COG7

Summary

COG7 (component of oligomeric golgi complex 7, HGNC:18622) is a protein-coding gene on chromosome 16p12.2, encoding Conserved oligomeric Golgi complex subunit 7 (P83436). Required for normal Golgi function. It is a selective cancer dependency (DepMap: 20.7% of cell lines).

The protein encoded by this gene resides in the golgi, and constitutes one of the 8 subunits of the conserved oligomeric Golgi (COG) complex, which is required for normal golgi morphology and localization. Mutations in this gene are associated with the congenital disorder of glycosylation type IIe.

Source: NCBI Gene 91949 — RefSeq curated summary.

At a glance

• Gene–disease (curated): COG7-congenital disorder of glycosylation (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 626 total — 18 pathogenic, 9 likely-pathogenic (top 5% of genes corpus-wide)
• GTEx eGene: eQTL in 13 tissues, sQTL in 47 (q < 0.05)
• Phenotypes (HPO): 73
• Cancer dependency (DepMap): dependent in 20.7% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.65 (unconstrained)
• MANE Select transcript: NM_153603

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18622
Approved symbol	COG7
Name	component of oligomeric golgi complex 7
Location	16p12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000168434
Ensembl biotype	protein_coding
OMIM	606978
Entrez	91949

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 17 protein_coding, 7 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000307149

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

ENST00000307149, ENST00000561854, ENST00000563164, ENST00000566364, ENST00000567821, ENST00000569635, ENST00000887421, ENST00000887422, ENST00000887423, ENST00000887424, ENST00000887425, ENST00000916650, ENST00000916651, ENST00000941094, ENST00000941095, ENST00000941096, ENST00000941097, ENST00001006955, ENST00001024344, ENST00001064377, ENST00001064378, ENST00001064379, ENST00001064380, ENST00001118072, ENST00001118073, ENST00001129672, ENST00001136024

RefSeq mRNA: 1 — MANE Select: NM_153603 NM_153603

CCDS: CCDS10610

Canonical transcript exons

ENST00000307149 — 17 exons

Exon	Start	End
ENSE00001177155	23416967	23417121
ENSE00001177162	23418700	23418827
ENSE00001177170	23424749	23424947
ENSE00001177177	23433545	23433667
ENSE00001177180	23434636	23434718
ENSE00001177185	23442477	23442645
ENSE00001177192	23445048	23445164
ENSE00001177200	23445813	23445961
ENSE00001283250	23393233	23393347
ENSE00001310303	23452826	23453189
ENSE00001857775	23388493	23389086
ENSE00003472495	23410295	23410360
ENSE00003503765	23392380	23392523
ENSE00003524083	23398046	23398129
ENSE00003556111	23406076	23406262
ENSE00003567633	23403694	23403834
ENSE00003635741	23413448	23413564

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 95.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.2875 / max 95.5856, expressed in 1783 samples.

Highest expression (Bgee): uterine tube, adenohypophysis, pituitary gland, lower esophagus mucosa, endocervix.

Genetic regulation across tissues (GTEx eQTL / sQTL)

COG7 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 13 tissues and its splicing (sQTL) in 47 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 60 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	sqtl	5.9e-42	+0.86	16:23391710:T:A
Thyroid	sqtl	1.2e-41	+0.73	16:23392189:G:A
Nerve Tibial	sqtl	6.3e-40	+0.91	16:23385792:T:C
Testis	sqtl	1.6e-37	+1.03	16:23400516:G:A
Cells EBV-transformed lymphocytes	sqtl	5.9e-31	+1.03	16:23385792:T:C
Skin Not Sun Exposed Suprapubic	sqtl	6.3e-30	-0.74	16:23385792:T:C
Lung	sqtl	1.4e-29	-0.54	16:23392189:G:A
Colon Sigmoid	sqtl	5.6e-28	+0.85	16:23392189:G:A
Pituitary	sqtl	5.6e-27	+0.91	16:23400516:G:A
Muscle Skeletal	sqtl	1.5e-26	+0.68	16:23392189:G:A
Colon Transverse	sqtl	3.3e-26	+0.72	16:23385792:T:C
Cells Cultured fibroblasts	eqtl	5.4e-26	+0.34	16:23392189:G:A
Artery Tibial	sqtl	1.1e-24	+0.69	16:23385792:T:C
Esophagus Muscularis	sqtl	3.2e-23	+0.68	16:23385792:T:C
Adipose Subcutaneous	sqtl	1.5e-22	+0.66	16:23392189:G:A
Breast Mammary Tissue	sqtl	2.4e-21	+0.75	16:23392189:G:A
Whole Blood	sqtl	7.7e-21	+0.57	16:23385792:T:C
Prostate	sqtl	4.7e-20	+0.88	16:23400783:T:A
Esophagus Mucosa	sqtl	5.7e-20	+0.58	16:23400783:T:A
Heart Atrial Appendage	sqtl	2.6e-19	+0.67	16:23385792:T:C

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
156770	9.2875	1783

Top tissues by expression

showing 100 of 288 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	95.52	gold quality
adenohypophysis	UBERON:0002196	94.16	gold quality
pituitary gland	UBERON:0000007	94.10	gold quality
lower esophagus mucosa	UBERON:0035834	91.75	gold quality
endocervix	UBERON:0000458	91.64	gold quality
right lobe of thyroid gland	UBERON:0001119	91.64	gold quality
left lobe of thyroid gland	UBERON:0001120	91.09	gold quality
apex of heart	UBERON:0002098	91.01	gold quality
mucosa of transverse colon	UBERON:0004991	90.84	gold quality
thyroid gland	UBERON:0002046	90.61	gold quality
bronchial epithelial cell	CL:0002328	90.58	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.41	gold quality
epithelium of bronchus	UBERON:0002031	90.31	gold quality
bronchus	UBERON:0002185	90.27	gold quality
ectocervix	UBERON:0012249	90.14	gold quality
trachea	UBERON:0003126	89.72	gold quality
right ovary	UBERON:0002118	89.65	gold quality
left ovary	UBERON:0002119	89.53	gold quality
metanephros cortex	UBERON:0010533	89.46	gold quality
transverse colon	UBERON:0001157	89.35	gold quality
body of uterus	UBERON:0009853	89.15	gold quality
minor salivary gland	UBERON:0001830	88.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.91	gold quality
body of stomach	UBERON:0001161	88.88	gold quality
right frontal lobe	UBERON:0002810	88.84	gold quality
skin of abdomen	UBERON:0001416	88.79	gold quality
nucleus accumbens	UBERON:0001882	88.76	gold quality
skin of leg	UBERON:0001511	88.70	gold quality
fundus of stomach	UBERON:0001160	88.67	gold quality
granulocyte	CL:0000094	88.55	gold quality
prostate gland	UBERON:0002367	88.53	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.39	gold quality
caudate nucleus	UBERON:0001873	88.32	gold quality
amygdala	UBERON:0001876	88.28	gold quality
tibial nerve	UBERON:0001323	88.27	gold quality
left uterine tube	UBERON:0001303	88.14	gold quality
right adrenal gland	UBERON:0001233	88.11	gold quality
anterior cingulate cortex	UBERON:0009835	88.10	gold quality
right adrenal gland cortex	UBERON:0035827	88.06	gold quality
cingulate cortex	UBERON:0003027	88.05	gold quality
putamen	UBERON:0001874	87.76	gold quality
left adrenal gland cortex	UBERON:0035825	87.75	gold quality
stromal cell of endometrium	CL:0002255	87.72	gold quality
adrenal cortex	UBERON:0001235	87.69	gold quality
saliva-secreting gland	UBERON:0001044	87.67	gold quality
spinal cord	UBERON:0002240	87.64	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.57	gold quality
left adrenal gland	UBERON:0001234	87.55	gold quality
stomach	UBERON:0000945	87.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.46	gold quality
mouth mucosa	UBERON:0003729	87.44	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.36	gold quality
esophagus mucosa	UBERON:0002469	87.30	gold quality
lower esophagus	UBERON:0013473	87.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.25	gold quality
right coronary artery	UBERON:0001625	87.23	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.16	gold quality
esophagus	UBERON:0001043	87.05	gold quality
mucosa of stomach	UBERON:0001199	87.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.01	gold quality
colon	UBERON:0001155	86.97	gold quality
renal medulla	UBERON:0000362	86.93	gold quality
cerebellar hemisphere	UBERON:0002245	86.90	gold quality
lateral globus pallidus	UBERON:0002476	86.86	gold quality
large intestine	UBERON:0000059	86.82	gold quality
body of pancreas	UBERON:0001150	86.82	gold quality
cerebellar cortex	UBERON:0002129	86.82	gold quality
rectum	UBERON:0001052	86.81	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.80	gold quality
pylorus	UBERON:0001166	86.78	gold quality
right atrium auricular region	UBERON:0006631	86.78	gold quality
zone of skin	UBERON:0000014	86.67	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.58	gold quality
right lobe of liver	UBERON:0001114	86.53	gold quality
upper lobe of left lung	UBERON:0008952	86.47	gold quality
adrenal gland	UBERON:0002369	86.38	gold quality
intestine	UBERON:0000160	86.36	gold quality
spleen	UBERON:0002106	86.32	gold quality
right testis	UBERON:0004534	86.16	gold quality
forebrain	UBERON:0001890	85.95	gold quality
ventricular zone	UBERON:0003053	85.93	gold quality
left testis	UBERON:0004533	85.93	gold quality
vagina	UBERON:0000996	85.92	gold quality
ascending aorta	UBERON:0001496	85.91	gold quality
pharyngeal mucosa	UBERON:0000355	85.84	gold quality
hypothalamus	UBERON:0001898	85.81	gold quality
cerebellum	UBERON:0002037	85.78	gold quality
thoracic aorta	UBERON:0001515	85.71	gold quality
nasal cavity epithelium	UBERON:0005384	85.70	gold quality
right lung	UBERON:0002167	85.67	gold quality
cardiac atrium	UBERON:0002081	85.62	gold quality
ovary	UBERON:0000992	85.61	gold quality
heart left ventricle	UBERON:0002084	85.60	gold quality
brain	UBERON:0000955	85.58	gold quality
aorta	UBERON:0000947	85.56	gold quality
nasal cavity mucosa	UBERON:0001826	85.55	gold quality
small intestine	UBERON:0002108	85.49	gold quality
popliteal artery	UBERON:0002250	85.47	gold quality
tibial artery	UBERON:0007610	85.47	gold quality
cardiac ventricle	UBERON:0002082	85.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.04
E-ENAD-17	no	654.69

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	37.3
Caudate putamen	tissue	32.4
Frontal cortex	tissue	30.3
Corpus callosum	tissue	27.8
Cerebral cortex	tissue	25.2	high
Insular cortex	tissue	25.2
Hippocampal formation	tissue	24.9
Amygdala	tissue	24.5
Hypothalamus	tissue	24.4
Cerebellum	tissue	24.0	not detected
Somatosensory cortex	tissue	24.0
Ventral forebrain	tissue	23.9
Retrosplenial and cingulate cortex	tissue	23.8
Basal ganglia	tissue	23.7	high
Septum	tissue	23.6
Retrosplenial cortex	tissue	23.4
Occipital cortex	tissue	23.4
Prefrontal cortex	tissue	23.2
Entorhinal cortex	tissue	23.1
Temporal cortex	tissue	23.0
Periaqueductal gray	tissue	22.9
Olfactory bulb	tissue	22.9
Midbrain	tissue	22.8
Motor cortex	tissue	22.6
Putamen	tissue	22.5
Medulla oblongata	tissue	22.4
Pituitary gland	tissue	22.3
Pons	tissue	22.3
Thalamus	tissue	22.3
Spinal cord	tissue	21.9
Superior colliculi	tissue	21.6
Substantia nigra	tissue	21.1
Nucleus accumbens	tissue	19.1
Hippocampus	tissue	18.7	high
Locus coeruleus	tissue	17.9
Postcentral gyrus	tissue	17.2
Parathyroid gland	tissue	15.4	medium
Fallopian tube	tissue	14.2	medium
Retina	tissue	12.8
Salivary gland	tissue	12.1	low
Stomach 1	tissue	12.0	medium
Vagina	tissue	11.7	low
Skin 1	tissue	11.5	low
Thyroid gland	tissue	11.2	medium
Prostate	tissue	11.2	medium
Rectum	tissue	11.1	high
Epididymis	tissue	10.6	medium
Cervix	tissue	10.1	medium
Colon	tissue	10.0	high
Seminal vesicle	tissue	9.8	medium
Kidney	tissue	9.8	medium
Bone marrow	tissue	9.3	medium
Breast	tissue	9.1	high
Ovary	tissue	8.6	medium
Skeletal muscle	tissue	8.4	not detected
Smooth muscle	tissue	8.1	not detected
Pancreas	tissue	8.0	high
Heart muscle	tissue	7.9	not detected
Gallbladder	tissue	7.9	high
Lung	tissue	7.8	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — White matter (27.8), Ventral hippocampus (24.9), Subiculum (23.9), Parieto-temporal junction (white matter) (23.4), Dorsal hippocampus (23.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting COG7 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

28 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-3691-3P	97.90	65.97	791
HSA-MIR-3151-3P	97.80	66.16	479
HSA-MIR-6131	97.22	66.72	960
HSA-MIR-635	96.00	65.54	687
HSA-MIR-6774-5P	95.94	65.18	722

Functional genomics

gnomAD constraint: pLI 2.56e-05, LOEUF 0.651, missense Z 1.3 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000307149 — one region, missense o/e 0.93. ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 20.7% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): SK-PN-DW (-1.404), 769-P (-1.363), HSC-39 (-1.237), HuH-6 (-1.193), Li-7 (-1.158), Hs 944.T (-1.138), 94T778 (-1.125), C80 (-1.117), CME-1 (-1.105), ABC-1 (-1.103), CAL-29 (-1.088), KKU-213 (-1.077), JIMT-1 (-1.051), UM-UC9 (-1.041), D425 (-1.025).

Literature-anchored findings (GeneRIF, showing 7)

• COG5- and COG7 subunits play distinctive roles in controlling Golgi structure and function (PMID:16051600)
• Retrograde transport of multiple Golgi proteins to the ER in COG-7-deficient patient fibroblasts via brefeldin A-induced tubules was significantly slower than occurs in normal fibroblasts. (PMID:16510524)
• A homozygous, intronic splice site mutation (c.169+4A>C) of the COG7 gene was identified in 3 patients with Congenital Disorder of Glycosylation type IIe. (PMID:17356545)
• A new mutation in COG7 extends the spectrum of COG subunit deficiencies. (PMID:19577670)
• Targeted silencing of components of lobe B of the COG complex, namely COG5, COG6, COG7 and COG8, inhibited HIV-1 replication (PMID:25179963)
• Cog5-Cog7 crystal structure reveals interactions essential for the function of a multisubunit tethering complex. (PMID:25331899)
• TMEM-COG4, COG7 and COG8 subunits restore endogenous COG localization to the Golgi membranes (PMID:29467253)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cog7	ENSDARG00000061372
mus_musculus	Cog7	ENSMUSG00000034951
rattus_norvegicus	Cog7	ENSRNOG00000060008
drosophila_melanogaster	Cog7	FBGN0051040

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2685013) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal sinus arrhythmia	1
cornea deposits	1
impaired pupillary reflex	1
preweaning lethality, complete penetrance	1
embryonic lethality prior to organogenesis	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
Bos taurus	A2VDR8	92.1%	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
EARS2	protein-coding	124454
GGA2	protein-coding	23062
NDUFAB1	protein-coding	4706
UBFD1	protein-coding	56061
SCNN1B	protein-coding	6338
SCNN1G	protein-coding	6340
USP31	protein-coding	57478

Protein

Protein identifiers

Conserved oligomeric Golgi complex subunit 7 — P83436 (reviewed: P83436)

Alternative names: Component of oligomeric Golgi complex 7

All UniProt accessions (4): A0A0S2Z652, P83436, I3L2R8, I3L337

UniProt curated annotations — full annotation on UniProt →

Function. Required for normal Golgi 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 2E (CDG2E) [MIM:608779] 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the COG7 family.

RefSeq proteins (1): NP_705831* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019335	COG7	Family

Pfam: PF10191

UniProt features (2 total): chain 1, sequence variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P83436-F1	82.77	0.30

Human Protein Atlas

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

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus

Antibody reliability (HPA): IH uncertain · IF supported

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: 236 (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_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_PROTEIN_STABILIZATION, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_STABILITY, BALLIF_DEVELOPMENTAL_DISABILITY_P16_P12_DELETION, GOBP_PROTEIN_LOCALIZATION_TO_GOLGI_APPARATUS, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, MORF_IL9, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS

GO Biological Process (9): retrograde transport, vesicle recycling within Golgi (GO:0000301), intracellular protein transport (GO:0006886), retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), Golgi organization (GO:0007030), glycoprotein biosynthetic process (GO:0009101), protein localization to organelle (GO:0033365), protein localization to Golgi apparatus (GO:0034067), protein stabilization (GO:0050821), protein transport (GO:0015031)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), COG complex (GO:0017119), trans-Golgi network membrane (GO:0032588)

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

23 GO namespaces:

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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 14 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
Golgi organization	BP	mutant phenotype
glycoprotein biosynthetic process	BP	mutant phenotype
intracellular protein transport	BP	mutant phenotype
protein localization to Golgi apparatus	BP	mutant phenotype
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

Protein interactions and networks

STRING

showing 15 of 1,124 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COG7	COG5	Q9UP83	985
COG7	COG1	Q8WTW3	983
COG7	COG2	Q14746	983
COG7	COG3	Q96JB2	980
COG7	COG8	Q96MW5	967
COG7	COG4	Q9H9E3	946
COG7	COG6	Q9Y2V7	944
COG7	STX5	Q13190	697
COG7	GOSR2	O14653	673
COG7	COPB1	P53618	654
COG7	RIC1	Q4ADV7	645
COG7	VPS52	Q8N1B4	645
COG7	VPS54	Q9P1Q0	634
COG7	VPS53	Q5VIR6	632
COG7	STX16	O14662	617

IntAct

Human interaction partners of COG7 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

11 partners by confidence:

Partner	Interaction type	MIscore	Records
TAX1BP1	physical association	0.850	10
KIFC3	physical association	0.720	6
COG4	physical association	0.670	3
COG3	association	0.640	3
ILVBL	association	0.640	3
MEOX2	physical association	0.560	3
COG5	physical association	0.560	2
COG2	association	0.530	1
SCFD1	association	0.460	2
POC1B	association	0.350	1
TRAF5	association	0.350	1

BioGRID (139 interactions; top human partners by supporting records): COG5 (Co-fractionation; 10 records), COG3 (Affinity Capture-MS; 8 records), COG4 (Co-fractionation; 6 records), COG6 (Co-fractionation; 5 records), COG1 (Co-fractionation; 4 records), COG2 (Co-fractionation; 4 records), BSG (Affinity Capture-MS; 3 records), CA14 (Affinity Capture-MS; 3 records), CD274 (Affinity Capture-MS; 3 records), COG8 (Affinity Capture-MS; 3 records), DTNBP1 (Affinity Capture-MS; 3 records), TAX1BP1 (Two-hybrid; 3 records), TRAF5 (Affinity Capture-MS; 3 records), VSIG2 (Affinity Capture-MS; 3 records), COMMD8 (Affinity Capture-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
COG7	“form complex”	“COG tethering complex”	binding

Protein complexes (CORUM) (5)

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

5 complexes by size:

Complex	Subunits	Members
COG complex	8	COG2, COG3, COG4, COG5, COG6, COG7, COG8, COG1
COG1-COG8-COG5-COG6-COG7 subcomplex	5	COG1, COG5, COG6, COG7, COG8
COG subcomplex (COG5, COG6, COG7, COG8)	4	COG5, COG6, COG7, COG8
COG5-COG6-COG7 subcomplex	3	COG5, COG6, COG7
COG subcomplex (COG5, COG7)	2	COG5, COG7

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 11 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.

GO biological processes:

GO term	Partners	Fold	FDR
Golgi organization	5	66.9×	2e-07

Disease & clinical

Genetic variants

Variant evidence for COG7: 626 ClinVar records (27 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	9
Uncertain significance	239
Likely benign	269
Benign	28

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 27 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
196587	NM_153603.4(COG7):c.323dup (p.Leu108fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1676422	NM_153603.4(COG7):c.318+1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3650	NM_153603.4(COG7):c.169+4A>C	Pathogenic	criteria provided, single submitter	2
489365	NM_153603.4(COG7):c.1321C>T (p.Gln441Ter)	Pathogenic	criteria provided, single submitter	1
548708	NM_153603.4(COG7):c.1476-1G>T	Pathogenic	criteria provided, single submitter	1
2004610	NM_153603.4(COG7):c.1375del (p.Gln459fs)	Pathogenic	criteria provided, single submitter	1
2113880	NM_153603.4(COG7):c.698del (p.Leu232_Leu233insTer)	Pathogenic	criteria provided, single submitter	1
2120057	NM_153603.4(COG7):c.1255dup (p.Cys419fs)	Pathogenic	criteria provided, single submitter	1
2773270	NM_153603.4(COG7):c.1784T>A (p.Leu595Ter)	Pathogenic	criteria provided, single submitter	1
2775952	NM_153603.4(COG7):c.1498dup (p.Tyr500fs)	Pathogenic	criteria provided, single submitter	1
2813995	NM_153603.4(COG7):c.1808G>A (p.Trp603Ter)	Pathogenic	criteria provided, single submitter	1
3615091	NM_153603.4(COG7):c.1702C>T (p.Arg568Ter)	Pathogenic	criteria provided, single submitter	1
3656005	NM_153603.4(COG7):c.343_344insTCCCTCTCCCTCTCCCGTCTCCCTCTCCCTCTCCCGTCTCCCGCTCCCTCTCCCGGCTCCCGCTCCCGCTCCCGGGGCCCTCTCCCGCGCGCGGCNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAGAAATTGACCAAGTGA (p.Lys115delinsIleProLeuProLeuProSerProSerProSerProValSerArgSerLeuSerArgLeuProLeuProLeuProGlyProSerProAlaArgGlyXaaXaaXaaXaaLysLysLysLysLysLysArgAsnTer)	Pathogenic	criteria provided, single submitter	1
3671796	NM_153603.4(COG7):c.79G>T (p.Glu27Ter)	Pathogenic	criteria provided, single submitter	1
4715337	NM_153603.4(COG7):c.669C>A (p.Tyr223Ter)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore COG7’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 1,563):

Position(s)	Effect	Δscore	Sites
16:23389088	acceptor_loss	1.0000	2
16:23392419	donor_gain	1.0000
16:23392524–23392525	acceptor_loss	1.0000	6
16:23393231–23393232	donor_loss	1.0000	3
16:23393348–23393349	acceptor_loss	1.0000	3
16:23403835–23403836	acceptor_loss	1.0000	6
16:23403842	acceptor_gain	1.0000
16:23406074–23406075	donor_loss	1.0000	4
16:23406150	donor_gain	1.0000
16:23413446–23413447	donor_loss	1.0000	4

AlphaMissense

1,669 missense substitutions predicted likely pathogenic (of 5,085 scored), across 483 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
M42	9	0.849	0.992
D714	8	0.991	0.997
F6	8	0.973	0.998
F11	8	0.969	0.997
F211	8	0.958	0.992
F272	8	0.944	0.981
D2	8	0.919	0.980
F619	8	0.919	0.996
N182	8	0.914	0.988
D129	8	0.912	0.976
D679	8	0.906	0.973
F587	8	0.905	0.984
N18	8	0.902	0.987
D112	8	0.901	0.966
F21	8	0.891	0.977
F465	8	0.886	0.978
F196	8	0.847	0.989
M690	8	0.817	0.973
F324	8	0.808	0.952
D93	8	0.800	0.934

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	4.47e-06
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000131

Disease associations

OMIM: gene MIM:606978 | disease phenotypes: MIM:608779

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
COG7-congenital disorder of glycosylation	Definitive	Autosomal recessive	4

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
COG7-congenital disorder of glycosylation	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (14 panels, 14 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

14 panels:

Panel	Rating
Cholestasis	green
Congenital disorders of glycosylation	green
DDG2P	green
Early onset or syndromic epilepsy	green
Fetal anomalies	green
Hereditary ataxia and cerebellar anomalies, childhood onset	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Neonatal cholestasis	green
Paediatric disorders	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (1): COG7-congenital disorder of glycosylation (MONDO:0012118)

Orphanet (1): COG7-CDG (Orphanet:79333)

HPO phenotypes

showing 60 of 73 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000077	Abnormality of the kidney
HP:0000126	Hydronephrosis
HP:0000160	Narrow mouth
HP:0000253	Progressive microcephaly
HP:0000278	Retrognathia
HP:0000294	Low anterior hairline
HP:0000319	Smooth philtrum
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000445	Wide nose
HP:0000470	Short neck
HP:0000582	Upslanted palpebral fissure
HP:0000952	Jaundice
HP:0000998	Hypertrichosis
HP:0001167	Abnormal finger morphology
HP:0001181	Adducted thumb
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001272	Cerebellar atrophy
HP:0001284	Areflexia
HP:0001290	Generalized hypotonia
HP:0001410	Decreased liver function
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation
HP:0001518	Small for gestational age
HP:0001522	Death in infancy
HP:0001627	Abnormal heart morphology
HP:0001635	Congestive heart failure
HP:0001684	Secundum atrial septal defect
HP:0001744	Splenomegaly
HP:0001943	Hypoglycemia
HP:0001954	Recurrent fever
HP:0001999	Abnormal facial shape
HP:0002014	Diarrhea
HP:0002020	Gastroesophageal reflux
HP:0002059	Cerebral atrophy
HP:0002079	Hypoplasia of the corpus callosum
HP:0002093	Respiratory insufficiency
HP:0002240	Hepatomegaly
HP:0002719	Recurrent infections
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003186	Inverted nipples
HP:0003196	Short nose
HP:0003202	Skeletal muscle atrophy
HP:0003236	Elevated circulating creatine kinase activity
HP:0003577	Congenital onset
HP:0004322	Short stature
HP:0004425	Flat forehead
HP:0007392	Excessive wrinkled skin
HP:0008897	Postnatal growth retardation
HP:0010557	Overlapping fingers
HP:0010808	Protruding tongue
HP:0011451	Primary microcephaly

GWAS associations

1 associations:

Study	Trait	p-value
GCST002789_3	Egg allergy	4e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0007018	egg allergy measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C535754	Congenital disorder of glycosylation type 2E *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105843 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

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

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.75	Kd	17.96	nM	CHEMBL3752910
7.75	ED50	17.96	nM	CHEMBL3752910
5.43	Kd	3709	nM	CHEMBL5653589
5.43	ED50	3709	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 6 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148109: Binding affinity to human COG7 incubated for 45 mins by Kinobead based pull down assay	kd	0.0180	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148109: Binding affinity to human COG7 incubated for 45 mins by Kinobead based pull down assay	kd	3.7088	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, increases expression, affects cotreatment, affects expression (+1 more)	4
Acetaminophen	decreases expression	3
Valproic Acid	decreases expression, increases expression	2
ginger extract	affects cotreatment, affects expression, increases abundance	1
2,4,6-tribromophenol	decreases expression	1
uranyl acetate	affects expression	1
decabromobiphenyl ether	increases expression	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Oils, Volatile	affects cotreatment, affects expression, increases abundance	1
Phthalic Acids	decreases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Selenium	increases expression	1
Uranium	affects expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Lactic Acid	decreases 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
CHEMBL4012605	Binding	Binding affinity to COG7 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 COG7 across ~30M SureChEMBL compounds — explore on Sugi Predict.