associated with COPB1 in U251 glioblastoma cells, and silencing of COPB1 enhanced surface expression and whole-cell currents of ANO1 in these cells. Taken together, these data suggest that COPB1 negatively regulates ANO1 surface expression. (PMID:27207835)
• An integrative pan-cancer analysis of COPB1 based on data mining. (PMID:32986658)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	copb1	ENSDARG00000056557
mus_musculus	Copb1	ENSMUSG00000030754
rattus_norvegicus	Copb1	ENSRNOG00000057623
drosophila_melanogaster	betaCOP	FBGN0008635
caenorhabditis_elegans		WBGENE00021292

Protein

Protein identifiers

Coatomer subunit beta — P53618 (reviewed: P53618)

Alternative names: Beta-coat protein

All UniProt accessions (4): P53618, E9PKQ1, E9PP63, E9PP73

UniProt curated annotations — full annotation on UniProt →

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. Plays a functional role in facilitating the transport of kappa-type opioid receptor mRNAs into axons and enhances translation of these proteins. Required for limiting lipid storage in lipid droplets. Involved in lipid homeostasis by regulating the presence of perilipin family members PLIN2 and PLIN3 at the lipid droplet surface and promoting the association of adipocyte surface triglyceride lipase (PNPLA2) with the lipid droplet to mediate lipolysis. Involved in the Golgi disassembly and reassembly processes during cell cycle. Involved in autophagy by playing a role in early endosome function. Plays a role in organellar compartmentalization of secretory compartments including endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC), Golgi, trans-Golgi network (TGN) and recycling endosomes, and in biosynthetic transport of CAV1. Promotes degradation of Nef cellular targets CD4 and MHC class I antigens by facilitating their trafficking to degradative compartments.

Subunit / interactions. Oligomeric complex that consists of at least the alpha, beta, beta’, gamma, delta, epsilon and zeta subunits. Interacts with SCYL1. Interacts with COPG1. Interacts (via trunk domain) with ARF1 (via switch I region); the interaction is direct. Interacts with KCNK2/TREK (via N-terminus); this interaction increases the channel-mediated whole cell currents and promotes plasma membrane expression of KCNK2/TREK. Interacts with anthrax lethal factor (LF); this interaction may facilitate endosomal vesicle membrane translocation of LF and its release from the lumen of endosomal vesicles to external milieu. Interacts with CAPN8 and PRKCE. Interacts with ARF1 (myristoylated); this interaction is required for binding of COPB1 to Golgi membranes. Interacts with STX17. Interacts with TMEM115. Interacts with HLA-G-B2M complex; this interaction mediates the endoplasmic reticulum (ER) retrieval of HLA-E-B2M complexes that bind low affinity peptides. Interacts with TMEM41B. (Microbial infection) Interacts (via C-terminus) with HIV-1 Nef; the interaction is direct.

Subcellular location. Cytoplasm. Golgi apparatus membrane. Cytoplasmic vesicle. COPI-coated vesicle membrane. Cell membrane. Endoplasmic reticulum-Golgi intermediate compartment.

Post-translational modifications. Proteolytically cleaved between Ser-528 and Ser-529 by CAPN8.

Disease relevance. Baralle-Macken syndrome (BARMACS) [MIM:619255] An autosomal recessive disorder characterized by global developmental delay, impaired intellectual development, poor or absent speech, and difficulty walking or inability to walk. Affected individuals have early-onset cataracts. Additional variable features are microcephaly, facial dysmorphism, metabolic abnormalities, spasticity, and lymphopenia. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Brefeldin A induces dissociation from the Golgi of the beta-COP and presumably the other coatomer subunits.

RefSeq proteins (3): NP_001137533, NP_001137534, NP_057535 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002553	Clathrin/coatomer_adapt-like_N	Domain
IPR011710	Coatomer_bsu_C	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR016460	COPB1	Family
IPR029446	COPB1_appendage_platform_dom	Domain

Pfam: PF01602, PF07718, PF14806

UniProt features (17 total): sequence conflict 6, repeat 6, modified residue 2, initiator methionine 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P53618-F1	82.55	0.39

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 2, 494

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic

MSigDB gene sets: 209 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, MORF_MBD4, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_SECRETORY_GRANULE, MORF_RAD21, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, MORF_PSMC2, GOBP_INTRA_GOLGI_VESICLE_MEDIATED_TRANSPORT, MORF_SKP1A, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, ATF1_Q6, BLALOCK_ALZHEIMERS_DISEASE_UP, GOCC_COATED_VESICLE, DAZARD_RESPONSE_TO_UV_SCC_UP

GO Biological Process (5): intracellular protein transport (GO:0006886), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), intra-Golgi vesicle-mediated transport (GO:0006891), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192)

GO Molecular Function (2): structural molecule activity (GO:0005198), protein binding (GO:0005515)

GO Cellular Component (19): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), Golgi apparatus (GO:0005794), Golgi-associated vesicle (GO:0005798), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), COPI vesicle coat (GO:0030126), transport vesicle (GO:0030133), secretory granule membrane (GO:0030667), tertiary granule membrane (GO:0070821), ficolin-1-rich granule membrane (GO:0101003), cytoplasm (GO:0005737), endomembrane system (GO:0012505), membrane coat (GO:0030117), COPI-coated vesicle (GO:0030137), COPI-coated vesicle membrane (GO:0030663), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Innate Immune System	1
ER to Golgi Anterograde Transport	1
Golgi-to-ER retrograde transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	6
cellular anatomical structure	4
intracellular protein localization	2
intracellular transport	2
Golgi vesicle transport	2
transport	2
Golgi apparatus	2
bounding membrane of organelle	2
intracellular membrane-bounded organelle	2
endomembrane system	2
cytoplasmic vesicle	2
secretory granule membrane	2
tertiary granule	2
protein transport	1
intercellular transport	1
establishment of protein localization	1
cellular process	1
molecular_function	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
vesicle coat	1
COPI-coated vesicle membrane	1
secretory granule	1
cytoplasmic vesicle membrane	1
ficolin-1-rich granule	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1
coated membrane	1
membrane protein complex	1
Golgi-associated vesicle	1
coated vesicle	1
COPI-coated vesicle	1
Golgi-associated vesicle membrane	1
coated vesicle membrane	1
intracellular vesicle	1

Protein interactions and networks

STRING

2372 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COPB1	COPZ1	P61923	999
COPB1	COPE	O14579	998
COPB1	COPB2	P35606	998
COPB1	ARCN1	P48444	998
COPB1	COPA	P53621	998
COPB1	COPG1	Q9Y678	993
COPB1	ARF1	P10947	943
COPB1	COG3	Q96JB2	925
COPB1	COPG2	Q9UBF2	915
COPB1	GOLPH3	Q9H4A6	890
COPB1	LMAN1	P49257	889
COPB1	KDELR1	P24390	832
COPB1	COG2	Q14746	824
COPB1	KDELR2	P33947	821
COPB1	GOLGA2	Q08379	797
COPB1	COG5	Q9UP83	797

IntAct

252 interactions, top by confidence:

A	B	Type	Score
COPG1	COPB1	psi-mi:“MI:0914”(association)	0.730
COPG1	COPB2	psi-mi:“MI:0914”(association)	0.730
CFTR	XPO1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SCYL1	SEC31A	psi-mi:“MI:0914”(association)	0.710
SPTLC1	SPTLC2	psi-mi:“MI:0914”(association)	0.680
TRIM37	COPB1	psi-mi:“MI:0915”(physical association)	0.670
HTT	COPB1	psi-mi:“MI:0915”(physical association)	0.670
COPB1	COPZ1	psi-mi:“MI:0914”(association)	0.640
COPG1	COPE	psi-mi:“MI:0914”(association)	0.640
TTYH2	COPB1	psi-mi:“MI:0915”(physical association)	0.620
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
COPB1	GTPBP4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (474): COPB1 (Affinity Capture-RNA), COPB1 (Affinity Capture-RNA), COPB1 (Affinity Capture-RNA), COPB1 (Affinity Capture-RNA), COPB1 (Affinity Capture-MS), COPB1 (Affinity Capture-MS), COPB1 (Affinity Capture-MS), TRIM37 (Two-hybrid), ACACA (Co-fractionation), COPA (Co-fractionation), COPB1 (Co-fractionation), COPB1 (Co-fractionation), COPB1 (Co-fractionation), COPB1 (Co-fractionation), COPB1 (Co-fractionation)

ESM2 similar proteins: A0JN39, A8WGF4, B5DGH9, D2SW95, O00232, O60763, O95782, P17426, P23514, P41541, P53618, P91926, P93768, Q05AY2, Q0JNK5, Q1LUA8, Q29N38, Q2KJ25, Q3B8M3, Q3UGF1, Q4R4I8, Q53PC7, Q5R4J9, Q5R664, Q5R922, Q5RBI3, Q5VQ78, Q5XI83, Q5ZIA5, Q5ZLA5, Q66HV4, Q6DRI1, Q6H8D5, Q6H8D6, Q6N069, Q6NWV3, Q6P7L9, Q7QG73, Q80UM3, Q8BWQ6

Diamond homologs: A0JN39, D2SW95, P23514, P41810, P45437, P53618, Q0JNK5, Q23924, Q29G21, Q53PC7, Q5R922, Q5ZIA5, Q66HV4, Q6FM46, Q9JIF7, Q9NFU6, Q9SV20, Q9SV21, Q9U4N3, Q9UUF7, Q9WV76, Q9LDK9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 191 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
COPI-dependent Golgi-to-ER retrograde traffic	13	11.7×	3e-08
COPI-mediated anterograde transport	13	11.6×	3e-08
Signaling by ALK fusions and activated point mutants	8	9.8×	4e-04
ER-Phagosome pathway	7	7.4×	8e-03
Cytokine Signaling in Immune system	12	4.0×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	11	23.6×	1e-09
intra-Golgi vesicle-mediated transport	7	23.5×	7e-06
endoplasmic reticulum to Golgi vesicle-mediated transport	12	10.4×	1e-06
cell surface receptor protein tyrosine kinase signaling pathway	8	8.8×	9e-04
protein autophosphorylation	8	7.4×	3e-03
intracellular protein transport	15	6.2×	7e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

134 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	92
Likely benign	13
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1678525	NM_001144061.2(COPB1):c.2102A>G (p.Gln701Arg)	Pathogenic
996037	NM_001144061.2(COPB1):c.1651T>G (p.Phe551Val)	Pathogenic

SpliceAI

3377 predictions. Top by Δscore:

Variant	Effect	Δscore
11:14458526:TGTTA:T	donor_loss	1.0000
11:14458527:GTTAC:G	donor_loss	1.0000
11:14458528:TTA:T	donor_loss	1.0000
11:14458529:TACCT:T	donor_loss	1.0000
11:14458531:C:CT	donor_loss	1.0000
11:14458531:CCTGG:C	donor_gain	1.0000
11:14458683:AGGGC:A	acceptor_gain	1.0000
11:14458684:GGGC:G	acceptor_gain	1.0000
11:14458685:GGC:G	acceptor_gain	1.0000
11:14458686:GC:G	acceptor_gain	1.0000
11:14458687:CC:C	acceptor_gain	1.0000
11:14458688:C:CC	acceptor_gain	1.0000
11:14458688:CTGG:C	acceptor_loss	1.0000
11:14460204:TTA:T	donor_loss	1.0000
11:14460205:TACC:T	donor_loss	1.0000
11:14460206:A:C	donor_loss	1.0000
11:14460207:CCT:C	donor_loss	1.0000
11:14460296:ACC:A	acceptor_loss	1.0000
11:14460299:T:C	acceptor_loss	1.0000
11:14461173:C:CA	donor_gain	1.0000
11:14461181:CTAA:C	donor_gain	1.0000
11:14461182:TAA:T	donor_loss	1.0000
11:14461183:AACT:A	donor_loss	1.0000
11:14461184:A:AC	donor_gain	1.0000
11:14461184:ACTTT:A	donor_loss	1.0000
11:14461185:C:CC	donor_gain	1.0000
11:14461185:CT:C	donor_gain	1.0000
11:14461185:CTTT:C	donor_gain	1.0000
11:14461213:CAT:C	donor_gain	1.0000
11:14461327:ATAAA:A	acceptor_gain	1.0000

AlphaMissense

6297 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:14457864:C:A	G941V	1.000
11:14457864:C:T	G941E	1.000
11:14457865:C:G	G941R	1.000
11:14457865:C:T	G941R	1.000
11:14457867:A:G	L940P	1.000
11:14457873:A:G	L938S	1.000
11:14457876:G:T	A937D	1.000
11:14457879:A:C	M936R	1.000
11:14457882:C:T	G935E	1.000
11:14457883:C:G	G935R	1.000
11:14457883:C:T	G935R	1.000
11:14458532:C:A	Q934H	1.000
11:14458532:C:G	Q934H	1.000
11:14458535:G:C	S933R	1.000
11:14458535:G:T	S933R	1.000
11:14458537:T:G	S933R	1.000
11:14458542:G:T	A931E	1.000
11:14458543:C:G	A931P	1.000
11:14458545:C:A	R930L	1.000
11:14458545:C:G	R930P	1.000
11:14458545:C:T	R930H	1.000
11:14458546:G:A	R930C	1.000
11:14458546:G:C	R930G	1.000
11:14458546:G:T	R930S	1.000
11:14458548:A:C	I929S	1.000
11:14458548:A:G	I929T	1.000
11:14458548:A:T	I929N	1.000
11:14458550:T:A	R928S	1.000
11:14458550:T:G	R928S	1.000
11:14458551:C:A	R928I	1.000

dbSNP variants (sampled 300 via entrez): RS1000041925 (11:14460680 T>G), RS1000076605 (11:14495741 A>G), RS1000121006 (11:14499499 T>C), RS1000140461 (11:14490415 G>T), RS1000195250 (11:14499783 T>C), RS1000453169 (11:14500729 A>C,T), RS1000505850 (11:14492213 T>C), RS1000680755 (11:14493783 C>T), RS1000727474 (11:14464207 A>G), RS1000742025 (11:14492506 G>A), RS1000777099 (11:14487406 G>C), RS1000808331 (11:14487645 A>G), RS1000864285 (11:14459737 C>T), RS1000923479 (11:14499025 A>T), RS1001042715 (11:14473556 G>A)

Disease associations

OMIM: gene MIM:600959 | disease phenotypes: MIM:619255, MIM:116200, MIM:300755

GenCC curated gene-disease

Disease	Classification	Inheritance
Baralle-Macken syndrome	Limited	Unknown

Mondo (5): skeletal dysplasia (MONDO:0018230), Baralle-Macken syndrome (MONDO:0031002), microcephaly (MONDO:0001149), cataract (MONDO:0005129), immunodeficiency disease (MONDO:0021094)

Orphanet (1): Primary bone dysplasia (Orphanet:364526)

HPO phenotypes

26 total (26 of 26 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000252	Microcephaly
HP:0000518	Cataract
HP:0000582	Upslanted palpebral fissure
HP:0000750	Delayed speech and language development
HP:0000956	Acanthosis nigricans
HP:0000957	Cafe-au-lait spot
HP:0001007	Hirsutism
HP:0001065	Striae distensae
HP:0001182	Tapered finger
HP:0001257	Spasticity
HP:0001319	Neonatal hypotonia
HP:0001332	Dystonia
HP:0001344	Absent speech
HP:0001513	Obesity
HP:0001763	Pes planus
HP:0002076	Migraine
HP:0002283	Global brain atrophy
HP:0002540	Inability to walk
HP:0002705	High, narrow palate
HP:0002808	Kyphosis
HP:0003593	Infantile onset
HP:0007359	Focal-onset seizure
HP:0010864	Severe intellectual disability
HP:0031936	Delayed ability to walk

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002602_7	Vitamin D levels	2.000000e-08
GCST003304_7	HDL cholesterol	2.000000e-08
GCST004232_81	HDL cholesterol levels	8.000000e-08
GCST008839_549	Height	1.000000e-47
GCST008956_2	High chromosomal aberration frequency (total)	1.000000e-06
GCST010242_363	HDL cholesterol levels	1.000000e-10
GCST90020028_1971	Hip circumference adjusted for BMI	3.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009860	chromosomal aberration frequency
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002386	Cataract	C11.510.245
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295782 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

5 potent at pChembl≥5 of 5 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.52	IC50	300	nM	MOLIBRESIB
6.09	Kd	813.3	nM	CHEMBL3752910
6.09	ED50	813.3	nM	CHEMBL3752910
6.03	Kd	927.8	nM	CHEMBL5653589
6.03	ED50	927.8	nM	CHEMBL5653589

PubChem BioAssay actives

3 with measured affinity, of 12 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178711: Inhibition of COPB1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.3000	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148115: Binding affinity to human COPB1 incubated for 45 mins by Kinobead based pull down assay	kd	0.8133	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148115: Binding affinity to human COPB1 incubated for 45 mins by Kinobead based pull down assay	kd	0.9278	uM

CTD chemical–gene interactions

41 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	2
Valproic Acid	affects expression, decreases expression	2
Cadmium Chloride	increases expression, decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization	1
arsenite	decreases reaction, affects binding	1
perfluorooctanoic acid	decreases expression	1
1-hydroxypyrene	affects cotreatment, decreases methylation	1
chloropicrin	increases expression	1
K 7174	increases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
LM11 compound	affects localization	1
bisphenol S	affects expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Furaldehyde	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118659	Binding	Binding affinity to COPB1 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00273221	PHASE4	UNKNOWN	Combined Phacotube vs Phacotrabeculectomy:A Randomized Controlled Trial
NCT00312299	PHASE4	COMPLETED	Posterior Capsule Opacification Study
NCT00345046	PHASE4	COMPLETED	A Comparison of Three Different Formulations of Prednisolone Acetate 1%
NCT00347243	PHASE4	COMPLETED	Wavefront Analisys and Contrast Sensitivity of Spherical and Aspherical Intraocular Lenses
NCT00347503	PHASE4	COMPLETED	Aqueous Concentrations and PGE2 Inhibition of Ketorolac 0.4% vs. Bromfenac 0.09% in Cataract Patients
NCT00348244	PHASE4	COMPLETED	Ketorolac vs. Steroid in the Prevention of CME
NCT00348270	PHASE4	COMPLETED	Comparison of the Quality of Vision Provided by AMO Tecnis Z9000 and Alcon Laboratories MA60 Acrysof Posterior Chamber Intraocular Lenses
NCT00348582	PHASE4	COMPLETED	Acular LS vs. Nevanac in Post op Inflammation Following Cataract Surgery
NCT00348621	PHASE4	COMPLETED	A Study of Interventions to Reduce Disability From Visual Loss in Nursing Home Residents
NCT00349583	PHASE4	COMPLETED	Efficacy of Topical Cyclosporine Versus Tears for Improving Visual Outcomes Following Multifocal IOL Implantation
NCT00355446	PHASE4	COMPLETED	Bioavailability of Bimatoprost Ophthalmic Solution in Human Aqueous.
NCT00386438	PHASE4	COMPLETED	Efficacy of Honan Balloon in Intraocular Pressure Reduction Before Phacoemulsification
NCT00392275	PHASE4	COMPLETED	Penetrance of Third Generation Fluoroquinolones in Eyes With Functioning Filtering Blebs
NCT00428363	PHASE4	COMPLETED	Effect of Optic Edge Design in a Silicone Intraocular Lens on Posterior Capsule Opacification
NCT00449267	PHASE4	COMPLETED	Aurolab Hydrophobic Foldable Intraocular Lens Study
NCT00459303	PHASE4	COMPLETED	Comparison of Functional Vision Provided by AMO Tecnis Z9000 and Alcon SA60AT Acrysof
NCT00469690	PHASE4	COMPLETED	Aqueous Concentrations and PGE2 Inhibition of Ketorolac 0.4% vs. Bromfenac 0.09% in Cataract Patients: Trough Drug Effects
NCT00576485	PHASE4	COMPLETED	Spherical Aberration and Contrast Sensitivity in IOLs
NCT00612729	PHASE4	COMPLETED	Light Filters in Intraocular Lenses (IOLs) and Its Influence on Colour and Contrast Vision.
NCT00612781	PHASE4	COMPLETED	Yellow Versus White Study
NCT00630019	PHASE4	COMPLETED	Ocular Tissue Levels of 1.5% Levofloxacin Ophthalmic Solution Compared to an Active Comparator
NCT00673803	PHASE4	COMPLETED	Influence of Two Different Preloaded Intraocular Lens (IOLs) on Posterior Capsule Opacification
NCT00684138	PHASE4	COMPLETED	ACRYSOF® ReSTOR® Aspheric +3.0 D Add Power Intraocular Lens (IOL)
NCT00698724	PHASE4	COMPLETED	Comparing Optical Coherence Tomography (OCT) and Visual Acuity Outcomes in Subjects Undergoing Cataract Surgery, Who Receive Xibrom Ophthalmic Solution and Standard Presurgical Care vs. Xibrom Ophthalmic Solution Plus Prednisolone Acetate 1% and Standard Presurgical Care
NCT00710905	PHASE4	TERMINATED	Visual Function With Contralateral AcrySof® ReSTOR® Aspheric SN6AD1 and SN6AD3
NCT00710931	PHASE4	COMPLETED	Visual Function With Bilateral AcrySof® ReSTOR® Aspheric SN6AD1
NCT00711347	PHASE4	COMPLETED	Intraoperative Floppy Iris Syndrome
NCT00712244	PHASE4	COMPLETED	DisCoVisc Versus DuoVisc, Healon5 and AmVisc Plus
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00719732	PHASE4	COMPLETED	Visual Function After Implantation of Bilateral AcrySof ReSTOR Aspheric +3
NCT00721253	PHASE4	COMPLETED	Visual Outcomes of Subjects Bilaterally Implanted With ReSTOR Aspheric +4 vs. Tecnis or Acri.LISA
NCT00731640	PHASE4	COMPLETED	Contralateral ReSTOR / Monofocal or Phakic Eye
NCT00732030	PHASE4	COMPLETED	Low Cylinder Toric
NCT00758199	PHASE4	COMPLETED	Determination of Optimum Duration of Treatment With Bromfenac (Xibrom) Eyedrops Following Cataract Surgery
NCT00760058	PHASE4	WITHDRAWN	Visual Outcome and Visual Quality After Bilateral Implantation of the AcrySof® IQ IOL Compared to MI60® and Tecnis® IOL
NCT00760487	PHASE4	COMPLETED	Visual Function After Implantation of Bilateral AcrySof® Toric Natural Intraocular Lens
NCT00761488	PHASE4	WITHDRAWN	Recommendations for Monitoring Clinical Experience Following Implantation of the AcrySof® Toric
NCT00763360	PHASE4	COMPLETED	To Compare the Ability of DiscoVisc® OVD to Protect the Corneal Endothelium and Maintain Anterior Chamber Space With Healon® and Amvisc® PLUS During Cataract Surgery.
NCT00786370	PHASE4	COMPLETED	Dexmedetomidine vs. Propofol for Cataract Surgery
NCT00786565	PHASE4	COMPLETED	Clinical Evaluation of a New Aspheric Intraocular Lens.