COPG1

Summary

COPG1 (coat protein complex I subunit gamma 1, HGNC:2236) is a protein-coding gene on chromosome 3q21.3, encoding Coatomer subunit gamma-1 (Q9Y678). 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 90.8% of cancer cell lines).

Predicted to enable structural molecule activity. Predicted to be involved in several processes, including Golgi vesicle transport; establishment of Golgi localization; and organelle transport along microtubule. Located in Golgi apparatus. Implicated in immunodeficiency 128.

Source: NCBI Gene 22820 — RefSeq curated summary.

At a glance

• Gene–disease (curated): non-severe combined immunodeficiency due to COPG1 deficiency (Limited, ClinGen)
• GWAS associations: 9
• Clinical variants (ClinVar): 175 total — 1 pathogenic
• Phenotypes (HPO): 12
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 90.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_016128

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2236
Approved symbol	COPG1
Name	coat protein complex I subunit gamma 1
Location	3q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000181789
Ensembl biotype	protein_coding
OMIM	615525
Entrez	22820

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 21 protein_coding, 6 retained_intron, 2 nonsense_mediated_decay

ENST00000314797, ENST00000504350, ENST00000504547, ENST00000509208, ENST00000509889, ENST00000512034, ENST00000513410, ENST00000513965, ENST00000514478, ENST00000515725, ENST00000865880, ENST00000865881, ENST00000865882, ENST00000865883, ENST00000865884, ENST00000865885, ENST00000911368, ENST00000911369, ENST00000911370, ENST00000911371, ENST00000961555, ENST00000961556, ENST00000961557, ENST00000961558, ENST00000961559, ENST00000961560, ENST00000961561, ENST00000961562, ENST00000961563

RefSeq mRNA: 1 — MANE Select: NM_016128 NM_016128

CCDS: CCDS33851

Canonical transcript exons

ENST00000314797 — 24 exons

Exon	Start	End
ENSE00002082831	129249606	129249746
ENSE00003458548	129272244	129272415
ENSE00003460276	129254668	129254743
ENSE00003460535	129252281	129252361
ENSE00003461736	129257727	129257860
ENSE00003489437	129256068	129256154
ENSE00003493269	129252623	129252694
ENSE00003497890	129250682	129250734
ENSE00003509031	129272807	129272904
ENSE00003509174	129271767	129271909
ENSE00003511674	129254985	129255077
ENSE00003512261	129252876	129252955
ENSE00003520274	129275194	129275292
ENSE00003520845	129260333	129260400
ENSE00003543979	129257470	129257627
ENSE00003559596	129265549	129265792
ENSE00003563455	129267024	129267099
ENSE00003581105	129274838	129274976
ENSE00003594870	129268495	129268620
ENSE00003614042	129277294	129277773
ENSE00003618446	129268932	129269000
ENSE00003632760	129267937	129268040
ENSE00003634283	129260619	129260807
ENSE00003662448	129263904	129263999

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 99.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 75.3339 / max 291.0547, expressed in 1826 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38513	75.3339	1826

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.00	gold quality
adenohypophysis	UBERON:0002196	98.88	gold quality
body of pancreas	UBERON:0001150	98.76	gold quality
mucosa of transverse colon	UBERON:0004991	98.64	gold quality
pituitary gland	UBERON:0000007	98.44	gold quality
islet of Langerhans	UBERON:0000006	98.26	gold quality
minor salivary gland	UBERON:0001830	98.20	gold quality
right lobe of thyroid gland	UBERON:0001119	98.10	gold quality
body of stomach	UBERON:0001161	98.01	gold quality
right adrenal gland	UBERON:0001233	97.97	gold quality
rectum	UBERON:0001052	97.96	gold quality
left lobe of thyroid gland	UBERON:0001120	97.93	gold quality
left adrenal gland	UBERON:0001234	97.92	gold quality
endocervix	UBERON:0000458	97.88	gold quality
upper lobe of left lung	UBERON:0008952	97.88	gold quality
left adrenal gland cortex	UBERON:0035825	97.82	gold quality
right adrenal gland cortex	UBERON:0035827	97.81	gold quality
transverse colon	UBERON:0001157	97.75	gold quality
ascending aorta	UBERON:0001496	97.75	gold quality
thoracic aorta	UBERON:0001515	97.73	gold quality
calcaneal tendon	UBERON:0003701	97.70	gold quality
right ovary	UBERON:0002118	97.65	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.61	gold quality
metanephros cortex	UBERON:0010533	97.61	gold quality
adrenal cortex	UBERON:0001235	97.55	gold quality
saliva-secreting gland	UBERON:0001044	97.52	gold quality
ectocervix	UBERON:0012249	97.49	gold quality
right lobe of liver	UBERON:0001114	97.48	gold quality
adrenal gland	UBERON:0002369	97.47	gold quality
body of uterus	UBERON:0009853	97.41	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.20
E-MTAB-7303	no	453.09
E-MTAB-6058	no	198.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting COPG1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-145-3P	99.33	67.66	764
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-7151-3P	99.04	69.72	2370

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 90.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 6)

• The D1 receptor associates with the gamma-subunit of the COPI coatomer complex. Association between the coatomer complex and hydrophobic residues within the proximal C-terminus of the D1 receptor may serve an important role in receptor transport. (PMID:11893085)
• Results describe the structure of the appendage domain of gamma-COP and show that it has a similar overall fold as the alpha-appendage of AP2. (PMID:14690497)
• ERManI and gamma-COP contribute to a golgi-based quality control module that facilitates the retrieval of captured ERAD substrates back to the endoplasmic reticulum. (PMID:23427261)
• These data unveil the molecular mechanism of Golgi retention of kAE1 G701D and suggest that disruption of the COPI-kAE1 G701D interaction could be a therapeutic strategy to treat distal renal tubular acidosis caused by this mutant. (PMID:28646128)
• The bacterial copper resistance protein CopG contains a cysteine-bridged tetranuclear copper cluster. (PMID:32571874)
• Combined immunodeficiency due to a mutation in the gamma1 subunit of the coat protein I complex. (PMID:33529166)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Copg1	ENSMUSG00000030058
rattus_norvegicus	Copg1	ENSRNOG00000010474
drosophila_melanogaster	gammaCOP	FBGN0028968
caenorhabditis_elegans		WBGENE00011775

Paralogs (1): COPG2 (ENSG00000158623)

Protein

Protein identifiers

Coatomer subunit gamma-1 — Q9Y678 (reviewed: Q9Y678)

Alternative names: Gamma-1-coat protein

All UniProt accessions (4): D6RG17, Q9Y678, H0Y8G2, H0Y8X7

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. 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 triglyceride lipase (PNPLA2) with the lipid droplet surface to mediate lipolysis.

Subunit / interactions. Oligomeric complex that consists of at least the alpha, beta, beta’, gamma, delta, epsilon and zeta subunits. Interacts with ZNF289/ARFGAP2 through its C-terminal appendage domain. Interacts with EGFR upon EGF treatment; interaction is essential for regulation of EGF-dependent nuclear transport of EGFR by retrograde trafficking from the Golgi to the ER. The coatomer interacts with KDEL receptors; the interaction is important for retrograde trafficking of KDEL-bearing proteins from the Golgi to the endoplasmic reticulum. Interacts with COPB1. Interacts with TMED10 (via C-terminus). Interacts with TMED2, TMED3, TMED7 and TMED9.

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

Disease relevance. Immunodeficiency 128 (IMD128) [MIM:620983] An autosomal recessive immunologic disorder characterized by persistent bacterial and viral infections manifesting in the first year of life, and defective humoral and cellular immunity. Affected individuals suffer from recurrent respiratory infections, bronchiectasis, and failure to thrive. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the COPG family.

RefSeq proteins (1): NP_057212* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002553	Clathrin/coatomer_adapt-like_N	Domain
IPR009028	Coatomer/calthrin_app_sub_C	Homologous_superfamily
IPR011989	ARM-like	Homologous_superfamily
IPR012295	TBP_dom_sf	Homologous_superfamily
IPR013040	Coatomer_gsu_app_Ig-like_dom	Domain
IPR013041	Clathrin_app_Ig-like_sf	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR017106	Coatomer_gsu	Family
IPR032154	Coatomer_g_Cpla	Domain
IPR037067	Coatomer_gsu_app_sf	Homologous_superfamily

Pfam: PF01602, PF08752, PF16381

UniProt features (39 total): strand 14, helix 6, repeat 4, sequence conflict 4, turn 3, sequence variant 2, region of interest 2, chain 1, mutagenesis site 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1R4X	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y678-F1	88.09	0.61

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 (1): 594

Mutagenesis-validated functional residues (1):

Position	Phenotype
776	loss of interaction with znf289/arfgap2.

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: 169 (showing top): TGCGCANK_UNKNOWN, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, GOBP_INTRA_GOLGI_VESICLE_MEDIATED_TRANSPORT, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, GOCC_COATED_VESICLE, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_SECRETION, GOCC_GOLGI_ASSOCIATED_VESICLE, GOCC_VESICLE_COAT, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, chr3q21, GOBP_GOLGI_LOCALIZATION

GO Biological Process (8): intracellular protein transport (GO:0006886), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), intra-Golgi vesicle-mediated transport (GO:0006891), protein secretion (GO:0009306), establishment of Golgi localization (GO:0051683), organelle transport along microtubule (GO:0072384), 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 (16): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), Golgi apparatus (GO:0005794), cytosol (GO:0005829), COPI vesicle coat (GO:0030126), transport vesicle (GO:0030133), cytoplasm (GO:0005737), endomembrane system (GO:0012505), membrane (GO:0016020), membrane coat (GO:0030117), COPI-coated vesicle membrane (GO:0030663), organelle membrane (GO:0031090), cytoplasmic vesicle (GO:0031410), intracellular vesicle (GO:0097708)

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	7
intracellular membrane-bounded organelle	4
cellular anatomical structure	4
endomembrane system	3
intracellular protein localization	2
protein transport	2
intracellular transport	2
Golgi vesicle transport	2
establishment of organelle localization	2
transport	2
Golgi apparatus	2
intracellular anatomical structure	2
intercellular transport	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
Golgi localization	1
establishment of localization in cell	1
transport along microtubule	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
vesicle coat	1
COPI-coated vesicle membrane	1
cytoplasmic vesicle	1
vacuole	1
plasma membrane	1
coated membrane	1
membrane protein complex	1
COPI-coated vesicle	1
Golgi-associated vesicle membrane	1
coated vesicle membrane	1
membrane	1
membrane-bounded organelle	1
intracellular vesicle	1

Protein interactions and networks

STRING

1654 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COPG1	COPB1	P53618	993
COPG1	COPB2	P35606	993
COPG1	ARCN1	P48444	984
COPG1	COPZ1	P61923	898
COPG1	COPE	O14579	772
COPG1	COPA	P53621	761
COPG1	COPZ2	Q9P299	750
COPG1	TMED10	P49755	541
COPG1	PRPF8	Q6P2Q9	531
COPG1	COPG2	Q9UBF2	517
COPG1	SEC13	P55735	475
COPG1	RPL5	P46777	450
COPG1	SEC31A	O94979	444
COPG1	XPOT	O43592	443
COPG1	RPS9	P46781	432

IntAct

175 interactions, top by confidence:

A	B	Type	Score
CFTR	COPG1	psi-mi:“MI:0915”(physical association)	0.790
COPG1	COPB1	psi-mi:“MI:0914”(association)	0.730
COPG1	COPB2	psi-mi:“MI:0914”(association)	0.730
SUN2	LMNA	psi-mi:“MI:0914”(association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
COPG1	NUDCD1	psi-mi:“MI:0915”(physical association)	0.710
SACM1L	COPG1	psi-mi:“MI:0915”(physical association)	0.680
COPG1	SACM1L	psi-mi:“MI:0915”(physical association)	0.680
COPB1	COPZ1	psi-mi:“MI:0914”(association)	0.640
COPG1	COPE	psi-mi:“MI:0914”(association)	0.640
SACM1L	COPE	psi-mi:“MI:0914”(association)	0.640
Copa	COPE	psi-mi:“MI:0915”(physical association)	0.560
CCDC107	PLD2	psi-mi:“MI:0914”(association)	0.530
PRKCSH	AURKA	psi-mi:“MI:0914”(association)	0.530
TMED9	COPB2	psi-mi:“MI:0914”(association)	0.530
CD74	PGRMC1	psi-mi:“MI:0914”(association)	0.530

BioGRID (387): COPG1 (Affinity Capture-MS), COPG1 (Affinity Capture-MS), COPG1 (Affinity Capture-MS), COPG1 (Affinity Capture-MS), COPG1 (Affinity Capture-MS), COPG1 (Affinity Capture-MS), COPA (Co-fractionation), COPB1 (Co-fractionation), COPG1 (Co-fractionation), COPG1 (Co-fractionation), COPG1 (Co-fractionation), COPG1 (Co-fractionation), COPG1 (Co-fractionation), COPG1 (Co-fractionation), COPG1 (Co-fractionation)

ESM2 similar proteins: A1A5G0, A1A5K2, A2AGT5, A2VE21, A7MBJ5, D4ABY2, G5EEM5, O35643, O81742, P22892, P52303, P53620, P55060, P62944, P63009, P63010, P97536, Q08DS7, Q0WW26, Q10567, Q14008, Q1ZXQ8, Q29AE5, Q32PG1, Q4AEF8, Q4U0G1, Q5N749, Q5R6L5, Q5RHR0, Q66JI9, Q6DDM4, Q6DKD7, Q6GM65, Q6Z382, Q6ZQ38, Q7Z460, Q80TV8, Q86VP6, Q8H852, Q94FN2

Diamond homologs: A2VE21, D4ABY2, P32074, P53620, P87140, Q0WW26, Q22498, Q29AE5, Q4AEF8, Q54HL0, Q66JI9, Q6DKD7, Q6Z382, Q7PVF6, Q8H852, Q8I0G5, Q9I8E6, Q9PUE4, Q9QXK3, Q9QZE5, Q9UBF2, Q9Y678

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 169 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	12.3×	2e-08
COPI-mediated anterograde transport	12	11.3×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	11	25.4×	5e-10
intra-Golgi vesicle-mediated transport	7	25.2×	4e-06
endoplasmic reticulum to Golgi vesicle-mediated transport	13	12.1×	4e-08
protein import into nucleus	8	7.9×	2e-03
intracellular protein transport	12	5.3×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	118
Likely benign	7
Benign	18

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1183991	Single allele	Pathogenic

SpliceAI

2969 predictions. Top by Δscore:

Variant	Effect	Δscore
3:129249734:GA:G	donor_gain	1.0000
3:129249742:GTCAG:G	donor_gain	1.0000
3:129249743:TCAGG:T	donor_loss	1.0000
3:129249744:CAGGT:C	donor_loss	1.0000
3:129249745:AGGTG:A	donor_loss	1.0000
3:129249746:GGTGA:G	donor_loss	1.0000
3:129249747:G:C	donor_loss	1.0000
3:129249748:T:A	donor_loss	1.0000
3:129252275:TCTTA:T	acceptor_loss	1.0000
3:129252276:CTTA:C	acceptor_loss	1.0000
3:129252277:TTA:T	acceptor_loss	1.0000
3:129252278:TAGG:T	acceptor_loss	1.0000
3:129252279:A:AG	acceptor_gain	1.0000
3:129252280:G:GG	acceptor_gain	1.0000
3:129252280:G:GT	acceptor_loss	1.0000
3:129252280:GGCCC:G	acceptor_gain	1.0000
3:129252611:T:TA	acceptor_gain	1.0000
3:129252616:A:AG	acceptor_gain	1.0000
3:129252618:C:G	acceptor_gain	1.0000
3:129252619:A:AG	acceptor_gain	1.0000
3:129252619:ACAG:A	acceptor_gain	1.0000
3:129252619:ACAGG:A	acceptor_gain	1.0000
3:129252620:C:G	acceptor_gain	1.0000
3:129252620:CAGG:C	acceptor_loss	1.0000
3:129252621:A:AG	acceptor_gain	1.0000
3:129252621:A:G	acceptor_loss	1.0000
3:129252621:AG:A	acceptor_gain	1.0000
3:129252621:AGG:A	acceptor_gain	1.0000
3:129252621:AGGG:A	acceptor_gain	1.0000
3:129252621:AGGGG:A	acceptor_gain	1.0000

AlphaMissense

5775 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:129252281:G:C	A31P	1.000
3:129252662:T:C	F71L	1.000
3:129252664:T:A	F71L	1.000
3:129252664:T:G	F71L	1.000
3:129252678:T:C	L76P	1.000
3:129252885:C:A	R85S	1.000
3:129252943:T:A	I104N	1.000
3:129252946:T:A	V105D	1.000
3:129252951:A:C	S107R	1.000
3:129252953:C:A	S107R	1.000
3:129252953:C:G	S107R	1.000
3:129254670:T:A	L109Q	1.000
3:129254670:T:C	L109P	1.000
3:129254715:C:A	A124D	1.000
3:129254723:G:C	A127P	1.000
3:129254727:T:C	L128P	1.000
3:129255009:C:A	R142S	1.000
3:129255018:A:G	K145E	1.000
3:129255024:G:C	A147P	1.000
3:129255061:C:A	A159D	1.000
3:129256104:T:A	W177R	1.000
3:129256104:T:C	W177R	1.000
3:129256125:G:C	A184P	1.000
3:129257476:G:C	A196P	1.000
3:129257477:C:A	A196E	1.000
3:129257519:C:A	A210D	1.000
3:129257591:G:C	R234P	1.000
3:129257797:G:C	A270P	1.000
3:129257798:C:A	A270D	1.000
3:129257800:G:C	A271P	1.000

dbSNP variants (sampled 300 via entrez): RS1000047713 (3:129252550 T>G), RS1000123664 (3:129258201 G>A), RS1000190328 (3:129274666 C>T), RS1000268539 (3:129270084 A>G), RS1000410544 (3:129258449 G>A), RS1000521405 (3:129276381 C>G), RS1000828628 (3:129258934 A>C), RS1000896910 (3:129264070 G>A,C), RS1000966859 (3:129263809 C>A,G,T), RS1001045188 (3:129269624 G>A), RS1001054233 (3:129276726 T>C), RS1001301649 (3:129278145 T>C), RS1001347340 (3:129270678 T>C), RS1001688088 (3:129259861 G>A), RS1001758815 (3:129271020 C>T)

Disease associations

OMIM: gene MIM:615525 | disease phenotypes: MIM:614038, MIM:620983

GenCC curated gene-disease

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
non-severe combined immunodeficiency due to COPG1 deficiency	Limited	AR

Mondo (3): deafness-lymphedema-leukemia syndrome (MONDO:0013540), GATA2 deficiency with susceptibility to MDS/AML (MONDO:0042982), immunodeficiency 128 (MONDO:0975834)

Orphanet (1): Deafness-lymphedema-leukemia syndrome (Orphanet:3226)

HPO phenotypes

12 total (12 of 12 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003593	Infantile onset
HP:0005403	Decreased total T cell count
HP:0005415	Decreased CD8+ T cell proportion
HP:0010976	Decreased total B cell count
HP:0025834	Decreased PHA-induced T-cell proliferation
HP:0031382	Decreased anti-CD3/28-induced T-cell proliferation
HP:0031396	Abnormal naive T cell proportion
HP:0032182	Abnormal memory T cell proportion
HP:0032218	Decreased CD4+ T cell proportion
HP:0040218	Reduced total natural killer cell count
HP:0500269	Abnormal gamma-delta T cell proportion

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST005956_82	Waist-to-hip ratio adjusted for BMI	2.000000e-07
GCST005958_5	Waist-to-hip ratio adjusted for BMI (age >50)	4.000000e-10
GCST005962_16	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-11
GCST008839_445	Height	7.000000e-23
GCST90020025_587	Waist-to-hip ratio adjusted for BMI	3.000000e-11
GCST90020026_222	Hip index	3.000000e-09
GCST90020027_364	Waist-hip index	1.000000e-10
GCST90020028_1835	Hip circumference adjusted for BMI	7.000000e-15
GCST90020028_1837	Hip circumference adjusted for BMI	1.000000e-21

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724764 (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
6.78	Kd	164.3	nM	CHEMBL3752910
6.78	ED50	164.3	nM	CHEMBL3752910
6.01	IC50	980	nM	MOLIBRESIB
5.56	Kd	2745	nM	CHEMBL5653589
5.56	ED50	2745	nM	CHEMBL5653589

PubChem BioAssay actives

3 with measured affinity, of 10 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148118: Binding affinity to human COPG1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1643	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179052: Inhibition of COPG (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.9800	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148118: Binding affinity to human COPG1 incubated for 45 mins by Kinobead based pull down assay	kd	2.7453	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	3
bisphenol A	affects expression, increases expression	2
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Tunicamycin	increases expression	2
Thapsigargin	increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment, decreases expression	1
beta-lapachone	decreases expression, increases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	decreases methylation	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	increases expression, increases secretion, affects cotreatment	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Caffeine	decreases phosphorylation	1
Dactinomycin	affects cotreatment, increases expression, increases secretion	1
Dexamethasone	affects cotreatment, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Furaldehyde	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Methapyrilene	decreases methylation	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651160	Binding	Binding affinity to human COPG1 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)

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

Trial	Phase	Status	Title
NCT04844177	PHASE2	UNKNOWN	Total Lymphoid Irradiation Pre-HSCT in Severe Congenital Neutropenia
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT01905826	Not specified	RECRUITING	Natural History Study of GATA2 Deficiency and Related Disorders