COG3

Summary

COG3 (component of oligomeric golgi complex 3, HGNC:18619) is a protein-coding gene on chromosome 13q14.13, encoding Conserved oligomeric Golgi complex subunit 3 (Q96JB2). Involved in ER-Golgi transport. It is a selective cancer dependency (DepMap: 89.2% of cell lines).

This gene encodes a component of the conserved oligomeric Golgi (COG) complex which is composed of eight different subunits and is required for normal Golgi morphology and localization. Defects in the COG complex result in multiple deficiencies in protein glycosylation. The protein encoded by this gene is involved in ER-Golgi transport.

Source: NCBI Gene 83548 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital disorder of glycosylation (Limited, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 117 total — 1 pathogenic
• GTEx eGene: eQTL in 27 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 33
• Cancer dependency (DepMap): dependent in 89.2% of screened cell lines
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.31 (highly constrained)
• MANE Select transcript: NM_031431
• Notable: 117 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18619
Approved symbol	COG3
Name	component of oligomeric golgi complex 3
Location	13q14.13
Locus type	gene with protein product
Status	Approved
Aliases	SEC34
Ensembl gene	ENSG00000136152
Ensembl biotype	protein_coding
OMIM	606975
Entrez	83548

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 12 protein_coding, 12 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 1 non_stop_decay

MANE Select: ENST00000349995

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

ENST00000349995, ENST00000465942, ENST00000476702, ENST00000486940, ENST00000617325, ENST00000617493, ENST00000618913, ENST00000904057, ENST00000915269, ENST00000915270, ENST00000962854, ENST00000962855, ENST00000962856, ENST00000962857, ENST00000998408, ENST00000998409, ENST00000998410, ENST00000998411, ENST00000998412, ENST00000998413, ENST00001048481, ENST00001048482, ENST00001048483, ENST00001083602, ENST00001112758, ENST00001129305, ENST00001129306, ENST00001131884

RefSeq mRNA: 1 — MANE Select: NM_031431 NM_031431

CCDS: CCDS9398

Canonical transcript exons

ENST00000349995 — 23 exons

Exon	Start	End
ENSE00000923374	45476201	45476347
ENSE00000923377	45481230	45481304
ENSE00000923380	45486495	45486575
ENSE00000923389	45516143	45516263
ENSE00001097038	45534702	45536701
ENSE00001097055	45464939	45465210
ENSE00001245412	45518960	45519094
ENSE00001245421	45518762	45518850
ENSE00001245442	45511765	45511854
ENSE00001245511	45483230	45483355
ENSE00001346764	45491412	45491538
ENSE00001346766	45490915	45490958
ENSE00001346776	45482381	45482473
ENSE00001346780	45480125	45480290
ENSE00001346785	45479005	45479066
ENSE00003537948	45493347	45493486
ENSE00003543890	45503244	45503349
ENSE00003572758	45530682	45530780
ENSE00003609786	45509692	45509816
ENSE00003611384	45492159	45492250
ENSE00003645687	45529791	45529918
ENSE00003663293	45496152	45496312
ENSE00003669852	45524976	45525051

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 92.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.3237 / max 334.5969, expressed in 1822 samples.

Highest expression (Bgee): body of pancreas, adrenal tissue, lobe of liver, calcaneal tendon, pancreas.

Genetic regulation across tissues (GTEx eQTL / sQTL)

COG3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 27 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 28 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	4.9e-25	-0.28	13:45492719:A:T
Artery Tibial	eqtl	7.3e-17	-0.26	13:45519694:A:G
Brain Cerebellar Hemisphere	eqtl	3.4e-13	+0.41	13:45525798:T:TAGAG
Brain Cerebellum	eqtl	1.9e-12	+0.46	13:45525798:T:TAGAG
Skin Sun Exposed Lower leg	eqtl	1.4e-10	-0.19	13:45474864:T:G
Skin Not Sun Exposed Suprapubic	eqtl	2.1e-09	-0.22	13:45519694:A:G
Adipose Subcutaneous	eqtl	3.3e-09	+0.24	13:45459255:CTA:C
Nerve Tibial	eqtl	3.2e-07	+0.26	13:45528097:A:C
Esophagus Mucosa	eqtl	9.6e-07	-0.18	13:45519694:A:G
Muscle Skeletal	eqtl	7.0e-05	-0.13	13:45524057:A:G
Breast Mammary Tissue	eqtl	9.4e-05	+0.20	13:45488155:G:A
Brain Cortex	eqtl	6.2e-04	+0.45	13:45468071:G:T
Brain Nucleus accumbens basal ganglia	eqtl	8.9e-04	+0.33	13:45534719:G:A
Esophagus Muscularis	eqtl	1.2e-03	+0.27	13:45520131:C:T
Small Intestine Terminal Ileum	eqtl	1.3e-03	+1.11	13:44673709:C:T
Thyroid	eqtl	1.7e-03	-0.15	13:45513642:G:A
Adipose Visceral Omentum	eqtl	1.9e-03	+0.18	13:45461735:T:C
Brain Spinal cord cervical c-1	eqtl	3.4e-03	+0.39	13:45539184:G:A
Heart Left Ventricle	eqtl	5.5e-03	+0.15	13:45462413:C:G
Brain Frontal Cortex BA9	eqtl	6.4e-03	+0.24	13:45467160:C:T

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
134972	22.1510	1821
134973	1.1446	676
134974	0.0162	7
134975	0.0119	8

Top tissues by expression

showing 100 of 244 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	92.84	gold quality
adrenal tissue	UBERON:0018303	92.27	gold quality
right lobe of liver	UBERON:0001114	91.89	gold quality
calcaneal tendon	UBERON:0003701	91.67	gold quality
pancreas	UBERON:0001264	90.92	gold quality
rectum	UBERON:0001052	90.74	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.18	gold quality
monocyte	CL:0000576	89.93	gold quality
ileal mucosa	UBERON:0000331	89.78	gold quality
granulocyte	CL:0000094	89.66	gold quality
pancreatic ductal cell	CL:0002079	89.61	gold quality
leukocyte	CL:0000738	89.55	gold quality
left adrenal gland cortex	UBERON:0035825	89.43	gold quality
left adrenal gland	UBERON:0001234	89.33	gold quality
right adrenal gland	UBERON:0001233	89.14	gold quality
bone marrow cell	CL:0002092	89.04	gold quality
mucosa of transverse colon	UBERON:0004991	89.01	gold quality
minor salivary gland	UBERON:0001830	88.99	gold quality
adrenal gland	UBERON:0002369	88.89	gold quality
transverse colon	UBERON:0001157	88.86	gold quality
ectocervix	UBERON:0012249	88.85	gold quality
right ovary	UBERON:0002118	88.71	gold quality
right adrenal gland cortex	UBERON:0035827	88.64	gold quality
liver	UBERON:0002107	88.61	gold quality
islet of Langerhans	UBERON:0000006	88.59	gold quality
endocervix	UBERON:0000458	88.57	gold quality
body of stomach	UBERON:0001161	88.54	gold quality
adenohypophysis	UBERON:0002196	88.48	gold quality
left ovary	UBERON:0002119	88.46	gold quality
adrenal cortex	UBERON:0001235	88.40	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.38	gold quality
stomach	UBERON:0000945	88.04	gold quality
left uterine tube	UBERON:0001303	88.04	gold quality
saliva-secreting gland	UBERON:0001044	87.94	gold quality
body of uterus	UBERON:0009853	87.91	gold quality
pituitary gland	UBERON:0000007	87.73	gold quality
mouth mucosa	UBERON:0003729	87.45	gold quality
skin of abdomen	UBERON:0001416	87.44	gold quality
smooth muscle tissue	UBERON:0001135	87.39	gold quality
small intestine	UBERON:0002108	87.39	gold quality
sural nerve	UBERON:0015488	87.21	gold quality
uterine cervix	UBERON:0000002	87.19	gold quality
upper lobe of left lung	UBERON:0008952	87.15	gold quality
gastrocnemius	UBERON:0001388	87.12	gold quality
skin of leg	UBERON:0001511	87.11	gold quality
cerebellar hemisphere	UBERON:0002245	86.99	gold quality
lower esophagus mucosa	UBERON:0035834	86.98	gold quality
cerebellar cortex	UBERON:0002129	86.93	gold quality
intestine	UBERON:0000160	86.86	gold quality
muscle of leg	UBERON:0001383	86.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.80	gold quality
apex of heart	UBERON:0002098	86.75	gold quality
left lobe of thyroid gland	UBERON:0001120	86.73	gold quality
colon	UBERON:0001155	86.72	gold quality
large intestine	UBERON:0000059	86.54	gold quality
right lobe of thyroid gland	UBERON:0001119	86.52	gold quality
esophagus mucosa	UBERON:0002469	86.40	gold quality
descending thoracic aorta	UBERON:0002345	86.38	gold quality
spleen	UBERON:0002106	86.31	gold quality
right atrium auricular region	UBERON:0006631	86.31	gold quality
tibial nerve	UBERON:0001323	86.30	gold quality
thoracic aorta	UBERON:0001515	86.29	gold quality
prostate gland	UBERON:0002367	86.26	gold quality
mucosa of stomach	UBERON:0001199	86.24	gold quality
ascending aorta	UBERON:0001496	86.24	gold quality
secondary oocyte	CL:0000655	86.21	gold quality
cerebellum	UBERON:0002037	86.21	gold quality
upper lobe of lung	UBERON:0008948	86.19	gold quality
stromal cell of endometrium	CL:0002255	86.16	gold quality
right lung	UBERON:0002167	86.16	gold quality
tonsil	UBERON:0002372	86.16	gold quality
metanephros cortex	UBERON:0010533	86.11	gold quality
aorta	UBERON:0000947	86.10	gold quality
popliteal artery	UBERON:0002250	86.09	gold quality
tibial artery	UBERON:0007610	86.09	gold quality
thyroid gland	UBERON:0002046	86.02	gold quality
vermiform appendix	UBERON:0001154	85.82	gold quality
zone of skin	UBERON:0000014	85.81	gold quality
cardiac atrium	UBERON:0002081	85.80	gold quality
omental fat pad	UBERON:0010414	85.64	gold quality
peritoneum	UBERON:0002358	85.63	gold quality
esophagus	UBERON:0001043	85.61	gold quality
left coronary artery	UBERON:0001626	85.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.60	gold quality
right coronary artery	UBERON:0001625	85.42	gold quality
colonic epithelium	UBERON:0000397	85.39	gold quality
corpus callosum	UBERON:0002336	85.14	gold quality
heart left ventricle	UBERON:0002084	85.12	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.07	gold quality
ovary	UBERON:0000992	85.04	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.96	gold quality
heart	UBERON:0000948	84.92	gold quality
adipose tissue of abdominal region	UBERON:0007808	84.86	gold quality
lower esophagus	UBERON:0013473	84.77	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.76	gold quality
cardiac ventricle	UBERON:0002082	84.72	gold quality
coronary artery	UBERON:0001621	84.64	gold quality
vagina	UBERON:0000996	84.63	gold quality
gall bladder	UBERON:0002110	84.62	gold quality
cartilage tissue	UBERON:0002418	84.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.98
E-MTAB-6386	no	251.17

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebellum	tissue	27.9	high
Corpus callosum	tissue	25.5
Putamen	tissue	24.0
Liver	tissue	24.0	medium
Substantia nigra	tissue	23.3
Midbrain	tissue	23.2
Spinal cord	tissue	23.1
Medulla oblongata	tissue	22.9
Thalamus	tissue	22.7
Pons	tissue	22.5
Hypothalamus	tissue	22.4
Septum	tissue	22.4
Hippocampal formation	tissue	22.2
Superior colliculi	tissue	21.8
Ventral forebrain	tissue	21.7
Choroid plexus	tissue	21.6
Periaqueductal gray	tissue	21.5
Cerebral cortex	tissue	21.2	medium
Occipital cortex	tissue	21.2
Motor cortex	tissue	21.1
Entorhinal cortex	tissue	21.0
Somatosensory cortex	tissue	20.7
Retrosplenial cortex	tissue	20.3
Amygdala	tissue	20.1
Insular cortex	tissue	20.1
Retrosplenial and cingulate cortex	tissue	19.8
Temporal cortex	tissue	19.7
Prefrontal cortex	tissue	19.5
Basal ganglia	tissue	19.2	medium
Olfactory bulb	tissue	19.2
Rectum	tissue	17.7	high
Prostate	tissue	17.6	high
Salivary gland	tissue	17.0	high
Pancreas	tissue	15.9	high
Thyroid gland	tissue	15.9	high
Epididymis	tissue	15.8	high
Colon	tissue	15.2	high
Nucleus accumbens	tissue	15.0
Breast	tissue	14.6	medium
Pituitary gland	tissue	14.1
Stomach 1	tissue	13.9	high
Cervix	tissue	13.6	medium
Postcentral gyrus	tissue	13.5
Hippocampus	tissue	13.1	medium
Caudate putamen	tissue	12.8
Ovary	tissue	12.7	high
Frontal cortex	tissue	12.6
Adrenal gland	tissue	12.6	high
Vagina	tissue	12.4	medium
Endometrium 1	tissue	12.2	medium
Placenta	tissue	12.2	high
Small intestine	tissue	12.2	high
Duodenum	tissue	11.8	high
Skin 1	tissue	11.6	low
Seminal vesicle	tissue	11.6	high
Parathyroid gland	tissue	11.5	high
Kidney	tissue	11.5	medium
Locus coeruleus	tissue	11.5
Thymus	tissue	11.4
Smooth muscle	tissue	11.3	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — White matter (25.5), Dorsal spinal cord (23.1), Ventral spinal cord (23.1), Dorsal hippocampus (22.2), Subiculum (21.5).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting COG3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 99 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.314, missense Z 1.86 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000349995 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
13:45,465,037–45,491,538	424 / 430.6	0.98	no
13:45,492,159–45,534,728	389 / 542.6	0.72	no
DepMap (CRISPR cell-line fitness): dependent in 89.2% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): COV362 (-2.256), SNB75 (-2.2), SNU-423 (-1.88), SNU-449 (-1.844), SNU-182 (-1.837), Li-7 (-1.826), KMS-20 (-1.8), SNU-216 (-1.793), A-172 (-1.79), G-292, clone A141B1 (-1.787), TUHR10TKB (-1.779), SK-LMS-1 (-1.778), NCI-H2030 (-1.758), NCI-H2887 (-1.754), 769-P (-1.745).

Literature-anchored findings (GeneRIF, showing 2)

• Sec34 is implicated in traffic from the endoplasmic reticulum to the Golgi and exists in a complex with GTC-90 and ldlBp (PMID:11929878)
• Biallelic missense variants in COG3 cause a congenital disorder of glycosylation with impairment of retrograde vesicular trafficking. (PMID:37711075)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cog3	ENSDARG00000101999
mus_musculus	Cog3	ENSMUSG00000034893
rattus_norvegicus	Cog3	ENSRNOG00000000155
drosophila_melanogaster	Cog3	FBGN0031536
caenorhabditis_elegans	cogc-3	WBGENE00022121

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2450151) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal lens morphology	1
increased circulating insulin level	1
preweaning lethality, complete penetrance	1

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
Drosophila pseudoobscura pseudoobscura	Q29N70	86.2%	Diamond
Aedes aegypti	Q16ZN9	59.2%	Diamond
Arabidopsis thaliana	F4HQ84	35.7%	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
LINC01055	ncRNA	103752581
ERICH6B	protein-coding	220081
TPT1-AS1	ncRNA	100190939
SLC25A30	protein-coding	253512
SLC25A30-AS1	ncRNA	100874259

Protein

Protein identifiers

Conserved oligomeric Golgi complex subunit 3 — Q96JB2 (reviewed: Q96JB2)

Alternative names: Component of oligomeric Golgi complex 3, Vesicle-docking protein SEC34 homolog, p94

All UniProt accessions (4): A0A087WTH9, A0A087WYY9, B4DH72, Q96JB2

UniProt curated annotations — full annotation on UniProt →

Function. Involved in ER-Golgi transport. Also involved in retrograde (Golgi to ER) transport.

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. Interacts with TMEM115.

Subcellular location. Golgi apparatus. Golgi stack membrane.

Tissue specificity. Widely expressed with highest levels in pancreas and testis and lowest levels in lung.

Disease relevance. Congenital disorder of glycosylation 2BB (CDG2BB) [MIM:620546] A multisystem disorder 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. CDG2BB is an autosomal recessive form characterized by global developmental delay, severe intellectual disability, microcephaly, epilepsy, facial dysmorphism, and variable neurological findings. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the COG3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96JB2-1	1	yes
Q96JB2-2	2

RefSeq proteins (1): NP_113619* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007265	COG_su3	Family
IPR048320	COG3_N	Domain
IPR048685	COG3_C	Domain

Pfam: PF04136, PF20671

UniProt features (14 total): sequence variant 4, sequence conflict 2, modified residue 2, splice variant 2, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JB2-F1	78.82	0.39

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; plasma membrane; cytosol; nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

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

Post-translational modifications (2)

Type	Positions
N-acetylalanine	2
Phosphoserine	663

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: 176 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_INTRA_GOLGI_VESICLE_MEDIATED_TRANSPORT, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOCC_TRANS_GOLGI_NETWORK, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_PROTEIN_STABILIZATION, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_STABILITY, HTF_01, AACTTT_UNKNOWN, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, DING_LUNG_CANCER_EXPRESSION_BY_COPY_NUMBER

GO Biological Process (10): retrograde transport, vesicle recycling within Golgi (GO:0000301), 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), Golgi organization (GO:0007030), glycoprotein biosynthetic process (GO:0009101), protein localization to organelle (GO:0033365), protein stabilization (GO:0050821), protein transport (GO:0015031)

GO Molecular Function (2): cargo adaptor activity (GO:0140312), protein binding (GO:0005515)

GO Cellular Component (9): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), cis-Golgi network (GO:0005801), cytosol (GO:0005829), plasma membrane (GO:0005886), COG complex (GO:0017119), Golgi cisterna membrane (GO:0032580), 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

28 GO namespaces:

Category	Terms
intracellular protein localization	3
cytoplasm	3
Golgi vesicle transport	3
Golgi apparatus	3
intracellular transport	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
organelle membrane	2
intra-Golgi vesicle-mediated transport	1
protein transport	1
organelle organization	1
endomembrane system organization	1
macromolecule biosynthetic process	1
glycoprotein metabolic process	1
carbohydrate derivative biosynthetic process	1
regulation of protein stability	1
transport	1
establishment of protein localization	1
vesicle-mediated transport	1
protein-macromolecule adaptor activity	1
binding	1
bounding membrane of organelle	1
endomembrane system	1
membrane	1
cell periphery	1
vesicle tethering complex	1
Golgi cisterna	1
trans-Golgi network	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 12 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

12 experimentally-supported GO terms:

GO term	NS	Evidence
Golgi organization	BP	mutant phenotype
endoplasmic reticulum to Golgi vesicle-mediated transport	BP	direct assay
glycoprotein biosynthetic process	BP	mutant phenotype
intra-Golgi vesicle-mediated transport	BP	direct assay
protein localization to organelle	BP	mutant phenotype
protein stabilization	BP	mutant phenotype
retrograde transport, vesicle recycling within Golgi	BP	mutant phenotype
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	BP	mutant phenotype
COG complex	CC	direct assay
Golgi apparatus	CC	direct assay
cytosol	CC	direct assay
plasma membrane	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,625 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COG3	COG2	Q14746	985
COG3	COG1	Q8WTW3	984
COG3	COG7	P83436	980
COG3	COG5	Q9UP83	977
COG3	COG8	Q96MW5	966
COG3	COG4	Q9H9E3	952
COG3	COG6	Q9Y2V7	945
COG3	GOSR2	O14653	765
COG3	COPB1	P53618	749
COG3	STX5	Q13190	711
COG3	RIC1	Q4ADV7	710
COG3	BLCAP	P62952	660
COG3	TGOLN2	O43493	651
COG3	VPS53	Q5VIR6	646
COG3	BET1	O15155	633

IntAct

Human interaction partners of COG3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
COG7	association	0.640	3
TBCC	association	0.530	1

BioGRID (199 interactions; top human partners by supporting records): COG1 (Affinity Capture-MS; 8 records), COG2 (Affinity Capture-MS; 8 records), COG7 (Affinity Capture-MS; 8 records), COG4 (Affinity Capture-MS; 7 records), COG6 (Affinity Capture-MS; 7 records), COG5 (Affinity Capture-MS; 6 records), COG8 (Affinity Capture-MS; 6 records), BSG (Affinity Capture-MS; 3 records), CCDC18 (Affinity Capture-MS; 3 records), CD274 (Affinity Capture-MS; 3 records), CEP250 (Affinity Capture-MS; 3 records), HAUS3 (Affinity Capture-MS; 3 records), HAUS4 (Affinity Capture-MS; 3 records), RAB1B (Synthetic Lethality; 3 records), SCN2B (Affinity Capture-MS; 3 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
COG3	“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 COG3: 117 ClinVar records (1 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	89
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Showing all 1 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
3391853	GRCh37/hg19 13q11-31.3(chr13:19436287-92292639)x3	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore COG3’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; 31 predictions of 2,376):

Position(s)	Effect	Δscore	Sites
13:45465206	donor_gain	1.0000
13:45465211–45465212	donor_loss	1.0000	5
13:45476199	acceptor_gain	1.0000
13:45476199–45476200	acceptor_loss	1.0000	4
13:45476348–45476349	donor_loss	1.0000	5
13:45479003–45479004	acceptor_loss	1.0000	5
13:45479067–45479068	donor_loss	1.0000	5
13:45481220–45481224	acceptor_gain	1.0000	3
13:45481228	acceptor_gain	1.0000
13:45482379	acceptor_gain	1.0000

AlphaMissense

1,752 missense substitutions predicted likely pathogenic (of 5,433 scored), across 490 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
M495	9	0.916	0.992
M553	9	0.906	0.996
D459	8	0.994	0.998
D485	8	0.993	0.998
F577	8	0.989	0.999
F626	8	0.984	0.999
D690	8	0.981	0.997
F611	8	0.978	0.999
H615	8	0.969	0.998
D684	8	0.966	0.987
D379	8	0.960	0.988
D549	8	0.952	0.983
F388	8	0.951	0.993
H419	8	0.937	0.989
F670	8	0.928	0.996
H551	8	0.926	0.993
F293	8	0.895	0.986
D230	8	0.882	0.966
H173	8	0.867	0.986
F449	8	0.864	0.983

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	2.37e-05
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	0.000429

Disease associations

OMIM: gene MIM:606975 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
congenital disorder of glycosylation, type IIbb	Limited	Autosomal recessive

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
congenital disorder of glycosylation	Limited	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (10 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

10 panels:

Panel	Rating
Congenital disorders of glycosylation	amber
Early onset or syndromic epilepsy	amber
Hereditary ataxia and cerebellar anomalies, childhood onset	amber
Hypotonic infant	amber
Intellectual disability	amber
Leukodystrophy, childhood onset	amber
Likely inborn error of metabolism	amber
Paediatric disorders	amber
Severe microcephaly	amber
Unexplained death in infancy and sudden unexplained death in childhood	amber

Mondo (1): congenital disorder of glycosylation, type IIbb (MONDO:0957820)

HPO phenotypes

33 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000233	Thin vermilion border
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000448	Prominent nose
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000639	Nystagmus
HP:0000718	Aggressive behavior
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001344	Absent speech
HP:0002188	Delayed CNS myelination
HP:0002353	EEG abnormality
HP:0003160	Abnormal isoelectric focusing of serum transferrin
HP:0003202	Skeletal muscle atrophy
HP:0003593	Infantile onset
HP:0006855	Cerebellar vermis atrophy
HP:0008936	Axial hypotonia
HP:0011463	Childhood onset
HP:0012389	Appendicular hypotonia
HP:0032792	Tonic seizure
HP:0032794	Myoclonic seizure
HP:0033725	Thin corpus callosum
HP:0034392	Joint contracture

GWAS associations

2 associations:

Study	Trait	p-value
GCST005586_4	Breast milk fatty acid composition (maternal genotype effect)	2e-10
GCST005587_4	Breast milk fatty acid composition (infant genotype effect)	5e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0005939	parental genotype effect measurement
EFO:0007959	fetal genotype effect measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105842 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation, decreases expression, increases expression, affects cotreatment	3
sodium arsenite	decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	increases expression	2
dicrotophos	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
arsenic disulfide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
ICG 001	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
jinfukang	decreases expression	1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)	increases expression	1
NSC668394	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects binding, increases reaction	1
Formaldehyde	increases expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Rotenone	decreases expression	1
Dronabinol	decreases expression	1
Thiram	increases expression	1
Tunicamycin	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4012602	Binding	Binding affinity to COG3 in human INA-6 cells after 3 hrs by nanoLC-MS/MS method	Ugi Reaction-Derived α-Acyl Aminocarboxamides Bind to Phosphatidylinositol 3-Kinase-Related Kinases, Inhibit HSF1-Dependent Heat Shock Response, and Induce Apoptosis in Multiple Myeloma Cells. — *J Med Chem*

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for COG3 across ~30M SureChEMBL compounds — explore on Sugi Predict.