COG5

Summary

COG5 (component of oligomeric golgi complex 5, HGNC:14857) is a protein-coding gene on chromosome 7q22.3, encoding Conserved oligomeric Golgi complex subunit 5 (Q9UP83). Required for normal Golgi function. It is a selective cancer dependency (DepMap: 10.6% of cell lines).

The protein encoded by this gene is one of eight proteins (Cog1-8) which form a Golgi-localized complex (COG) required for normal Golgi morphology and function. The encoded protein is organized with conserved oligomeric Golgi complex components 6, 7 and 8 into a sub-complex referred to as lobe B. Alternative splicing results in multiple transcript variants. Mutations in this gene result in congenital disorder of glycosylation type 2I.

Source: NCBI Gene 10466 — RefSeq curated summary.

At a glance

• Gene–disease (curated): COG5-congenital disorder of glycosylation (Definitive, ClinGen)
• GWAS associations: 18
• Clinical variants (ClinVar): 1,023 total — 53 pathogenic, 23 likely-pathogenic
• Phenotypes (HPO): 52
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 10.6% of screened cell lines
• MANE Select transcript: NM_006348

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14857
Approved symbol	COG5
Name	component of oligomeric golgi complex 5
Location	7q22.3
Locus type	gene with protein product
Status	Approved
Aliases	GTC90
Ensembl gene	ENSG00000164597
Ensembl biotype	protein_coding
OMIM	606821
Entrez	10466

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000297135, ENST00000347053, ENST00000393603, ENST00000462342, ENST00000464542, ENST00000468350, ENST00000469503, ENST00000475638, ENST00000484237, ENST00000605888, ENST00000889949

RefSeq mRNA: 9 — MANE Select: NM_006348 NM_001161520, NM_001379511, NM_001379512, NM_001379513, NM_001379514, NM_001379515, NM_001379516, NM_006348, NM_181733

CCDS: CCDS55152, CCDS5742, CCDS5743

Canonical transcript exons

ENST00000297135 — 22 exons

Exon	Start	End
ENSE00001085736	107210526	107210605
ENSE00001085737	107283571	107283732
ENSE00001085747	107281300	107281399
ENSE00001085749	107362033	107362110
ENSE00001085751	107298142	107298346
ENSE00001174037	107201372	107203630
ENSE00001258643	107324440	107324521
ENSE00001815958	107563803	107563920
ENSE00003344475	107557976	107558115
ENSE00003356223	107554285	107554342
ENSE00003493572	107548278	107548332
ENSE00003501369	107372595	107372760
ENSE00003502073	107211099	107211225
ENSE00003575754	107362308	107362420
ENSE00003589265	107230615	107230691
ENSE00003607225	107548111	107548180
ENSE00003633135	107412502	107412632
ENSE00003635901	107236450	107236687
ENSE00003666129	107256732	107256794
ENSE00003669980	107248396	107248499
ENSE00003681028	107258273	107258383
ENSE00003785861	107527237	107527357

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 96.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.6929 / max 315.5645, expressed in 1821 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85603	36.7884	1821
85605	0.6415	363
85604	0.2563	101
85602	0.0068	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	96.80	gold quality
calcaneal tendon	UBERON:0003701	95.80	gold quality
tonsil	UBERON:0002372	93.38	gold quality
bone marrow cell	CL:0002092	92.89	gold quality
sural nerve	UBERON:0015488	92.73	gold quality
colonic epithelium	UBERON:0000397	92.07	gold quality
skeletal muscle tissue	UBERON:0001134	90.98	gold quality
bone marrow	UBERON:0002371	90.82	gold quality
bone element	UBERON:0001474	90.81	gold quality
adrenal tissue	UBERON:0018303	90.72	gold quality
muscle tissue	UBERON:0002385	90.50	gold quality
endometrium	UBERON:0001295	90.47	gold quality
smooth muscle tissue	UBERON:0001135	90.18	gold quality
right atrium auricular region	UBERON:0006631	89.71	gold quality
uterine cervix	UBERON:0000002	89.20	gold quality
heart	UBERON:0000948	88.81	gold quality
heart left ventricle	UBERON:0002084	88.67	gold quality
rectum	UBERON:0001052	88.66	gold quality
cortical plate	UBERON:0005343	88.66	gold quality
monocyte	CL:0000576	88.53	gold quality
uterus	UBERON:0000995	88.39	gold quality
leukocyte	CL:0000738	88.34	gold quality
islet of Langerhans	UBERON:0000006	88.26	gold quality
stromal cell of endometrium	CL:0002255	88.16	gold quality
ventricular zone	UBERON:0003053	88.12	gold quality
pancreas	UBERON:0001264	87.80	gold quality
endocervix	UBERON:0000458	87.77	gold quality
ectocervix	UBERON:0012249	87.26	gold quality
body of pancreas	UBERON:0001150	87.17	gold quality
urinary bladder	UBERON:0001255	87.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	18.37
E-ANND-3	no	2.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR2

miRNA regulators (miRDB)

99 targeting COG5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-1299	99.77	71.24	2389

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• Sec34 is implicated in traffic from the endoplasmic reticulum to the Golgi and exists in a complex with GTC-90 and ldlBp (PMID:11929878)
• COG5- and COG7 subunits play distinctive roles in controlling Golgi structure and function (PMID:16051600)
• Report on a uterine leiomyoma with a novel HMGA2 fusion gene in a 44-year-old woman. (PMID:20804914)
• In conclusion, we find that GDF5, but not COG5 or MCF2L, influence the extent of radiographic damage in knee osteoarthritis (PMID:22615457)
• 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)
• Fetal glycosylation defect due to ALG3 and COG5 variants detected via amniocentesis: Complex glycosylation defect with embryonic lethal phenotype. (PMID:33187827)
• COG5 variants lead to complex early onset retinal degeneration, upregulation of PERK and DNA damage. (PMID:33277529)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cog5	ENSDARG00000008235
mus_musculus	Cog5	ENSMUSG00000035933
rattus_norvegicus	Cog5	ENSRNOG00000056610
drosophila_melanogaster	fws	FBGN0024689
caenorhabditis_elegans	cogc-5	WBGENE00016608

Protein

Protein identifiers

Conserved oligomeric Golgi complex subunit 5 — Q9UP83 (reviewed: Q9UP83)

Alternative names: 13S Golgi transport complex 90 kDa subunit, Component of oligomeric Golgi complex 5, Golgi transport complex 1

All UniProt accessions (4): A0AAA9X096, A0AAA9X2X8, Q9UP83, U3KQU7

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. Cytoplasm. Cytosol. Golgi apparatus membrane.

Disease relevance. Congenital disorder of glycosylation 2I (CDG2I) [MIM:613612] 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. Congenital disorder of glycosylation type 2I is characterized by mild neurological impairments. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the COG5 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UP83-2	1	yes
Q9UP83-1	4
Q9UP83-3	3
Q9UP83-4	2

RefSeq proteins (9): NP_001154992, NP_001366440, NP_001366441, NP_001366442, NP_001366443, NP_001366444, NP_001366445, NP_006339, NP_859422 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019465	Cog5	Family
IPR048485	COG5_helical	Domain
IPR049176	COG5_N	Domain

Pfam: PF10392, PF20649

UniProt features (11 total): sequence variant 4, splice variant 3, chain 1, region of interest 1, sequence conflict 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UP83-F1	84.37	0.64

Functional residue map

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

Post-translational modifications (1): 197

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811438	Intra-Golgi traffic
R-HSA-6811440	Retrograde transport at the Trans-Golgi-Network

MSigDB gene sets: 274 (showing top): GCM_GSPT1, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_INTRA_GOLGI_VESICLE_MEDIATED_TRANSPORT, GOCC_TRANS_GOLGI_NETWORK, WANG_LMO4_TARGETS_DN, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, DOUGLAS_BMI1_TARGETS_DN, AACTTT_UNKNOWN, DING_LUNG_CANCER_EXPRESSION_BY_COPY_NUMBER, GCM_NF2, MODULE_204, GOBP_GOLGI_ORGANIZATION, GOCC_GOLGI_TRANSPORT_COMPLEX, BENPORATH_MYC_MAX_TARGETS

GO Biological Process (6): retrograde transport, vesicle recycling within Golgi (GO:0000301), intra-Golgi vesicle-mediated transport (GO:0006891), Golgi organization (GO:0007030), protein transport (GO:0015031), inter-Golgi cisterna vesicle-mediated transport (GO:0048219), obsolete glycosylation (GO:0070085)

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

GO Cellular Component (8): Golgi membrane (GO:0000139), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), cytosol (GO:0005829), membrane (GO:0016020), COG complex (GO:0017119), trans-Golgi network membrane (GO:0032588), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Intra-Golgi and retrograde Golgi-to-ER traffic	2
ER to Golgi Anterograde Transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intra-Golgi vesicle-mediated transport	2
Golgi apparatus	2
cytoplasm	2
Golgi vesicle transport	1
organelle organization	1
endomembrane system organization	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
binding	1
bounding membrane of organelle	1
nuclear lumen	1
endomembrane system	1
intracellular membrane-bounded organelle	1
vesicle tethering complex	1
trans-Golgi network	1
organelle membrane	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1046 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COG5	COG7	P83436	998
COG5	COG2	Q14746	996
COG5	COG1	Q8WTW3	996
COG5	COG3	Q96JB2	991
COG5	COG8	Q96MW5	991
COG5	COG6	Q9Y2V7	979
COG5	COG4	Q9H9E3	978
COG5	COPB1	P53618	797
COG5	STX5	Q13190	717
COG5	DUS4L	O95620	714
COG5	GPR22	Q99680	699
COG5	GOSR2	O14653	693
COG5	VPS53	Q5VIR6	688
COG5	GOLGA5	Q8TBA6	668
COG5	TGOLN2	O43493	633
COG5	BCAP29	Q9UHQ4	633

IntAct

72 interactions, top by confidence:

A	B	Type	Score
ODAD1	HGS	psi-mi:“MI:0914”(association)	0.850
COG7	ILVBL	psi-mi:“MI:0914”(association)	0.640
COMMD8	VPS26C	psi-mi:“MI:0914”(association)	0.640
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
COG5	COG4	psi-mi:“MI:0915”(physical association)	0.560
COG4	COG5	psi-mi:“MI:0915”(physical association)	0.560
COG7	COG5	psi-mi:“MI:0915”(physical association)	0.560
COG5	COG7	psi-mi:“MI:0915”(physical association)	0.560
COG5	BSG	psi-mi:“MI:0914”(association)	0.530
ILVBL	SLC33A1	psi-mi:“MI:0914”(association)	0.530
CD40	EXOC5	psi-mi:“MI:0914”(association)	0.530
COG2	COG7	psi-mi:“MI:0914”(association)	0.530
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
BSG	BTAF1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
STX3	NBAS	psi-mi:“MI:0914”(association)	0.530
Traf5	COG7	psi-mi:“MI:0914”(association)	0.500
POC1A	TXNDC9	psi-mi:“MI:0914”(association)	0.480
Poc1b		psi-mi:“MI:0915”(physical association)	0.400
Nek9	AURKA	psi-mi:“MI:0915”(physical association)	0.400
FOXB1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXL1	DDX39A	psi-mi:“MI:0914”(association)	0.350
CDKN1A	CCNE1	psi-mi:“MI:0914”(association)	0.350
SLC25A28	DNAJB6	psi-mi:“MI:0914”(association)	0.350
UNC93B1		psi-mi:“MI:0914”(association)	0.350
P2RY6	RAVER1	psi-mi:“MI:0914”(association)	0.350
	NBAS	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350

BioGRID (128): COG5 (Affinity Capture-MS), COG5 (Affinity Capture-MS), COG5 (Affinity Capture-MS), COG5 (Affinity Capture-MS), COG5 (Affinity Capture-MS), COG5 (Affinity Capture-MS), COG5 (Affinity Capture-MS), COG1 (Co-fractionation), COG2 (Co-fractionation), COG3 (Co-fractionation), COG4 (Co-fractionation), COG6 (Co-fractionation), COG7 (Co-fractionation), STK24 (Co-fractionation), COG5 (Affinity Capture-MS)

ESM2 similar proteins: A1C7E5, A1CU89, A1DNX2, A2QCV0, A2QLL1, A4QUK5, A6R6L9, A6SG03, A7EM16, A7ERK2, A7KAM6, B2WB15, C8V7C6, E3RYW5, E4ZUJ1, G0S4F3, I1RR07, P0CM80, P0CM81, P0CN62, P0CN63, P0CR64, P0CR65, Q0CSR3, Q0CY33, Q0UYL3, Q1DQB2, Q1E6R9, Q29N70, Q2HH52, Q2UFN7, Q2UUV3, Q4ILI9, Q4WHU0, Q4WLS7, Q4WM32, Q4X0B0, Q4X0X6, Q524Z5, Q5AZC0

Diamond homologs: Q8C0L8, Q9C9V9, Q9UP83

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
COG5	“form complex”	“COG tethering complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

1023 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	53
Likely pathogenic	23
Uncertain significance	449
Likely benign	342
Benign	79

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1030100	NM_006348.5(COG5):c.847C>T (p.Arg283Ter)	Pathogenic
1366509	NM_006348.5(COG5):c.1791_1794del (p.Thr598fs)	Pathogenic
1370025	NM_006348.5(COG5):c.729_730dup (p.Thr244fs)	Pathogenic
1385615	NM_006348.5(COG5):c.2234dup (p.Ser746fs)	Pathogenic
1394561	NM_006348.5(COG5):c.1179G>A (p.Trp393Ter)	Pathogenic
1399862	NM_006348.5(COG5):c.961C>T (p.Gln321Ter)	Pathogenic
1412792	NM_006348.5(COG5):c.2167del (p.Arg723fs)	Pathogenic
1419371	NC_000007.13:g.(?107052927)(107053097_?)del	Pathogenic
1423715	NM_006348.5(COG5):c.1627C>T (p.Gln543Ter)	Pathogenic
1444263	NM_006348.5(COG5):c.2263A>T (p.Arg755Ter)	Pathogenic
1450443	NC_000007.13:g.(?106897157)(107002885_?)del	Pathogenic
1456195	NC_000007.13:g.(?106897157)(106938811_?)del	Pathogenic
1457759	NM_006348.5(COG5):c.613C>T (p.Arg205Ter)	Pathogenic
1458630	NC_000007.13:g.(?107167662)(107167822_?)del	Pathogenic
1458631	NC_000007.13:g.(?107002458)(107053097_?)del	Pathogenic
1459555	NC_000007.13:g.(?107002458)(107002885_?)del	Pathogenic
1460265	NC_000007.13:g.(?107002458)(107204434_?)del	Pathogenic
1960598	NM_006348.5(COG5):c.697del (p.Gln233fs)	Pathogenic
1979585	NM_006348.5(COG5):c.811C>T (p.Gln271Ter)	Pathogenic
1992216	NM_006348.5(COG5):c.652C>T (p.Gln218Ter)	Pathogenic
2010221	NM_006348.5(COG5):c.1179del (p.Leu392_Trp393insTer)	Pathogenic
2014849	NM_006348.5(COG5):c.1410dup (p.Pro471fs)	Pathogenic
2019978	NM_006348.5(COG5):c.936del (p.Val313fs)	Pathogenic
2034545	NM_006348.5(COG5):c.832A>T (p.Arg278Ter)	Pathogenic
2086480	NM_006348.5(COG5):c.1248T>G (p.Tyr416Ter)	Pathogenic
2104290	NM_006348.5(COG5):c.1570C>T (p.Gln524Ter)	Pathogenic
2159643	NM_006348.5(COG5):c.1015G>T (p.Glu339Ter)	Pathogenic
2425576	NC_000007.13:g.(?106964865)(106964986_?)del	Pathogenic
2425577	NC_000007.13:g.(?107188536)(107204434_?)del	Pathogenic
2425578	NC_000007.13:g.(?106921725)(106924197_?)del	Pathogenic

SpliceAI

4707 predictions. Top by Δscore:

Variant	Effect	Δscore
7:107248391:ATTAC:A	donor_loss	1.0000
7:107248392:TTA:T	donor_loss	1.0000
7:107248393:TAC:T	donor_loss	1.0000
7:107248394:A:AC	donor_gain	1.0000
7:107248394:A:C	donor_loss	1.0000
7:107248394:AC:A	donor_gain	1.0000
7:107248395:C:A	donor_loss	1.0000
7:107248395:C:CC	donor_gain	1.0000
7:107248395:CC:C	donor_gain	1.0000
7:107248495:ATAGC:A	acceptor_gain	1.0000
7:107248496:TAGC:T	acceptor_gain	1.0000
7:107248497:AGC:A	acceptor_gain	1.0000
7:107248497:AGCCT:A	acceptor_loss	1.0000
7:107248498:GC:G	acceptor_gain	1.0000
7:107248498:GCCT:G	acceptor_loss	1.0000
7:107248499:CC:C	acceptor_gain	1.0000
7:107248499:CCTA:C	acceptor_loss	1.0000
7:107248500:C:CC	acceptor_gain	1.0000
7:107248500:C:CG	acceptor_loss	1.0000
7:107248501:T:A	acceptor_loss	1.0000
7:107281298:A:AC	donor_gain	1.0000
7:107281299:C:CC	donor_gain	1.0000
7:107281299:CAA:C	donor_gain	1.0000
7:107281299:CAAG:C	donor_gain	1.0000
7:107281395:GTTCA:G	acceptor_gain	1.0000
7:107281396:TTCA:T	acceptor_gain	1.0000
7:107281397:TCA:T	acceptor_gain	1.0000
7:107281398:CA:C	acceptor_gain	1.0000
7:107281398:CAC:C	acceptor_gain	1.0000
7:107281399:AC:A	acceptor_loss	1.0000

AlphaMissense

5606 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:107236631:A:G	L647P	0.999
7:107210572:A:G	W787R	0.998
7:107210572:A:T	W787R	0.998
7:107236469:A:G	L701P	0.998
7:107283661:A:G	L493P	0.998
7:107527257:G:T	A204D	0.998
7:107236461:C:G	D704H	0.997
7:107283664:C:G	R492P	0.997
7:107372735:A:G	L263P	0.997
7:107527302:A:G	L189P	0.997
7:107548115:A:G	L169P	0.997
7:107548124:A:G	L166P	0.997
7:107203566:A:C	Y824D	0.996
7:107210570:C:A	W787C	0.996
7:107210570:C:G	W787C	0.996
7:107210596:A:G	W779R	0.996
7:107210596:A:T	W779R	0.996
7:107236644:A:C	Y643D	0.996
7:107258321:A:C	N577K	0.996
7:107258321:A:T	N577K	0.996
7:107283686:A:C	Y485D	0.996
7:107527239:A:G	L210P	0.996
7:107527248:A:G	L207P	0.996
7:107554309:C:G	A121P	0.996
7:107203622:A:G	L805P	0.995
7:107211156:G:C	S756R	0.995
7:107211156:G:T	S756R	0.995
7:107211158:T:G	S756R	0.995
7:107236461:C:A	D704Y	0.995
7:107236507:A:C	S688R	0.995

dbSNP variants (sampled 300 via entrez): RS1000004212 (7:107407163 T>A,C), RS1000034860 (7:107533537 G>A,T), RS1000038820 (7:107201574 AATAAT>A,AATAATATAAT), RS1000041181 (7:107308197 T>G), RS1000061335 (7:107406906 G>A,T), RS1000063549 (7:107287095 T>C), RS1000066034 (7:107307273 C>T), RS1000078538 (7:107424192 G>A), RS1000085222 (7:107533313 A>C), RS1000091198 (7:107556706 T>C), RS1000101918 (7:107226349 A>C), RS1000112112 (7:107266522 T>C), RS1000113938 (7:107413358 G>A,C), RS1000117774 (7:107290415 T>C), RS1000126125 (7:107508664 T>C)

Disease associations

OMIM: gene MIM:606821 | disease phenotypes: MIM:613612, MIM:123100

GenCC curated gene-disease

Disease	Classification	Inheritance
COG5-congenital disorder of glycosylation	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
COG5-congenital disorder of glycosylation	Definitive	AR

Mondo (2): COG5-congenital disorder of glycosylation (MONDO:0013325), craniosynostosis (MONDO:0015469)

Orphanet (2): COG5-CDG (Orphanet:263487), Craniosynostosis (Orphanet:1531)

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000020	Urinary incontinence
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000448	Prominent nose
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000599	Abnormality of the frontal hairline
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001348	Brisk reflexes
HP:0001433	Hepatosplenomegaly
HP:0001511	Intrauterine growth retardation
HP:0001562	Oligohydramnios
HP:0002059	Cerebral atrophy

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000558_1	Osteoarthritis	8.000000e-08
GCST005956_26	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST005962_48	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-06
GCST006061_100	Atrial fibrillation	5.000000e-09
GCST006612_112	LDL cholesterol	8.000000e-09
GCST006629_63	Pulse pressure	5.000000e-11
GCST006976_53	Macular thickness	2.000000e-10
GCST007269_274	Pulse pressure	8.000000e-09
GCST007927_25	Medication use (beta blocking agents)	2.000000e-08
GCST009391_1163	Metabolite levels	4.000000e-06
GCST010241_29	Apolipoprotein A1 levels	6.000000e-17
GCST010242_318	HDL cholesterol levels	8.000000e-14
GCST010796_4293	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-12
GCST010796_4294	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-12
GCST011353_46	Serum alkaline phosphatase levels	3.000000e-08
GCST011494_38	Daytime nap	2.000000e-12
GCST90002394_309	Monocyte percentage of white cells	2.000000e-10
GCST90011900_191	Serum alkaline phosphatase levels	4.000000e-20

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0005763	pulse pressure measurement
EFO:0009929	Beta blocking agent use measurement
EFO:0010460	anthranilic acid measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004327	electrocardiography
EFO:0004533	alkaline phosphatase measurement
EFO:0007828	daytime rest measurement
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067280 (SINGLE PROTEIN)

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

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
5.14	Kd	7288	nM	CHEMBL3752910
5.14	ED50	7288	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	2148107: Binding affinity to human COG5 incubated for 45 mins by Kinobead based pull down assay	kd	7.2878	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	5
Valproic Acid	increases expression, decreases expression, affects cotreatment	4
sodium arsenite	affects binding, increases reaction, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	increases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
ICG 001	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	decreases expression	1
Coumestrol	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression	1
Phthalic Acids	decreases methylation	1
Potassium Dichromate	decreases expression	1
Quercetin	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
CHEMBL5651149	Binding	Binding affinity to human COG5 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)

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

Trial	Phase	Status	Title
NCT00722436	PHASE4	TERMINATED	Tranexamic Acid for Craniofacial Surgery
NCT02188576	PHASE4	COMPLETED	The Efficacy and Population Pharmacokinetics of Tranexamic Acid for Craniosynostosis Surgery
NCT02229968	PHASE2	ACTIVE_NOT_RECRUITING	Efficacy of Amicar for Children Having Craniofacial Surgery
NCT00912119	PHASE1	COMPLETED	Amicar Pharmacokinetics of Children Having Craniofacial Surgery
NCT00077831	Not specified	COMPLETED	Child and Infant Learning Project
NCT00106977	Not specified	COMPLETED	Clinical Study of Muenke Syndrome (FGFR3-Related Craniosynostosis)
NCT00367796	Not specified	COMPLETED	Genetic Analysis of Craniosynostosis, Philadelphia Type
NCT00769847	Not specified	WITHDRAWN	Endoscopic Treatment for Isolated, Single Suture Craniosynostosis
NCT00773643	Not specified	COMPLETED	Osteogenic Profiling of Tissue From Children With Craniosynostosis
NCT01898650	Not specified	COMPLETED	MRI for Non-invasive Evaluation of Brain Stress
NCT02287805	Not specified	COMPLETED	Qualitative and Quantitative Study Which Aims to Determine the Specifics of the Announcement for the Diagnosis of Patients With Craniosynostosis and Their Parents to Better Support Them in Their Care
NCT02561728	Not specified	WITHDRAWN	Hanger Helmet Study
NCT03025763	Not specified	ACTIVE_NOT_RECRUITING	Network Of Clinical Research Studies On Craniosynostosis, Skull Malformations With Premature Fusion Of Skull Bones
NCT03231085	Not specified	COMPLETED	Comparison of the Rate of Preoperative Haemoglobin After Administration of Epoetin Alpha Associated With an Oral Medical Supplementation Versus Intravenous Before Surgery of Craniosynostosis at the Child
NCT04704284	Not specified	COMPLETED	Comparing MRI to CT on Pediatric Craniosynostosis.
NCT05911139	Not specified	ENROLLING_BY_INVITATION	Influence of General Anesthesia on the Dynamic Changes in Brain Damage Markers During and After Craniosynostosis Operations in Infancy
NCT06928727	Not specified	RECRUITING	Ocular Characteristics in Patients With Craniosynostosis