COG2

Summary

COG2 (component of oligomeric golgi complex 2, HGNC:6546) is a protein-coding gene on chromosome 1q42.2, encoding Conserved oligomeric Golgi complex subunit 2 (Q14746). Required for normal Golgi morphology and function. It is a selective cancer dependency (DepMap: 61.3% of cell lines).

This gene encodes a subunit of the conserved oligomeric Golgi complex that is required for maintaining normal structure and activity of the Golgi complex. The encoded protein specifically interacts with the USO1 vesicle docking protein and may be necessary for normal Golgi ribbon formation and trafficking of Golgi enzymes. Mutations of this gene are associated with abnormal glycosylation within the Golgi apparatus. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 22796 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital disorder of glycosylation, type IIq (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 309 total — 6 pathogenic, 3 likely-pathogenic (top 10% of genes corpus-wide)
• GTEx eGene: eQTL in 20 tissues, sQTL in 23 (q < 0.05)
• Phenotypes (HPO): 19
• Cancer dependency (DepMap): dependent in 61.3% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.72 (unconstrained)
• MANE Select transcript: NM_007357

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6546
Approved symbol	COG2
Name	component of oligomeric golgi complex 2
Location	1q42.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000135775
Ensembl biotype	protein_coding
OMIM	606974
Entrez	22796

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 14 protein_coding, 12 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 2 retained_intron

MANE Select: ENST00000366669

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 6, TSL 3: 1

ENST00000366669, ENST00000366668, ENST00000468893, ENST00000473671, ENST00000478710, ENST00000482012, ENST00000490900, ENST00000494371, ENST00000534989, ENST00000865123, ENST00000865124, ENST00000921491, ENST00000964684, ENST00000964685, ENST00000964686, ENST00000964687, ENST00000964688, ENST00000964689, ENST00001005045, ENST00001005046, ENST00001005047, ENST00001055550, ENST00001055552, ENST00001055553, ENST00001055554, ENST00001055555, ENST00001055556, ENST00001055557, ENST00001059137, ENST00001123667, ENST00001145526

RefSeq mRNA: 2 — MANE Select: NM_007357 NM_001145036, NM_007357

CCDS: CCDS1584, CCDS44329

Canonical transcript exons

ENST00000366669 — 18 exons

Exon	Start	End
ENSE00000805217	230671516	230671640
ENSE00000805220	230683574	230683635
ENSE00000805224	230688420	230688562
ENSE00000805225	230690014	230690153
ENSE00000805226	230691384	230691564
ENSE00001262174	230678913	230679052
ENSE00001714340	230693292	230693982
ENSE00001919434	230642481	230642678
ENSE00003489447	230685085	230685236
ENSE00003504093	230688071	230688143
ENSE00003505850	230669356	230669535
ENSE00003576229	230686935	230687132
ENSE00003601809	230660758	230660823
ENSE00003616218	230668676	230668784
ENSE00003621610	230664484	230664587
ENSE00003623857	230663141	230663221
ENSE00003628018	230674998	230675124
ENSE00003673231	230659464	230659625

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 91.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.2562 / max 136.6362, expressed in 1813 samples.

Highest expression (Bgee): rectum, hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex, adrenal gland cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

COG2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 20 tissues and its splicing (sQTL) in 23 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 43 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	sqtl	8.9e-41	-0.77	1:230683095:G:T
Thyroid	sqtl	6.6e-26	-0.63	1:230683095:G:T
Skin Not Sun Exposed Suprapubic	sqtl	1.4e-16	-0.56	1:230690196:A:G
Nerve Tibial	sqtl	1.5e-16	-0.60	1:230684605:A:G
Artery Coronary	eqtl	2.9e-16	+3.88	1:231547989:C:T
Adipose Subcutaneous	sqtl	5.6e-12	-0.45	1:230683095:G:T
Breast Mammary Tissue	sqtl	6.9e-11	-0.53	1:230683095:G:T
Esophagus Mucosa	eqtl	2.1e-08	+0.14	1:230642745:G:C
Heart Atrial Appendage	sqtl	3.9e-08	-0.49	1:230680438:T:G
Brain Cerebellum	eqtl	4.1e-08	+1.81	1:231172647:C:T
Colon Transverse	sqtl	1.7e-07	-0.45	1:230680473:G:A
Esophagus Gastroesophageal Junction	sqtl	2.3e-07	-0.46	1:230684275:A:G
Thyroid	eqtl	1.6e-06	+0.45	1:230668288:T:A
Esophagus Mucosa	sqtl	3.2e-06	-0.36	1:230690196:A:G
Artery Tibial	sqtl	3.2e-06	-0.37	1:230683095:G:T
Lung	sqtl	4.9e-06	-0.37	1:230680438:T:G
Brain Cerebellum	sqtl	1.1e-05	-0.67	1:230693241:C:A
Brain Cerebellar Hemisphere	eqtl	1.6e-05	+0.71	1:231527853:T:C
Prostate	sqtl	3.8e-05	-0.59	1:230680438:T:G
Cells Cultured fibroblasts	sqtl	4.6e-05	-0.35	1:230684605:A:G

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
9033	16.6052	1813
9034	0.6510	381

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	91.62	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.22	gold quality
cerebellar hemisphere	UBERON:0002245	91.10	gold quality
cerebellar cortex	UBERON:0002129	90.98	gold quality
right adrenal gland cortex	UBERON:0035827	90.92	gold quality
right adrenal gland	UBERON:0001233	90.74	gold quality
pancreatic ductal cell	CL:0002079	90.09	gold quality
islet of Langerhans	UBERON:0000006	90.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.85	gold quality
left adrenal gland	UBERON:0001234	89.84	gold quality
adrenal tissue	UBERON:0018303	89.79	gold quality
cerebellum	UBERON:0002037	89.48	gold quality
left adrenal gland cortex	UBERON:0035825	89.48	gold quality
adrenal gland	UBERON:0002369	89.00	gold quality
granulocyte	CL:0000094	88.59	gold quality
adrenal cortex	UBERON:0001235	88.43	gold quality
tibialis anterior	UBERON:0001385	88.41	gold quality
monocyte	CL:0000576	88.33	gold quality
mononuclear cell	CL:0000842	88.19	gold quality
leukocyte	CL:0000738	88.15	gold quality
apex of heart	UBERON:0002098	88.04	gold quality
transverse colon	UBERON:0001157	87.88	gold quality
calcaneal tendon	UBERON:0003701	87.85	gold quality
ileal mucosa	UBERON:0000331	87.61	gold quality
gastrocnemius	UBERON:0001388	87.52	gold quality
muscle of leg	UBERON:0001383	87.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.45	gold quality
pancreas	UBERON:0001264	87.42	gold quality
right atrium auricular region	UBERON:0006631	87.29	gold quality
body of pancreas	UBERON:0001150	87.28	gold quality
right uterine tube	UBERON:0001302	87.17	gold quality
mucosa of transverse colon	UBERON:0004991	87.11	gold quality
metanephros cortex	UBERON:0010533	86.65	gold quality
body of stomach	UBERON:0001161	86.57	gold quality
cardiac atrium	UBERON:0002081	86.55	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.45	gold quality
right lobe of thyroid gland	UBERON:0001119	86.42	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.25	gold quality
sural nerve	UBERON:0015488	85.91	gold quality
large intestine	UBERON:0000059	85.85	gold quality
minor salivary gland	UBERON:0001830	85.85	gold quality
colon	UBERON:0001155	85.80	gold quality
intestine	UBERON:0000160	85.67	gold quality
spleen	UBERON:0002106	85.61	gold quality
heart left ventricle	UBERON:0002084	85.57	gold quality
mucosa of sigmoid colon	UBERON:0004993	85.56	gold quality
heart	UBERON:0000948	85.41	gold quality
left lobe of thyroid gland	UBERON:0001120	85.40	gold quality
endocervix	UBERON:0000458	85.37	gold quality
cardiac ventricle	UBERON:0002082	85.30	gold quality
gall bladder	UBERON:0002110	85.20	gold quality
small intestine	UBERON:0002108	85.09	gold quality
tibial nerve	UBERON:0001323	85.02	gold quality
skin of leg	UBERON:0001511	85.02	gold quality
saliva-secreting gland	UBERON:0001044	84.98	gold quality
popliteal artery	UBERON:0002250	84.96	gold quality
tibial artery	UBERON:0007610	84.95	gold quality
muscle organ	UBERON:0001630	84.93	gold quality
stomach	UBERON:0000945	84.91	gold quality
colonic mucosa	UBERON:0000317	84.90	gold quality
sigmoid colon	UBERON:0001159	84.88	gold quality
skin of abdomen	UBERON:0001416	84.86	gold quality
parotid gland	UBERON:0001831	84.85	gold quality
left coronary artery	UBERON:0001626	84.82	gold quality
thyroid gland	UBERON:0002046	84.75	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.73	gold quality
body of uterus	UBERON:0009853	84.50	gold quality
ectocervix	UBERON:0012249	84.50	gold quality
aorta	UBERON:0000947	84.48	gold quality
right ovary	UBERON:0002118	84.48	gold quality
right coronary artery	UBERON:0001625	84.47	gold quality
lymph node	UBERON:0000029	84.41	gold quality
ventricular zone	UBERON:0003053	84.39	gold quality
descending thoracic aorta	UBERON:0002345	84.27	gold quality
deltoid	UBERON:0001476	84.18	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.08	gold quality
thoracic aorta	UBERON:0001515	84.07	gold quality
mouth mucosa	UBERON:0003729	84.04	gold quality
ascending aorta	UBERON:0001496	84.01	gold quality
left uterine tube	UBERON:0001303	83.95	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.95	gold quality
secondary oocyte	CL:0000655	83.92	gold quality
lower esophagus	UBERON:0013473	83.92	gold quality
right frontal lobe	UBERON:0002810	83.91	gold quality
vermiform appendix	UBERON:0001154	83.86	gold quality
right lobe of liver	UBERON:0001114	83.83	gold quality
upper lobe of left lung	UBERON:0008952	83.73	gold quality
coronary artery	UBERON:0001621	83.69	gold quality
adenohypophysis	UBERON:0002196	83.58	gold quality
zone of skin	UBERON:0000014	83.55	gold quality
endothelial cell	CL:0000115	83.50	gold quality
mucosa of stomach	UBERON:0001199	83.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.26	gold quality
upper lobe of lung	UBERON:0008948	83.26	gold quality
heart right ventricle	UBERON:0002080	83.21	gold quality
right lung	UBERON:0002167	83.13	gold quality
smooth muscle tissue	UBERON:0001135	83.09	gold quality
left ovary	UBERON:0002119	83.09	gold quality
vagina	UBERON:0000996	83.03	gold quality
palpebral conjunctiva	UBERON:0001812	83.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.74

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Parathyroid gland	tissue	66.9
Rectum	tissue	21.3
Periaqueductal gray	tissue	20.6
Thalamus	tissue	20.3
Medulla oblongata	tissue	20.0
Midbrain	tissue	19.7
Spinal cord	tissue	19.7
Tongue	tissue	18.6
Corpus callosum	tissue	18.3
Colon	tissue	17.8
Substantia nigra	tissue	17.8
Superior colliculi	tissue	17.6
Pons	tissue	17.1
Adrenal gland	tissue	16.8
Hippocampal formation	tissue	16.7
Choroid plexus	tissue	16.3
Heart muscle	tissue	16.1
Hypothalamus	tissue	16.1
Skeletal muscle	tissue	15.6
Kidney	tissue	15.5
Thymus	tissue	15.5
Lymph node	tissue	15.2
Tonsil	tissue	15.2
Frontal cortex	tissue	14.9
Septum	tissue	14.6
Amygdala	tissue	14.5
Caudate putamen	tissue	14.5
Thyroid gland	tissue	14.0
Entorhinal cortex	tissue	14.0
Putamen	tissue	13.9
Cerebral cortex	tissue	13.8
Temporal cortex	tissue	13.8
Stomach 1	tissue	13.6
Ventral forebrain	tissue	13.6
Insular cortex	tissue	13.6
Somatosensory cortex	tissue	13.5
Retrosplenial and cingulate cortex	tissue	13.4
Fallopian tube	tissue	13.3
Retrosplenial cortex	tissue	13.3
Cerebellum	tissue	13.2
Occipital cortex	tissue	13.2
Motor cortex	tissue	13.1
Epididymis	tissue	13.0
Basal ganglia	tissue	12.9
Olfactory bulb	tissue	12.8
Prefrontal cortex	tissue	12.7
Duodenum	tissue	12.7
Cervix	tissue	12.3
Pancreas	tissue	12.2
Breast	tissue	12.1
Salivary gland	tissue	12.0
Spleen	tissue	11.9
Small intestine	tissue	11.7
Prostate	tissue	11.4
Smooth muscle	tissue	10.9
Urinary bladder	tissue	10.4
Appendix	tissue	10.4
Gallbladder	tissue	10.3
Testis	tissue	10.2
Seminal vesicle	tissue	10.2

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Dorsal spinal cord (19.7), Ventral spinal cord (19.7), Cerebellar cortex (18.6), White matter (18.3), Flocculonodular lobe (17.5).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting COG2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 36 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-4720-3P	98.50	68.88	988

Functional genomics

gnomAD constraint: pLI 2.3e-06, LOEUF 0.724, missense Z 1.01 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000366669 — one region, missense o/e 0.93. DepMap (CRISPR cell-line fitness): dependent in 61.3% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): TUHR10TKB (-1.653), NCI-H2030 (-1.57), COR-L47 (-1.431), SNB75 (-1.387), JM1 (-1.352), SNU-308 (-1.313), COR-L105 (-1.262), SLR 23 (-1.255), ACC-MESO-1 (-1.251), KASUMI-1 (-1.225), NCI-H647 (-1.187), GAMG (-1.163), COLO-320 (-1.16), MPP 89 (-1.133), SK-LMS-1 (-1.097).

Literature-anchored findings (GeneRIF, showing 2)

• The interaction between p115 and Cog2 was found to be essential for Golgi ribbon reformation after the disruption of the ribbon by p115 KD or brefeldin A treatment and recovery by re-expression of p115 or drug wash out, respectively. (PMID:17274799)
• Our data strongly suggest that these compound heterozygous mutations in COG2 are causative of CDG. (PMID:24784932)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cog2	ENSDARG00000004037
mus_musculus	Cog2	ENSMUSG00000031979
rattus_norvegicus	Cog2	ENSRNOG00000018228
drosophila_melanogaster	Cog2	FBGN0026634
caenorhabditis_elegans		WBGENE00000585

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1923582) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body weight	1
increased circulating triglyceride level	1
increased hematocrit	1
decreased circulating alanine transaminase level	1
decreased circulating creatinine level	1
decreased lactate dehydrogenase level	1
decreased circulating aspartate transaminase level	1
preweaning lethality, complete penetrance	1

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
CAPN9-AS1	ncRNA	107985359
AGT	protein-coding	183
CAPN9	protein-coding	10753
LINC01737	ncRNA	101927553

Protein

Protein identifiers

Conserved oligomeric Golgi complex subunit 2 — Q14746 (reviewed: Q14746)

Alternative names: Component of oligomeric Golgi complex 2, Low density lipoprotein receptor defect C-complementing protein

All UniProt accessions (4): B1ALW7, B7Z2Y2, Q14746, V9GY21

UniProt curated annotations — full annotation on UniProt →

Function. Required for normal Golgi morphology and function.

Subunit / interactions. Component of the conserved oligomeric Golgi complex which is composed of eight different subunits and is required for normal Golgi morphology and localization.

Subcellular location. Golgi apparatus membrane.

Disease relevance. Congenital disorder of glycosylation 2Q (CDG2Q) [MIM:617395] A form of congenital disorder of glycosylation, a genetically heterogeneous group of autosomal recessive, multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. The transmission pattern of CDG2Q is consistent with autosomal recessive inheritance. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the COG2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14746-1	1	yes
Q14746-2	2

RefSeq proteins (2): NP_001138508, NP_031383* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009316	COG2	Family
IPR024602	COG_su2_N	Domain
IPR024603	COG_complex_COG2_C	Domain

Pfam: PF06148, PF12022

UniProt features (9 total): sequence variant 4, region of interest 2, chain 1, compositionally biased region 1, splice variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14746-F1	81.38	0.36

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of glycan/glycoprotein metabolism, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus

Antibody reliability (HPA): IF approved

Function

Pathways and Gene Ontology

Reactome pathways

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

11 pathways:

ID	Pathway	Evidence
R-HSA-6807878	COPI-mediated anterograde transport	curated
R-HSA-6811438	Intra-Golgi traffic	curated
R-HSA-6811440	Retrograde transport at the Trans-Golgi-Network	curated
R-HSA-446203	Asparagine N-linked glycosylation	—
R-HSA-199977	ER to Golgi Anterograde 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: 170 (showing top): GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_INTRA_GOLGI_VESICLE_MEDIATED_TRANSPORT, MODULE_120, GOCC_TRANS_GOLGI_NETWORK, BLALOCK_ALZHEIMERS_DISEASE_UP, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, MODULE_175, YNGTTNNNATT_UNKNOWN, SCHLOSSER_MYC_AND_SERUM_RESPONSE_SYNERGY, GOBP_GOLGI_ORGANIZATION, GOCC_GOLGI_STACK, GOCC_GOLGI_TRANSPORT_COMPLEX, GOCC_TRANS_GOLGI_NETWORK_MEMBRANE

GO Biological Process (4): retrograde transport, vesicle recycling within Golgi (GO:0000301), intra-Golgi vesicle-mediated transport (GO:0006891), Golgi organization (GO:0007030), protein transport (GO:0015031)

GO Molecular Function (2): protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (5): Golgi membrane (GO:0000139), Golgi stack (GO:0005795), COG complex (GO:0017119), trans-Golgi network membrane (GO:0032588), membrane (GO:0016020)

Reactome top-level categories

8 top-level categories:

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

GO top-level categories

15 GO namespaces:

Category	Terms
binding	2
Golgi apparatus	2
intra-Golgi vesicle-mediated transport	1
Golgi vesicle transport	1
organelle organization	1
endomembrane system organization	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
bounding membrane of organelle	1
Golgi apparatus subcompartment	1
vesicle tethering complex	1
trans-Golgi network	1
organelle membrane	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
Golgi organization	BP	mutant phenotype
intra-Golgi vesicle-mediated transport	BP	mutant phenotype
retrograde transport, vesicle recycling within Golgi	BP	mutant phenotype
COG complex	CC	direct assay
Golgi stack	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 910 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COG2	COG1	Q8WTW3	991
COG2	COG3	Q96JB2	985
COG2	COG5	Q9UP83	983
COG2	COG7	P83436	983
COG2	COG8	Q96MW5	964
COG2	COG4	Q9H9E3	958
COG2	COG6	Q9Y2V7	941
COG2	COPB1	P53618	715
COG2	STX5	Q13190	702
COG2	GOSR2	O14653	692
COG2	VPS53	Q5VIR6	640
COG2	TGOLN2	O43493	624
COG2	RIC1	Q4ADV7	605
COG2	STX16	O14662	595
COG2	VPS54	Q9P1Q0	587

IntAct

Human interaction partners of COG2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

11 partners by confidence:

Partner	Interaction type	MIscore	Records
MTUS2	physical association	0.670	5
COG4	physical association	0.670	2
CEP68	physical association	0.560	3
LENG8	physical association	0.560	3
LZTS1	physical association	0.560	3
COG7	association	0.530	1
SPG11	physical association	0.370	1
BSG	association	0.350	1
CST4	association	0.350	1
EEF2K	association	0.350	1
HUNK	physical association	0.000	1

BioGRID (166 interactions; top human partners by supporting records): COG3 (Affinity Capture-MS; 8 records), COG4 (Co-fractionation; 5 records), COG5 (Co-fractionation; 5 records), COG6 (Co-fractionation; 5 records), COG1 (Co-fractionation; 4 records), COG7 (Co-fractionation; 4 records), COG8 (Co-fractionation; 4 records), BSG (Affinity Capture-MS; 3 records), CA14 (Affinity Capture-MS; 3 records), CD274 (Affinity Capture-MS; 3 records), SCN2B (Affinity Capture-MS; 3 records), TEKT4 (Affinity Capture-MS; 3 records), VSIG2 (Affinity Capture-MS; 3 records), ALOX5 (Affinity Capture-MS; 2 records), APLNR (Affinity Capture-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
COG2	“form complex”	“COG tethering complex”	binding

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
COG complex	8	COG2, COG3, COG4, COG5, COG6, COG7, COG8, COG1
COG1-COG8-COG2-COG3-COG4 subcomplex	5	COG1, COG2, COG3, COG4, COG8
COG2-COG3-COG4 subcomplex	3	COG2, COG3, COG4

Disease & clinical

Genetic variants

Variant evidence for COG2: 309 ClinVar records (9 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	3
Uncertain significance	126
Likely benign	94
Benign	50

Top pathogenic / likely-pathogenic (9)

Showing all 9 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
568944	NM_007357.3(COG2):c.436dup (p.Ile146fs)	Pathogenic	criteria provided, single submitter	1
1970272	NM_007357.3(COG2):c.260del (p.Gln87fs)	Pathogenic	criteria provided, single submitter	1
3727680	NM_007357.3(COG2):c.523delinsCAGGCCCATACAGGTGCAATGGTTTTCTGGAGCACCTGTATGCTC (p.Thr175fs)	Pathogenic	criteria provided, single submitter	1
4753913	NM_007357.3(COG2):c.1509del (p.Lys503fs)	Pathogenic	criteria provided, single submitter	1
996958	NM_007357.3(COG2):c.1855C>T (p.Gln619Ter)	Likely pathogenic	criteria provided, single submitter	1
1691000	NM_007357.3(COG2):c.48C>A (p.Cys16Ter)	Likely pathogenic	criteria provided, single submitter	1
4085417	NM_007357.3(COG2):c.1279AGG[1] (p.Arg428del)	Likely pathogenic	criteria provided, single submitter	1
3251550	NC_000001.10:g.(230814799_230819319)_(230820983_230822680)del	Pathogenic	criteria provided, single submitter	1
4689533	NC_000001.10:g.(?230778226)(230829729_?)del	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore COG2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 1,544):

Position(s)	Effect	Δscore	Sites
1:230658862	donor_gain	1.0000
1:230659462–230659463	acceptor_loss	1.0000	4
1:230659626–230659627	donor_loss	1.0000	2
1:230660756–230660757	acceptor_loss	1.0000	6
1:230660824–230660825	donor_loss	1.0000	5
1:230663138–230663139	acceptor_gain	1.0000	2
1:230663139–230663140	acceptor_loss	1.0000	5
1:230663222–230663223	donor_loss	1.0000	4
1:230664477	acceptor_gain	1.0000
1:230664482–230664483	acceptor_loss	1.0000	2

AlphaMissense

1,236 missense substitutions predicted likely pathogenic (of 4,852 scored), across 365 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
F71	8	0.988	1.000
D698	8	0.977	0.986
D67	8	0.970	0.994
F22	8	0.967	0.997
F17	8	0.966	0.996
F27	8	0.961	0.997
F32	8	0.958	0.997
N65	8	0.940	0.995
D687	8	0.930	0.981
S663	8	0.923	0.995
D519	8	0.887	0.950
M660	8	0.866	0.970
D30	8	0.860	0.940
F340	8	0.846	0.958
W380	7	0.967	0.995
R591	7	0.958	0.992
M60	7	0.939	0.992
I64	7	0.922	0.998
Q694	7	0.913	0.985
F182	7	0.891	0.988

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
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	9.1e-05
Glioblastoma Multiforme (TCGA)	favorable	0.000434

Disease associations

OMIM: gene MIM:606974 | disease phenotypes: MIM:617395

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
congenital disorder of glycosylation, type IIq	Strong	Autosomal recessive	2

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
congenital disorder of glycosylation, type IIq	Limited	AR

Mondo (1): congenital disorder of glycosylation, type IIq (MONDO:0054559)

Orphanet (1): COG2-CDG (Orphanet:435934)

HPO phenotypes

19 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001410	Decreased liver function
HP:0001999	Abnormal facial shape
HP:0002079	Hypoplasia of the corpus callosum
HP:0002361	Psychomotor deterioration
HP:0002506	Diffuse cerebral atrophy
HP:0002510	Spastic tetraplegia
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003256	Abnormality of the coagulation cascade
HP:0003593	Infantile onset
HP:0005484	Secondary microcephaly
HP:0010818	Generalized tonic seizure
HP:0010837	Decreased circulating ceruloplasmin concentration
HP:0011967	Decreased circulating copper concentration
HP:0012345	Abnormal glycosylation
HP:0012506	Small pituitary gland

GWAS associations

2 associations:

Study	Trait	p-value
GCST012437_1	Interleukin-6 gene expression levels in non-alcoholic fatty liver disease x mastiha supplementation interaction	1e-8
GCST008359_10	Response to cognitive-behavioural therapy in anxiety disorder	8e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy
EFO:0600067	mastiha supplement exposure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067120 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.46	Kd	3452	nM	CHEMBL3752910
5.46	ED50	3452	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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	2149841: Binding affinity to human COG2 incubated for 45 mins by Kinobead based pull down assay	kd	3.4524	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	increases abundance, increases expression, decreases expression	3
sodium arsenite	decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	affects cotreatment, decreases methylation	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
tetrabromobisphenol A	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Antimycin A	decreases expression	1
Atrazine	decreases expression	1
Cadmium	increases abundance, increases expression	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Dimethyl Sulfoxide	increases expression	1
Ivermectin	decreases expression	1
Lead	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
CHEMBL5652883	Binding	Binding affinity to human COG2 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 COG2 across ~30M SureChEMBL compounds — explore on Sugi Predict.