COPE

Summary

COPE (coat protein complex I subunit epsilon, HGNC:2234) is a protein-coding gene on chromosome 19p13.11, encoding Coatomer subunit epsilon (O14579). 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 95.2% of cancer cell lines).

The product of this gene is an epsilon subunit of coatomer protein complex. Coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles. It is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. Coatomer complex consists of at least the alpha, beta, beta’, gamma, delta, epsilon and zeta subunits. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 11316 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 72 total
• GTEx eGene: eQTL in 40 tissues, sQTL in 40 (q < 0.05)
• Cancer dependency (DepMap): dependent in 95.2% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.76 (unconstrained)
• MANE Select transcript: NM_007263
• Interaction hub: 2,163 STRING partners (top 6% of genes corpus-wide)
• Notable: 72 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2234
Approved symbol	COPE
Name	coat protein complex I subunit epsilon
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	epsilon-COP
Ensembl gene	ENSG00000105669
Ensembl biotype	protein_coding
OMIM	606942
Entrez	11316

Gene structure

Transcript identifiers

Ensembl transcripts: 73 — 41 protein_coding, 26 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000262812

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 3: 4, TSL 4: 1, TSL 5: 2

ENST00000262812, ENST00000349893, ENST00000351079, ENST00000593827, ENST00000595984, ENST00000597026, ENST00000597646, ENST00000598969, ENST00000599964, ENST00000600528, ENST00000600932, ENST00000871093, ENST00000871094, ENST00000871095, ENST00000871096, ENST00000871097, ENST00000871098, ENST00000871099, ENST00000871100, ENST00000871101, ENST00000871102, ENST00000871103, ENST00000871104, ENST00000871105, ENST00000871106, ENST00000871107, ENST00000916152, ENST00000916153, ENST00000916154, ENST00000916155, ENST00000916156, ENST00000916157, ENST00000916158, ENST00000916159, ENST00000916160, ENST00000916161, ENST00000916162, ENST00000916163, ENST00000966210, ENST00000966211, ENST00000966212, ENST00000966213, ENST00000966214, ENST00000966215, ENST00000966216, ENST00001005103, ENST00001005104, ENST00001005106, ENST00001005108, ENST00001005109, ENST00001005111, ENST00001005112, ENST00001038308, ENST00001038309, ENST00001038310, ENST00001038313, ENST00001038317, ENST00001071949, ENST00001071950, ENST00001071951, ENST00001071952, ENST00001071955, ENST00001071956, ENST00001071958, ENST00001071959, ENST00001071960, ENST00001071962, ENST00001071963, ENST00001097044, ENST00001097045, ENST00001126729, ENST00001126730, ENST00001139805

RefSeq mRNA: 4 — MANE Select: NM_007263 NM_001330469, NM_007263, NM_199442, NM_199444

CCDS: CCDS12387, CCDS12388, CCDS12389, CCDS82321

Canonical transcript exons

ENST00000262812 — 10 exons

Exon	Start	End
ENSE00000690629	18905576	18905629
ENSE00000866156	18919223	18919387
ENSE00000866168	18899514	18899726
ENSE00001113522	18906960	18907112
ENSE00003465338	18912984	18913046
ENSE00003490718	18899873	18899947
ENSE00003503486	18903268	18903423
ENSE00003540431	18900381	18900449
ENSE00003658011	18904771	18904852
ENSE00003667255	18910971	18911071

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 99.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 133.1989 / max 450.7584, expressed in 1826 samples.

Highest expression (Bgee): testis, adenohypophysis, granulocyte, endometrium epithelium, mucosa of transverse colon.

Genetic regulation across tissues (GTEx eQTL / sQTL)

COPE is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 40 tissues and its splicing (sQTL) in 40 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 80 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	1.5e-49	+1.05	19:18903439:C:T
Whole Blood	sqtl	1.6e-34	+0.85	19:18900124:GC:G
Adipose Subcutaneous	sqtl	7.9e-33	+0.86	19:18900124:GC:G
Skin Sun Exposed Lower leg	sqtl	2.4e-32	+0.95	19:18912717:C:T
Muscle Skeletal	sqtl	3.0e-28	+0.77	19:18912717:C:T
Esophagus Mucosa	sqtl	9.2e-27	+0.93	19:18903439:C:T
Lung	sqtl	3.1e-23	+0.80	19:18903439:C:T
Esophagus Muscularis	sqtl	7.8e-23	+0.91	19:18900124:GC:G
Skin Not Sun Exposed Suprapubic	sqtl	2.1e-19	+0.84	19:18900124:GC:G
Thyroid	sqtl	6.8e-19	+0.78	19:18903439:C:T
Nerve Tibial	sqtl	1.1e-18	+0.74	19:18903439:C:T
Adipose Visceral Omentum	sqtl	2.2e-18	+0.81	19:18912717:C:T
Artery Tibial	sqtl	5.6e-18	+0.74	19:18896790:G:T
Artery Aorta	sqtl	7.8e-18	+0.92	19:18896790:G:T
Stomach	sqtl	7.6e-17	+0.87	19:18903439:C:T
Thyroid	eqtl	8.5e-17	+0.14	19:18906763:T:C
Nerve Tibial	eqtl	8.8e-16	+0.13	19:18911161:T:C
Breast Mammary Tissue	sqtl	1.7e-15	+0.74	19:18903439:C:T
Heart Atrial Appendage	sqtl	4.5e-15	+0.86	19:18912717:C:T
Cells EBV-transformed lymphocytes	sqtl	1.2e-14	-0.52	19:18907053:G:A

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
180112	132.4814	1826
180108	0.4424	225
180107	0.2752	113

Top tissues by expression

showing 100 of 294 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	99.00	gold quality
left testis	UBERON:0004533	98.99	gold quality
adenohypophysis	UBERON:0002196	98.69	gold quality
granulocyte	CL:0000094	98.59	gold quality
endometrium epithelium	UBERON:0004811	98.50	gold quality
mucosa of transverse colon	UBERON:0004991	98.36	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.34	gold quality
pituitary gland	UBERON:0000007	98.32	gold quality
left adrenal gland	UBERON:0001234	98.32	gold quality
right adrenal gland	UBERON:0001233	98.31	gold quality
lower esophagus mucosa	UBERON:0035834	98.31	gold quality
left adrenal gland cortex	UBERON:0035825	98.28	gold quality
right lobe of thyroid gland	UBERON:0001119	98.20	gold quality
right adrenal gland cortex	UBERON:0035827	98.20	gold quality
left lobe of thyroid gland	UBERON:0001120	98.10	gold quality
body of stomach	UBERON:0001161	98.05	gold quality
body of pancreas	UBERON:0001150	97.96	gold quality
minor salivary gland	UBERON:0001830	97.93	gold quality
apex of heart	UBERON:0002098	97.93	gold quality
cingulate cortex	UBERON:0003027	97.93	gold quality
anterior cingulate cortex	UBERON:0009835	97.93	gold quality
testis	UBERON:0000473	97.92	gold quality
stromal cell of endometrium	CL:0002255	97.90	gold quality
monocyte	CL:0000576	97.85	gold quality
right frontal lobe	UBERON:0002810	97.85	gold quality
metanephros cortex	UBERON:0010533	97.80	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.78	gold quality
adrenal cortex	UBERON:0001235	97.76	gold quality
skin of leg	UBERON:0001511	97.71	gold quality
prefrontal cortex	UBERON:0000451	97.69	gold quality
amygdala	UBERON:0001876	97.68	gold quality
spinal cord	UBERON:0002240	97.68	gold quality
transverse colon	UBERON:0001157	97.67	gold quality
nucleus accumbens	UBERON:0001882	97.67	gold quality
leukocyte	CL:0000738	97.64	gold quality
ectocervix	UBERON:0012249	97.63	gold quality
mononuclear cell	CL:0000842	97.61	gold quality
left coronary artery	UBERON:0001626	97.61	gold quality
adrenal gland	UBERON:0002369	97.59	gold quality
lower esophagus	UBERON:0013473	97.58	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.58	gold quality
endocervix	UBERON:0000458	97.57	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.57	gold quality
upper lobe of left lung	UBERON:0008952	97.56	gold quality
right lobe of liver	UBERON:0001114	97.54	gold quality
skin of abdomen	UBERON:0001416	97.54	gold quality
right atrium auricular region	UBERON:0006631	97.54	gold quality
spleen	UBERON:0002106	97.52	gold quality
ascending aorta	UBERON:0001496	97.51	gold quality
caudate nucleus	UBERON:0001873	97.51	gold quality
thyroid gland	UBERON:0002046	97.51	gold quality
thoracic aorta	UBERON:0001515	97.50	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.49	gold quality
left uterine tube	UBERON:0001303	97.46	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.46	gold quality
middle frontal gyrus	UBERON:0002702	97.44	gold quality
ganglionic eminence	UBERON:0004023	97.43	gold quality
esophagus	UBERON:0001043	97.36	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.31	gold quality
putamen	UBERON:0001874	97.26	gold quality
hypothalamus	UBERON:0001898	97.24	gold quality
coronary artery	UBERON:0001621	97.23	gold quality
small intestine	UBERON:0002108	97.23	gold quality
esophagus mucosa	UBERON:0002469	97.22	gold quality
aorta	UBERON:0000947	97.19	gold quality
right coronary artery	UBERON:0001625	97.18	gold quality
mucosa of stomach	UBERON:0001199	97.17	gold quality
descending thoracic aorta	UBERON:0002345	97.15	gold quality
body of uterus	UBERON:0009853	97.15	gold quality
upper lobe of lung	UBERON:0008948	97.14	gold quality
cortical plate	UBERON:0005343	97.12	gold quality
saliva-secreting gland	UBERON:0001044	97.11	gold quality
paraflocculus	UBERON:0005351	97.10	gold quality
popliteal artery	UBERON:0002250	97.05	gold quality
tibial artery	UBERON:0007610	97.05	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.04	gold quality
right lung	UBERON:0002167	97.01	gold quality
right ovary	UBERON:0002118	96.99	gold quality
mouth mucosa	UBERON:0003729	96.98	gold quality
stomach	UBERON:0000945	96.96	gold quality
right uterine tube	UBERON:0001302	96.96	gold quality
omental fat pad	UBERON:0010414	96.91	gold quality
peritoneum	UBERON:0002358	96.86	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.86	gold quality
tibial nerve	UBERON:0001323	96.83	gold quality
cardiac atrium	UBERON:0002081	96.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.80	gold quality
bone marrow cell	CL:0002092	96.70	gold quality
heart left ventricle	UBERON:0002084	96.66	gold quality
frontal pole	UBERON:0002795	96.60	gold quality
cerebellar cortex	UBERON:0002129	96.54	gold quality
cerebellar hemisphere	UBERON:0002245	96.53	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.52	gold quality
left ovary	UBERON:0002119	96.47	gold quality
cardiac ventricle	UBERON:0002082	96.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.43	gold quality
colon	UBERON:0001155	96.41	gold quality
sigmoid colon	UBERON:0001159	96.39	gold quality
embryo	UBERON:0000922	96.28	gold quality
gastrocnemius	UBERON:0001388	96.28	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	3730.76
E-GEOD-124263	yes	1933.97
E-HCAD-1	yes	43.39
E-CURD-122	yes	24.41
E-CURD-46	yes	21.31
E-HCAD-9	yes	19.63
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Pituitary gland	tissue	156.5
Bone marrow	tissue	150.5	medium
Salivary gland	tissue	135.8	high
Choroid plexus	tissue	117.8
Locus coeruleus	tissue	111.9
Vagina	tissue	103.9	medium
Frontal cortex	tissue	102.8
Spinal cord	tissue	100.4
Nucleus accumbens	tissue	98.3
Hippocampus	tissue	97.4	low
Midbrain	tissue	93.9
Pancreas	tissue	93.2	high
Medulla oblongata	tissue	91.0
Thalamus	tissue	89.3
Substantia nigra	tissue	86.3
Lymph node	tissue	85.8
Pons	tissue	85.7
Duodenum	tissue	85.1	medium
Superior colliculi	tissue	84.0
Small intestine	tissue	83.3	high
Caudate putamen	tissue	82.5
Appendix	tissue	80.6	medium
Thymus	tissue	76.8
Parathyroid gland	tissue	75.9	medium
Corpus callosum	tissue	75.2
Postcentral gyrus	tissue	74.5
Adrenal gland	tissue	73.8	medium
Stomach 1	tissue	73.6	medium
Heart muscle	tissue	72.2	not detected
Hypothalamus	tissue	71.0
Hippocampal formation	tissue	69.8
Skeletal muscle	tissue	69.7	not detected
Periaqueductal gray	tissue	67.4
Colon	tissue	67.3	medium
Esophagus	tissue	65.7	medium
Spleen	tissue	64.7	low
Putamen	tissue	62.1
Seminal vesicle	tissue	61.6	medium
Thyroid gland	tissue	61.2	medium
Cerebral cortex	tissue	60.5	medium
Somatosensory cortex	tissue	60.5
Testis	tissue	59.6	medium
Septum	tissue	59.3
Liver	tissue	59.1	medium
Cervix	tissue	58.9	medium
Prostate	tissue	58.3	medium
Ventral forebrain	tissue	56.1
Placenta	tissue	55.7	medium
Skin 1	tissue	54.9	low
Motor cortex	tissue	54.8
Urinary bladder	tissue	54.7	medium
Tonsil	tissue	53.3	medium
Ovary	tissue	52.9	not detected
Adipose tissue	tissue	52.9	not detected
Entorhinal cortex	tissue	52.9
Prefrontal cortex	tissue	52.2
Temporal cortex	tissue	52.0
Fallopian tube	tissue	51.7	medium
Occipital cortex	tissue	51.1
Basal ganglia	tissue	50.7	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Dorsal funiculus (white matter) (156.1), Lateral funiculus (white matter) (149.0), Nucleus ambiguus (138.0), Cerebellar nuclei (134.7), Anterior funiculus (white matter) (134.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting COPE by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

9 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-3620-3P	97.78	64.88	772
HSA-MIR-4653-3P	96.26	67.03	725

Functional genomics

gnomAD constraint: pLI 0.00191, LOEUF 0.764, missense Z -0.179 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000262812 — one region, missense o/e 0.97. DepMap (CRISPR cell-line fitness): dependent in 95.2% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): NCI-H2052 (-2.746), SW837 (-2.163), AsPC-1 (-2.091), KP-3 (-2.089), SNU-1105 (-2.062), SNU-449 (-2.047), RT4 (-2.017), SLR 24 (-1.92), SW 1088 (-1.911), SK-N-MC (-1.908), HCC-827-GR5 (-1.879), TE-5 (-1.878), SNU-1079 (-1.872), RD (-1.845), LOU-NH91 (-1.839).

Literature-anchored findings (GeneRIF, showing 2)

• Ubiquitylation of epsilon-COP by PIRH2; overexpression of the wild type of PIRH2 in prostate cancer cells causes downregulation of the secretion of prostate-specific antigen. (PMID:17721809)
• Data show that iPLA(1)gamma is a novel membrane transport factor that contributes to a specific Golgi-to-ER retrograde pathway distinct from presently characterized COPI- and Rab6-dependent pathways. (PMID:19632984)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cope	ENSDARG00000018562
mus_musculus	Cope	ENSMUSG00000055681
rattus_norvegicus	Cope	ENSRNOG00000020178
drosophila_melanogaster	epsilonCOP	FBGN0027496
caenorhabditis_elegans		WBGENE00009732

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RFR8	99.4%	Diamond
Oryza sativa Indica Group	A2XY73	99.3%	Diamond
Oryza sativa Japonica Group	P0C541	99.3%	Diamond
Cricetulus griseus	Q60445	95.8%	Diamond
Bos taurus	Q28104	94.2%	Diamond
Arabidopsis thaliana	Q9SA78	88.1%	Diamond
Gallus gallus	Q5ZIK9	83.9%	Diamond
Dictyostelium discoideum	Q55FU2	37.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SUGP2	protein-coding	10147
DDX49	protein-coding	54555
ARMC6	protein-coding	93436
HOMER3	protein-coding	9454
COMP	protein-coding	1311
GDF1	protein-coding	2657
UPF1	protein-coding	5976
CERS1	protein-coding	10715
CRTC1	protein-coding	23373
HOMER3-AS1	ncRNA	102724360

Protein

Protein identifiers

Coatomer subunit epsilon — O14579 (reviewed: O14579)

Alternative names: Epsilon-coat protein

All UniProt accessions (3): O14579, M0QXB4, M0R061

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. The 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 with 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.

Subunit / interactions. Oligomeric complex that consists of at least the alpha, beta, beta’, gamma, delta, epsilon and zeta subunits.

Subcellular location. Cytoplasm. Golgi apparatus membrane. Cytoplasmic vesicle. COPI-coated vesicle membrane.

Post-translational modifications. Phosphorylated by PKA. Polyubiquitinated by RCHY1 in the presence of androgen, leading to proteasomal degradation.

Similarity. Belongs to the COPE family.

Isoforms (3)

UniProt ID	Names	Canonical?
O14579-1	1	yes
O14579-2	2
O14579-3	3

RefSeq proteins (4): NP_001317398, NP_009194, NP_955474, NP_955476 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006822	Coatomer_esu	Family
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily

Pfam: PF04733

UniProt features (29 total): helix 18, modified residue 3, splice variant 3, sequence variant 2, initiator methionine 1, chain 1, turn 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
6U3V	Crystal structure of human alpha/epsilon-COP of the COPI vesicular coat bound to …	X-RAY DIFFRACTION	2.96
6TZT	Crystal structure of human alpha/epsilon-COP of the COPI vesicular coat bound to …	X-RAY DIFFRACTION	3.06

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14579-F1	90.20	0.78

Human Protein Atlas

Protein class: Metabolic proteins, Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus

Antibody reliability (HPA): IH supported · IF enhanced

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 (3)

Type	Positions
Phosphoserine	13, 45, 99

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

ID	Pathway	Evidence
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic	curated
R-HSA-6807878	COPI-mediated anterograde transport	curated
R-HSA-446203	Asparagine N-linked glycosylation	—
R-HSA-199977	ER to Golgi Anterograde Transport	—
R-HSA-8856688	Golgi-to-ER retrograde transport	—
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic	—
R-HSA-199991	Membrane Trafficking	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-948021	Transport to the Golgi and subsequent modification	—
R-HSA-5653656	Vesicle-mediated transport	—

MSigDB gene sets: 155 (showing top): MODULE_255, ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_HDAC1, MODULE_317, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_INTRA_GOLGI_VESICLE_MEDIATED_TRANSPORT, MORF_SKP1A, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, GROSS_ELK3_TARGETS_DN, GOCC_COATED_VESICLE, GOCC_GOLGI_ASSOCIATED_VESICLE, GOCC_VESICLE_COAT, MORF_GPX4, MODULE_207

GO Biological Process (5): endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), 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 (10): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cytosol (GO:0005829), COPI vesicle coat (GO:0030126), transport vesicle (GO:0030133), cytoplasm (GO:0005737), COPI-coated vesicle (GO:0030137), COPI-coated vesicle membrane (GO:0030663), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Membrane Trafficking	2
ER to Golgi Anterograde Transport	1
Golgi-to-ER retrograde transport	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Post-translational protein modification	1
Metabolism of proteins	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Asparagine N-linked glycosylation	1

GO top-level categories

27 GO namespaces:

Category	Terms
cytoplasm	4
Golgi vesicle transport	3
transport	2
Golgi apparatus	2
endomembrane system	2
cellular anatomical structure	2
intracellular transport	1
intracellular protein localization	1
establishment of protein localization	1
cellular process	1
molecular_function	1
binding	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular membrane-bounded organelle	1
vesicle coat	1
COPI-coated vesicle membrane	1
cytoplasmic vesicle	1
intracellular anatomical structure	1
Golgi-associated vesicle	1
coated vesicle	1
COPI-coated vesicle	1
Golgi-associated vesicle membrane	1
coated vesicle membrane	1
intracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
Golgi apparatus	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 2,163 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COPE	COPA	P53621	971
COPE	COPZ1	P61923	965
COPE	ARCN1	P48444	957
COPE	COPB2	P35606	952
COPE	COPB1	P53618	929
COPE	SEC13	P55735	639
COPE	ARF1	P10947	634
COPE	COPG1	Q9Y678	632
COPE	COPG2	Q9UBF2	549
COPE	RER1	O15258	485
COPE	COPZ2	Q9P299	483
COPE	SH3GLB2	Q9NR46	476
COPE	PREB	Q9HCU5	454
COPE	GOLPH3	Q9H4A6	445
COPE	COPRS	Q9NQ92	437

IntAct

Human interaction partners of COPE in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

21 partners by confidence:

Partner	Interaction type	MIscore	Records
EFHC2	physical association	0.720	6
COPG1	association	0.640	3
SACM1L	association	0.640	1
CDC42EP3	physical association	0.560	3
COPZ1	association	0.530	2
COPB2	association	0.530	1
PPM1G	association	0.530	1
MBD1	physical association	0.370	1
TSG101	physical association	0.370	1
E7	association	0.350	2
S	association	0.350	2
ATP6AP2	association	0.350	1
COPZ2	association	0.350	1
ESYT2	association	0.350	1
HSD17B10	association	0.350	1
NGEF	association	0.350	1
RHOG	association	0.350	1
SMARCAL1	association	0.350	1
STAT3	proximity	0.270	1
CASP4	physical association	0.000	1
COPA	physical association	0.000	1

BioGRID (454 interactions; top human partners by supporting records): COPA (Co-fractionation; 15 records), COPG1 (Co-fractionation; 11 records), COPB1 (Affinity Capture-MS; 7 records), COPB2 (Two-hybrid; 6 records), COPG2 (Co-fractionation; 6 records), ARCN1 (Co-fractionation; 4 records), BAP1 (Affinity Capture-MS; 4 records), COPZ1 (Affinity Capture-MS; 4 records), SACM1L (Affinity Capture-MS; 4 records), NUDCD1 (Affinity Capture-MS; 3 records), RCHY1 (Two-hybrid; 3 records), SCYL1 (Negative Genetic; 3 records), TGOLN2 (Affinity Capture-MS; 3 records), ATL2 (Affinity Capture-MS; 2 records), BAG3 (Affinity Capture-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
RCHY1	“down-regulates quantity by destabilization”	COPE	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 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	5	34.6×	1e-05
COPI-mediated anterograde transport	5	34.3×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
intra-Golgi vesicle-mediated transport	5	138.6×	4e-08
intracellular protein transport	5	17.1×	6e-04

Disease & clinical

Genetic variants

Variant evidence for COPE: 72 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 934):

Position(s)	Effect	Δscore	Sites
19:18899872	donor_loss	1.0000	3
19:18899948–18899949	acceptor_loss	1.0000	6
19:18900379–18900380	donor_loss	1.0000	3
19:18900450–18900451	acceptor_loss	1.0000	6
19:18900460	acceptor_gain	1.0000
19:18903267	donor_loss	1.0000
19:18903424–18903425	acceptor_loss	1.0000	6
19:18904853–18904854	acceptor_loss	1.0000	5
19:18904860	acceptor_gain	1.0000
19:18906958–18906959	donor_loss	1.0000	5

AlphaMissense

690 missense substitutions predicted likely pathogenic (of 2,013 scored), across 210 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D178	8	0.968	0.993
D163	8	0.906	0.959
F297	8	0.839	0.973
D176	8	0.781	0.908
D17	8	0.737	0.905
D279	8	0.677	0.903
F20	7	0.953	0.991
F205	7	0.946	0.981
M172	7	0.937	0.989
N255	7	0.910	0.995
F26	7	0.895	0.978
E147	7	0.881	0.983
W188	7	0.840	0.985
R58	6	0.951	0.992
R161	6	0.949	0.998
G29	6	0.890	0.993
K211	6	0.883	0.962
K65	6	0.870	0.947
K265	6	0.863	0.960
C34	6	0.859	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000385
Uterine Corpus Endometrial Carcinoma (TCGA)	favorable	0.000477

Disease associations

OMIM: gene MIM:606942 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067056 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.90	Kd	126.2	nM	CHEMBL5653589
6.90	ED50	126.2	nM	CHEMBL5653589
6.10	Kd	786.7	nM	CHEMBL3752910
6.10	ED50	786.7	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148117: Binding affinity to human COPE incubated for 45 mins by Kinobead based pull down assay	kd	0.1262	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148117: Binding affinity to human COPE incubated for 45 mins by Kinobead based pull down assay	kd	0.7867	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression	4
Cyclosporine	increases expression	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	3
cobaltous chloride	decreases expression	2
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
tetrabromobisphenol A	decreases expression	1
bufalin	decreases expression	1
coumarin	increases phosphorylation	1
ICG 001	decreases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Vehicle Emissions	increases expression	1
Caffeine	increases phosphorylation	1
Dinitrochlorobenzene	affects binding	1
Gasoline	increases expression, affects cotreatment, increases abundance	1
Hydralazine	increases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Polycyclic Aromatic Hydrocarbons	increases abundance, increases expression, affects cotreatment	1
Quercetin	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651159	Binding	Binding affinity to human COPE incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for COPE across ~30M SureChEMBL compounds — explore on Sugi Predict.