COPA

Summary

COPA (coat protein complex I subunit alpha, HGNC:2230) is a protein-coding gene on chromosome 1q23.2, encoding Coatomer subunit alpha (P53621). 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).

In eukaryotic cells, protein transport between the endoplasmic reticulum and Golgi compartments is mediated in part by non-clathrin-coated vesicular coat proteins (COPs). Seven coat proteins have been identified, and they represent subunits of a complex known as coatomer. The subunits are designated alpha-COP, beta-COP, beta-prime-COP, gamma-COP, delta-COP, epsilon-COP, and zeta-COP. The alpha-COP, encoded by COPA, shares high sequence similarity with RET1P, the alpha subunit of the coatomer complex in yeast. Also, the N-terminal 25 amino acids of alpha-COP encode the bioactive peptide, xenin, which stimulates exocrine pancreatic secretion and may act as a gastrointestinal hormone. Alternative splicing results in multiple splice forms encoding distinct isoforms.

Source: NCBI Gene 1314 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autoimmune interstitial lung disease-arthritis syndrome (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 1,032 total — 5 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 17
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_004371

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2230
Approved symbol	COPA
Name	coat protein complex I subunit alpha
Location	1q23.2
Locus type	gene with protein product
Status	Approved
Aliases	HEP-COP, alpha-COP
Ensembl gene	ENSG00000122218
Ensembl biotype	protein_coding
OMIM	601924
Entrez	1314

Gene structure

Transcript identifiers

Ensembl transcripts: 50 — 22 protein_coding, 21 retained_intron, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000241704, ENST00000368069, ENST00000481040, ENST00000481522, ENST00000541366, ENST00000545266, ENST00000545284, ENST00000647683, ENST00000647693, ENST00000647799, ENST00000647899, ENST00000648280, ENST00000648501, ENST00000648632, ENST00000648805, ENST00000649231, ENST00000649676, ENST00000649787, ENST00000649963, ENST00000650154, ENST00000696202, ENST00000696203, ENST00000696204, ENST00000696205, ENST00000696206, ENST00000696207, ENST00000696208, ENST00000696209, ENST00000696210, ENST00000696211, ENST00000696212, ENST00000696213, ENST00000696214, ENST00000696215, ENST00000696216, ENST00000890164, ENST00000890165, ENST00000911817, ENST00000911818, ENST00000911819, ENST00000911820, ENST00000971414, ENST00000971415, ENST00000971416, ENST00000971417, ENST00000971418, ENST00000971419, ENST00000971420, ENST00000971421, ENST00000971422

RefSeq mRNA: 2 — MANE Select: NM_004371 NM_001098398, NM_004371

CCDS: CCDS1202, CCDS41424

Canonical transcript exons

ENST00000241704 — 33 exons

Exon	Start	End
ENSE00000905036	160305433	160305571
ENSE00000905037	160305688	160305773
ENSE00000905038	160306354	160306493
ENSE00000905039	160307163	160307245
ENSE00000905040	160309101	160309176
ENSE00000905041	160310192	160310258
ENSE00000905042	160311868	160312018
ENSE00000905043	160313085	160313167
ENSE00000905044	160313990	160314125
ENSE00000905045	160323431	160323530
ENSE00000905046	160325543	160325652
ENSE00000905047	160332448	160332557
ENSE00000905048	160333603	160333679
ENSE00001040295	160299102	160299264
ENSE00001068108	160292484	160292620
ENSE00001068109	160294768	160294857
ENSE00001068110	160291335	160291496
ENSE00001068111	160291819	160291929
ENSE00001068113	160343131	160343250
ENSE00001068114	160293166	160293234
ENSE00001068116	160294484	160294593
ENSE00001068117	160292012	160292198
ENSE00001068119	160293386	160293463
ENSE00001068120	160290492	160290686
ENSE00003486516	160295736	160295859
ENSE00003553776	160335242	160335322
ENSE00003556799	160297556	160297745
ENSE00003574294	160298845	160298991
ENSE00003611022	160339909	160339982
ENSE00003632164	160296061	160296149
ENSE00003658913	160340181	160340294
ENSE00003679629	160297343	160297438
ENSE00003856161	160288594	160290216

Expression profiles

Bgee: expression breadth ubiquitous, 303 present calls, max score 98.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 72.1256 / max 1130.1496, expressed in 1826 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15496	63.9548	1826
15495	8.1708	1714

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	98.71	gold quality
islet of Langerhans	UBERON:0000006	98.38	gold quality
pituitary gland	UBERON:0000007	98.01	gold quality
ganglionic eminence	UBERON:0004023	97.94	gold quality
adenohypophysis	UBERON:0002196	97.87	gold quality
inferior vagus X ganglion	UBERON:0005363	97.87	gold quality
cartilage tissue	UBERON:0002418	97.74	gold quality
corpus callosum	UBERON:0002336	97.68	gold quality
smooth muscle tissue	UBERON:0001135	97.60	gold quality
pylorus	UBERON:0001166	97.52	gold quality
adrenal tissue	UBERON:0018303	97.25	gold quality
cardia of stomach	UBERON:0001162	97.22	gold quality
rectum	UBERON:0001052	97.20	gold quality
descending thoracic aorta	UBERON:0002345	97.20	gold quality
ventricular zone	UBERON:0003053	97.18	gold quality
monocyte	CL:0000576	97.17	gold quality
thoracic aorta	UBERON:0001515	97.13	gold quality
ascending aorta	UBERON:0001496	97.12	gold quality
right ovary	UBERON:0002118	97.11	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.11	gold quality
upper lobe of left lung	UBERON:0008952	97.11	gold quality
endocervix	UBERON:0000458	97.10	gold quality
upper lobe of lung	UBERON:0008948	97.10	gold quality
mononuclear cell	CL:0000842	97.05	gold quality
right coronary artery	UBERON:0001625	97.00	gold quality
body of pancreas	UBERON:0001150	96.99	gold quality
leukocyte	CL:0000738	96.96	gold quality
right lobe of thyroid gland	UBERON:0001119	96.95	gold quality
left ovary	UBERON:0002119	96.95	gold quality
jejunal mucosa	UBERON:0000399	96.94	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-112	no	2.37
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

79 targeting COPA, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4699-3P	99.71	70.15	3142

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 20)

• Among ten hepatocellular carcinoma cases with amplicon 1q21-q22, significant gene expression level of JTB, SHC1, CCT3 and COPA in the tumors than the paired adjacent non-malignant liver tissues. (PMID:12586295)
• These results suggested that Yip1A has a role in COPI-independent retrograde transport from the Golgi to the ER and regulates the membrane recruitment of Rab6. (PMID:19509059)
• SMN directly binds to COPI and moves with survival motor neuron within axons. (PMID:21300694)
• Electron tomography reveals Rab6 is essential to the trafficking of trans-Golgi clathrin and COPI-coated vesicles and the maintenance of Golgi cisternal number (PMID:22335553)
• Compared with day workers within the same BMI range, night workers presented a disrupted control of ghrelin and xenin, associated with behavioural changes in diet and sleep and increased adiposity and related metabolic alterations. (PMID:23199168)
• Results show that the interaction between SMN and alpha-COP serves an important function in the growth and maintenance of motor neuron processes and may play a significant role in the pathogenesis of Spinal muscular atrophy. (PMID:23727837)
• The cell membrane gene SLC4A4 and the trafficking regulator gene COPA, which also plays an important role in early endosome maturation, were identified for the cellular entry of poly-arginine peptide. (PMID:24489756)
• Serum xenin levels of obese patients were higher than in control groups. (PMID:25200997)
• COPA variants impair binding to proteins targeted for retrograde Golgi-to-ER transport. (PMID:25894502)
• This is the second report of a pathogenic mutation in COPA. The p.Glu241Lys mutation detected in the current Icelandic pedigree is a de novo mutation. The fact that the mutation is absent from 176,040 unrelated individuals but present in two families with affected individuals confirms its role in the pathogenesis of COPA syndrome. (PMID:29137621)
• Reduced RNA editing of COPA gene is associated with psoriasis. (PMID:29592874)
• COPI facilitated dengue virus (DENV) production in an endothelial cell line and in all DENV serotypes, indicating the importance of coat protein complex in facilitating DENV infection. (PMID:29608995)
• knockdown of COPA caused increased expression of viral late genes despite substantial inhibition of viral DNA replication. (PMID:29946045)
• Loss of RAB6-interacting golgin (GORAB) causes impairment of coat protein complex I (COPI)-mediated retrieval of trans-Golgi enzymes, resulting in a deficit in glycosylation of secretory cargo proteins. (PMID:30631079)
• median serum levels elevated in polycystic ovary syndrome (PMID:31010340)
• Hazara Nairovirus Requires COPI Components in both Arf1-Dependent and Arf1-Independent Stages of Its Replication Cycle. (PMID:32581103)
• A Zebra at the Rodeo: Dyspnea, Hematuria, and a Family History of Arthritis. (PMID:32598558)
• Mutations in COPA lead to abnormal trafficking of STING to the Golgi and interferon signaling. (PMID:32725128)
• An extended motif in the SARS-CoV-2 spike modulates binding and release of host coatomer in retrograde trafficking. (PMID:35136165)
• Heterozygous mutations in the C-terminal domain of COPA underlie a complex autoin fl ammatory syndrome. (PMID:38175705)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	copa	ENSDARG00000004173
mus_musculus	Copa	ENSMUSG00000026553
rattus_norvegicus	Copa	ENSRNOG00000006247
drosophila_melanogaster	alphaCOP	FBGN0025725
caenorhabditis_elegans	copa-1	WBGENE00022119

Paralogs (1): COPB2 (ENSG00000184432)

Protein

Protein identifiers

Coatomer subunit alpha — P53621 (reviewed: P53621)

Alternative names: Alpha-coat protein, HEP-COP

All UniProt accessions (12): A0A3B3IS23, A0A3B3IS84, A0A3B3ISC6, A0A3B3ISK1, A0A3B3IT15, A0A3B3ITI7, A0A3B3ITV3, A0A3B3ITX2, A0A3B3IU78, A0A3B3IU84, A0A3B3IU89, P53621

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. Xenin stimulates exocrine pancreatic secretion. It inhibits pentagastrin-stimulated secretion of acid, to induce exocrine pancreatic secretion and to affect small and large intestinal motility. In the gut, xenin interacts with the neurotensin receptor.

Subunit / interactions. Oligomeric complex that consists of at least the alpha, beta, beta’, gamma, delta, epsilon and zeta subunits. Interacts with SCYL1. Interacts with JAGN1. Interacts with TMEM41B. Interacts with SVEP1. Probably interacts with PEX11A.

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

Tissue specificity. Uniformly expressed in a wide range of adult and fetal tissues. Xenin is found in gastric, duodenal and jejunal mucosa. Circulates in the blood. Seems to be confined to specific endocrine cells.

Disease relevance. Autoinflammation and autoimmunity, systemic, with immune dysregulation (AIAISD) [MIM:616414] An autoinflammatory disorder with systemic manifestations. Clinical features include inflammatory arthritis, interstitial lung disease, alveolar hemorrhage, neuromyelitis optica, and immune complex-mediated renal disease. AIAISD inheritance is autosomal dominant with incomplete penetrance. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
P53621-1	1	yes
P53621-2	2

RefSeq proteins (2): NP_001091868, NP_004362* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR006692	Beta-prop_COPA/B_2nd	Domain
IPR010714	Coatomer_asu_C	Domain
IPR011048	Haem_d1_sf	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016391	Coatomer_asu	Family
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR047312	Coatomer_alpha_WD-assoc_reg	Domain
IPR050844	Coatomer_complex_subunit	Family
IPR056176	TPR_COPA_B	Domain

Pfam: PF00400, PF04053, PF06957, PF23953

UniProt features (85 total): strand 36, helix 17, modified residue 7, turn 7, repeat 7, sequence variant 6, peptide 2, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6PBG	X-RAY DIFFRACTION	1.72
6U3V	X-RAY DIFFRACTION	2.96
6TZT	X-RAY DIFFRACTION	3.06

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P53621-F1	83.85	0.46

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 (7): 173, 185, 402, 591, 895, 965, 1193

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

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

MSigDB gene sets: 216 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_DIGESTION, ELVIDGE_HYPOXIA_DN, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, HSIAO_HOUSEKEEPING_GENES, LANG_MYB_FAMILY_TARGETS, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_INTRA_GOLGI_VESICLE_MEDIATED_TRANSPORT, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, GOCC_COATED_VESICLE

GO Biological Process (10): intracellular protein transport (GO:0006886), 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), pancreatic juice secretion (GO:0030157), protein localization to axon (GO:0099612), protein localization to cell leading edge (GO:1902463), signal transduction (GO:0007165), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192)

GO Molecular Function (4): mRNA binding (GO:0003729), hormone activity (GO:0005179), structural molecule activity (GO:0005198), protein binding (GO:0005515)

GO Cellular Component (16): Golgi membrane (GO:0000139), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), membrane (GO:0016020), COPI vesicle coat (GO:0030126), transport vesicle (GO:0030133), growth cone (GO:0030426), extracellular exosome (GO:0070062), extracellular region (GO:0005576), Golgi apparatus (GO:0005794), 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-2 pathways:

Category	Pathways
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	5
intracellular protein localization	4
cellular anatomical structure	4
Golgi vesicle transport	3
intracellular transport	2
cellular process	2
transport	2
Golgi apparatus	2
endomembrane system	2
protein transport	1
intercellular transport	1
body fluid secretion	1
digestive system process	1
secretion by tissue	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
establishment of protein localization	1
RNA binding	1
receptor ligand activity	1
molecular_function	1
binding	1
bounding membrane of organelle	1
intracellular anatomical structure	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
vesicle coat	1
COPI-coated vesicle membrane	1
cytoplasmic vesicle	1
site of polarized growth	1
distal axon	1
extracellular vesicle	1
intracellular membrane-bounded organelle	1
coated membrane	1
membrane protein complex	1
Golgi-associated vesicle	1
coated vesicle	1
COPI-coated vesicle	1

Protein interactions and networks

STRING

1679 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COPA	ARCN1	P48444	999
COPA	COPE	O14579	999
COPA	COPB1	P53618	998
COPA	COPZ1	P61923	998
COPA	COPB2	P35606	979
COPA	COPG1	Q9Y678	761
COPA	GOLPH3	Q9H4A6	739
COPA	NTSR1	P30989	704
COPA	NTSR2	O95665	681
COPA	ARF1	P10947	671
COPA	VSX2	P58304	643
COPA	NTS	P30990	609
COPA	SEC13	P55735	607
COPA	SURF4	O15260	597
COPA	SMN1	Q16637	597

IntAct

222 interactions, top by confidence:

A	B	Type	Score
COPG1	COPB2	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
E7	RB1	psi-mi:“MI:0914”(association)	0.700
SPTLC1	SPTLC2	psi-mi:“MI:0914”(association)	0.680
COPG1	COPE	psi-mi:“MI:0914”(association)	0.640
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
Copa	COPE	psi-mi:“MI:0915”(physical association)	0.560
FOXR1	MYC	psi-mi:“MI:0914”(association)	0.530
MTNR1B	IRS4	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
	XPO1	psi-mi:“MI:0914”(association)	0.530
PPM1G	COPE	psi-mi:“MI:0914”(association)	0.530
TMED9	COPB2	psi-mi:“MI:0914”(association)	0.530
COPZ1	COPE	psi-mi:“MI:0914”(association)	0.530
COPE	COPB2	psi-mi:“MI:0914”(association)	0.530
CEMIP	COPA	psi-mi:“MI:0914”(association)	0.500
CEMIP	COPA	psi-mi:“MI:0915”(physical association)	0.500
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (605): COPA (Affinity Capture-RNA), COPA (Affinity Capture-RNA), COPA (Affinity Capture-RNA), COPA (Affinity Capture-MS), COPA (Affinity Capture-MS), COPA (Affinity Capture-MS), COPA (Affinity Capture-MS), COPA (Affinity Capture-MS), COPA (Affinity Capture-MS), COPA (Affinity Capture-RNA), CCDC97 (Co-fractionation), COPA (Co-fractionation), COPA (Co-fractionation), COPA (Co-fractionation), COPA (Co-fractionation)

ESM2 similar proteins: A0A0F8V8L2, A0A0F8VPX6, A0A0F8XMN8, A0A1Q9P359, A0A7H0DND9, A8Q8M5, B0G186, B3DL37, B8QYR5, C6Y4A8, O57243, P0C9A2, P0C9A3, P0C9A4, P0C9B4, P0C9B5, P0C9B6, P0DSW5, P0DSW6, P34392, P53621, P68695, P86294, P87054, Q0J3D9, Q10271, Q10436, Q27954, Q3E830, Q3E841, Q4N927, Q5RJW4, Q65181, Q65224, Q6RZE1, Q76ZN5, Q775N7, Q77DS0, Q77TH1, Q80DT4

Diamond homologs: P40765, P41811, P53621, P53622, Q0J3D9, Q27954, Q55FR9, Q5VQ78, Q8CIE6, Q94A40, Q96WV5, Q9AUR7, Q9AUR8, Q9SJT9, A0DB19

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 210 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	12	9.8×	3e-06
Defective CFTR causes cystic fibrosis	6	9.7×	1e-02
COPI-mediated anterograde transport	11	8.9×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
intra-Golgi vesicle-mediated transport	6	18.5×	5e-04
cellular response to nerve growth factor stimulus	6	16.4×	7e-04
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	8	15.8×	5e-05
peptidyl-tyrosine phosphorylation	5	12.3×	9e-03
endoplasmic reticulum to Golgi vesicle-mediated transport	9	7.2×	2e-03
response to ethanol	8	6.9×	5e-03
protein autophosphorylation	8	6.8×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1032 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	2
Uncertain significance	416
Likely benign	449
Benign	47

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1013258	NM_004371.4(COPA):c.718T>C (p.Trp240Arg)	Pathogenic
199256	NM_004371.4(COPA):c.721G>A (p.Glu241Lys)	Pathogenic
218941	NM_004371.4(COPA):c.690G>T (p.Lys230Asn)	Pathogenic
3370278	NM_004371.4(COPA):c.3424C>T (p.Arg1142Ter)	Pathogenic
577775	NM_004371.4(COPA):c.715G>C (p.Ala239Pro)	Pathogenic
1526108	NM_004371.4(COPA):c.725T>C (p.Val242Ala)	Likely pathogenic
3065463	NM_004371.4(COPA):c.1742T>A (p.Leu581Gln)	Likely pathogenic

SpliceAI

4187 predictions. Top by Δscore:

Variant	Effect	Δscore
1:160290486:ACTT:A	donor_loss	1.0000
1:160290487:CT:C	donor_loss	1.0000
1:160290487:CTTA:C	donor_gain	1.0000
1:160290488:TT:T	donor_loss	1.0000
1:160290489:TACTG:T	donor_loss	1.0000
1:160290490:A:AC	donor_gain	1.0000
1:160290491:C:CT	donor_gain	1.0000
1:160290491:CT:C	donor_gain	1.0000
1:160290491:CTG:C	donor_gain	1.0000
1:160290491:CTGT:C	donor_gain	1.0000
1:160290556:TTTTC:T	donor_gain	1.0000
1:160290557:TTTCT:T	donor_gain	1.0000
1:160290682:CGGGT:C	acceptor_gain	1.0000
1:160290683:GGGT:G	acceptor_gain	1.0000
1:160290684:GGT:G	acceptor_gain	1.0000
1:160290685:GT:G	acceptor_gain	1.0000
1:160290685:GTCT:G	acceptor_loss	1.0000
1:160290687:C:CC	acceptor_gain	1.0000
1:160291305:C:A	donor_gain	1.0000
1:160291330:TCTA:T	donor_loss	1.0000
1:160291332:TA:T	donor_loss	1.0000
1:160291333:AC:A	donor_loss	1.0000
1:160291334:C:CA	donor_loss	1.0000
1:160291493:CCAT:C	acceptor_gain	1.0000
1:160291494:CAT:C	acceptor_gain	1.0000
1:160291494:CATC:C	acceptor_gain	1.0000
1:160291496:TC:T	acceptor_loss	1.0000
1:160291497:C:CC	acceptor_gain	1.0000
1:160291497:CTG:C	acceptor_loss	1.0000
1:160291506:A:T	acceptor_gain	1.0000

AlphaMissense

8049 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:160295788:C:A	W808C	1.000
1:160295788:C:G	W808C	1.000
1:160295790:A:G	W808R	1.000
1:160295790:A:T	W808R	1.000
1:160296129:C:G	A762P	1.000
1:160296140:G:T	A758D	1.000
1:160297360:A:G	L749P	1.000
1:160297556:C:G	A723P	1.000
1:160297558:A:C	I722S	1.000
1:160297558:A:G	I722T	1.000
1:160297558:A:T	I722N	1.000
1:160297567:A:C	M719R	1.000
1:160297576:A:G	L716P	1.000
1:160297591:C:A	G711V	1.000
1:160297591:C:T	G711D	1.000
1:160297615:A:G	L703P	1.000
1:160297615:A:T	L703H	1.000
1:160297636:C:G	R696P	1.000
1:160297638:C:A	Q695H	1.000
1:160297638:C:G	Q695H	1.000
1:160297669:C:A	G685V	1.000
1:160297669:C:T	G685E	1.000
1:160297670:C:A	G685W	1.000
1:160297670:C:G	G685R	1.000
1:160297670:C:T	G685R	1.000
1:160297681:G:T	A681D	1.000
1:160297693:A:G	L677P	1.000
1:160297703:A:G	W674R	1.000
1:160297703:A:T	W674R	1.000
1:160297729:G:T	A665D	1.000

dbSNP variants (sampled 300 via entrez): RS1000014849 (1:160300768 G>A,C), RS1000048931 (1:160300532 T>A), RS1000108292 (1:160292327 AG>A), RS1000150863 (1:160304060 G>A), RS1000205815 (1:160339219 T>A), RS1000387807 (1:160336439 T>A,C), RS1000426487 (1:160289478 A>C), RS1000449872 (1:160345014 C>G,T), RS1000476484 (1:160307779 C>G,T), RS1000497272 (1:160290994 C>A), RS1000506041 (1:160306285 G>A), RS1000586547 (1:160344476 T>G), RS1000625784 (1:160337716 C>A,T), RS1000651108 (1:160299125 G>A), RS1000700868 (1:160331582 G>C)

Disease associations

OMIM: gene MIM:601924 | disease phenotypes: MIM:616414, MIM:104200, MIM:601744

GenCC curated gene-disease

Disease	Classification	Inheritance
autoimmune interstitial lung disease-arthritis syndrome	Strong	Autosomal dominant

Mondo (4): autoimmune interstitial lung disease-arthritis syndrome (MONDO:0014629), autosomal dominant Alport syndrome (MONDO:0007086), systemic lupus erythematosus, susceptibility to, 1 (MONDO:0011138), autoinflammation and autoimmunity with immune dysregulation 1 (MONDO:0700391)

Orphanet (3): Autoimmune interstitial lung disease-arthritis syndrome (Orphanet:444092), Alport syndrome (Orphanet:63), Autosomal dominant Alport syndrome (Orphanet:88918)

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001369	Arthritis
HP:0002091	Restrictive ventilatory defect
HP:0002094	Dyspnea
HP:0002789	Tachypnea
HP:0002829	Arthralgia
HP:0003493	Antinuclear antibody positivity
HP:0003565	Elevated erythrocyte sedimentation rate
HP:0006530	Abnormal pulmonary interstitial morphology
HP:0008653	Crescentic glomerulonephritis
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0011463	Childhood onset
HP:0012574	Mesangial hypercellularity
HP:0012735	Cough
HP:0032979	Hemosiderin-laden macrophages in bronchoalveolar fluid
HP:0040223	Pulmonary hemorrhage
HP:0045051	Decreased DLCO

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003985_16	Breast size	1.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066870 (SINGLE PROTEIN)

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

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	127.2	nM	CHEMBL3752910
6.90	ED50	127.2	nM	CHEMBL3752910
6.19	Kd	652	nM	CHEMBL5653589
6.19	ED50	652	nM	CHEMBL5653589

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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148114: Binding affinity to human COPA incubated for 45 mins by Kinobead based pull down assay	kd	0.1272	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148114: Binding affinity to human COPA incubated for 45 mins by Kinobead based pull down assay	kd	0.6520	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases methylation	3
Tobacco Smoke Pollution	affects expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Lead	decreases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
methylmercuric chloride	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects localization, increases expression, affects cotreatment	1
arsenite	increases methylation	1
methylparaben	increases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
ciglitazone	affects binding, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
chloropicrin	increases expression	1
U 0126	affects expression, affects reaction	1
K 7174	increases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Irinotecan	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Atrazine	decreases 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
CHEMBL5651156	Binding	Binding affinity to human COPA 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)

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