COG8

Summary

COG8 (component of oligomeric golgi complex 8, HGNC:18623) is a protein-coding gene on chromosome 16q22.1, encoding Conserved oligomeric Golgi complex subunit 8 (Q96MW5). Required for normal Golgi function. It is a selective cancer dependency (DepMap: 63.0% of cell lines).

This gene encodes a protein that is a component of the conserved oligomeric Golgi (COG) complex, a multiprotein complex that plays a structural role in the Golgi apparatus, and is involved in intracellular membrane trafficking and glycoprotein modification. Mutations in this gene cause congenital disorder of glycosylation, type IIh, a disease that is characterized by under-glycosylated serum proteins, and whose symptoms include severe psychomotor retardation, failure to thrive, seizures, and dairy and wheat product intolerance.

Source: NCBI Gene 84342 — RefSeq curated summary.

At a glance

• Gene–disease (curated): COG8-congenital disorder of glycosylation (Definitive, ClinGen)
• GWAS associations: 3
• Clinical variants (ClinVar): 340 total — 5 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 76
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 63.0% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_032382

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18623
Approved symbol	COG8
Name	component of oligomeric golgi complex 8
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22315, DOR1
Ensembl gene	ENSG00000213380
Ensembl biotype	protein_coding
OMIM	606979
Entrez	84342

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000306875, ENST00000562081, ENST00000562595, ENST00000564419, ENST00000567493, ENST00000615447

RefSeq mRNA: 8 — MANE Select: NM_032382 NM_001374871, NM_001379261, NM_001379262, NM_001379263, NM_001379264, NM_001379265, NM_001379266, NM_032382

CCDS: CCDS10876, CCDS92189

Canonical transcript exons

ENST00000306875 — 6 exons

Exon	Start	End
ENSE00001141276	69330813	69331095
ENSE00001141321	69332714	69332882
ENSE00001610740	69326428	69329179
ENSE00003838611	69336505	69336712
ENSE00003839008	69339176	69339564
ENSE00003840902	69334521	69335348

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 89.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.4364 / max 100.8374, expressed in 1807 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157900	24.3131	1806
157898	0.0616	8
157901	0.0377	4
157899	0.0240	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	89.50	silver quality
kidney epithelium	UBERON:0004819	88.43	silver quality
tibialis anterior	UBERON:0001385	88.23	silver quality
stromal cell of endometrium	CL:0002255	87.32	gold quality
gastrocnemius	UBERON:0001388	87.10	gold quality
muscle of leg	UBERON:0001383	86.88	gold quality
ileal mucosa	UBERON:0000331	86.65	gold quality
right adrenal gland	UBERON:0001233	86.51	gold quality
cerebellar vermis	UBERON:0004720	86.29	silver quality
right adrenal gland cortex	UBERON:0035827	86.17	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.13	gold quality
left adrenal gland	UBERON:0001234	85.53	gold quality
ventricular zone	UBERON:0003053	85.10	gold quality
left adrenal gland cortex	UBERON:0035825	84.92	gold quality
adrenal cortex	UBERON:0001235	84.78	gold quality
adrenal tissue	UBERON:0018303	84.50	gold quality
deltoid	UBERON:0001476	84.29	silver quality
cortex of kidney	UBERON:0001225	84.28	gold quality
mucosa of transverse colon	UBERON:0004991	84.24	gold quality
adrenal gland	UBERON:0002369	84.23	gold quality
left testis	UBERON:0004533	84.23	gold quality
right lobe of liver	UBERON:0001114	84.18	gold quality
skeletal muscle tissue	UBERON:0001134	84.15	gold quality
muscle tissue	UBERON:0002385	84.00	gold quality
ganglionic eminence	UBERON:0004023	83.98	gold quality
right testis	UBERON:0004534	83.98	gold quality
left ventricle myocardium	UBERON:0006566	83.92	gold quality
islet of Langerhans	UBERON:0000006	83.87	gold quality
granulocyte	CL:0000094	83.78	gold quality
body of pancreas	UBERON:0001150	83.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting COG8, 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-4267	99.96	66.53	2368
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-934	98.49	70.44	581
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-30C-1-3P	97.80	66.36	1499
HSA-MIR-30C-2-3P	97.80	66.45	1499
HSA-MIR-6788-5P	97.80	66.41	1532
HSA-MIR-3127-5P	97.52	65.24	786
HSA-MIR-509-3-5P	97.21	67.74	1517
HSA-MIR-509-5P	97.21	67.90	1512
HSA-MIR-4418	97.04	67.16	1372
HSA-MIR-212-5P	96.83	67.43	950
HSA-MIR-1287-5P	96.80	65.30	743
HSA-MIR-4652-5P	96.46	64.22	553
HSA-MIR-1258	96.08	67.74	700

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 63.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• wthe origin, evolution and preservation of the COG8/PDF same-strand overlap follow similar mechanistic steps as those documented for antisense overlaps where gain and/or loss of splice sites and polyadenylation signals seems to drive the process. (PMID:21805148)
• Targeted silencing of components of lobe B of the COG complex, namely COG5, COG6, COG7 and COG8, inhibited HIV-1 replication (PMID:25179963)
• TMED6-COG8 chimera might act as a novel diagnostic marker in TFE3 translocation renal cell carcinoma. (PMID:26045774)
• The exome sequencing was performed to screen all CDG type II-related genes, and two novel frameshift mutations were found: c.171dupG (p.Leu58Alafs*29) and c.1656dupC (p.Ala553Argfs*15) in COG8. (PMID:28619360)
• TMEM-COG4, COG7 and COG8 subunits restore endogenous COG localization to the Golgi membranes (PMID:29467253)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cog8	ENSDARG00000002798
mus_musculus	Cog8	ENSMUSG00000031916
rattus_norvegicus	Cog8	ENSRNOG00000020379
drosophila_melanogaster	Cog8	FBGN0287204
caenorhabditis_elegans		WBGENE00019820

Protein

Protein identifiers

Conserved oligomeric Golgi complex subunit 8 — Q96MW5 (reviewed: Q96MW5)

Alternative names: Component of oligomeric Golgi complex 8

All UniProt accessions (6): A0A087X1T3, B4DYU2, H3BQV3, H3BSH5, J3QRV3, Q96MW5

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 2H (CDG2H) [MIM:611182] CDGs are a family of severe inherited diseases caused by a defect in protein N-glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of 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 COG8 family.

RefSeq proteins (8): NP_001361800, NP_001366190, NP_001366191, NP_001366192, NP_001366193, NP_001366194, NP_001366195, NP_115758* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007255	COG8	Family
IPR016159	Cullin_repeat-like_dom_sf	Homologous_superfamily
IPR016632	COG8_Metazoal_Plant	Family

Pfam: PF04124

UniProt features (5 total): sequence conflict 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96MW5-F1	80.67	0.56

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: 271 (showing top): chr16q22, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_INTRA_GOLGI_VESICLE_MEDIATED_TRANSPORT, GOCC_TRANS_GOLGI_NETWORK, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_GOLGI_ORGANIZATION, GOCC_GOLGI_TRANSPORT_COMPLEX, GOCC_TRANS_GOLGI_NETWORK_MEMBRANE, GOCC_ORGANELLE_SUBCOMPARTMENT, GOBP_GOLGI_VESICLE_TRANSPORT, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, PURBEY_TARGETS_OF_CTBP1_AND_SATB1_UP, GOCC_VESICLE_TETHERING_COMPLEX, REACTOME_ER_TO_GOLGI_ANTEROGRADE_TRANSPORT

GO Biological Process (5): retrograde transport, vesicle recycling within Golgi (GO:0000301), intra-Golgi vesicle-mediated transport (GO:0006891), Golgi organization (GO:0007030), protein transport (GO:0015031), obsolete glycosylation (GO:0070085)

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

GO Cellular Component (5): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), membrane (GO:0016020), COG complex (GO:0017119), trans-Golgi network membrane (GO:0032588)

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

Protein interactions and networks

STRING

1146 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COG8	COG1	Q8WTW3	996
COG8	COG5	Q9UP83	991
COG8	COG6	Q9Y2V7	990
COG8	COG3	Q96JB2	986
COG8	COG2	Q14746	986
COG8	COG7	P83436	985
COG8	COG4	Q9H9E3	980
COG8	STX5	Q13190	819
COG8	STX16	O14662	819
COG8	GOSR2	O14653	798
COG8	RIC1	Q4ADV7	745
COG8	EXOC2	Q96KP1	730
COG8	STX6	O43752	713
COG8	VPS53	Q5VIR6	713
COG8	GOLGA5	Q8TBA6	709

IntAct

119 interactions, top by confidence:

A	B	Type	Score
COG4	COG7	psi-mi:“MI:0914”(association)	0.670
COMMD8	VPS26C	psi-mi:“MI:0914”(association)	0.640
COG3	COG7	psi-mi:“MI:0914”(association)	0.640
COG7	ILVBL	psi-mi:“MI:0914”(association)	0.640
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
GEM	COG8	psi-mi:“MI:0915”(physical association)	0.560
COG8	MYEF2	psi-mi:“MI:0915”(physical association)	0.560
COG8	GEM	psi-mi:“MI:0915”(physical association)	0.560
HGS	COG8	psi-mi:“MI:0915”(physical association)	0.560
COG8		psi-mi:“MI:0915”(physical association)	0.560
NDUFS1	COG8	psi-mi:“MI:0915”(physical association)	0.560
COG8	TTR	psi-mi:“MI:0915”(physical association)	0.560
BAG6	COG8	psi-mi:“MI:0915”(physical association)	0.560
KLF11	COG8	psi-mi:“MI:0915”(physical association)	0.560
NUP58	COG8	psi-mi:“MI:0915”(physical association)	0.560
COG8	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
HTT	COG8	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (94): COG8 (Two-hybrid), COG8 (Two-hybrid), COG8 (Affinity Capture-MS), COG8 (Affinity Capture-MS), COG8 (Affinity Capture-MS), COG8 (Affinity Capture-MS), COG1 (Co-fractionation), COG4 (Co-fractionation), COG8 (Co-fractionation), COG8 (Co-fractionation), COG8 (Synthetic Lethality), COG8 (Synthetic Lethality), COG8 (Affinity Capture-MS), COG8 (Affinity Capture-MS), COG8 (Affinity Capture-MS)

ESM2 similar proteins: A2AV37, A2BID5, A2VDR8, A7E2Y6, A7Z033, B4DZS4, O15068, O35821, O60645, O70576, O94812, P52630, P83436, Q01755, Q03169, Q08CY4, Q0P4Q0, Q0V8C2, Q14746, Q15021, Q17RC7, Q19262, Q1LXZ7, Q2TBH9, Q3T1G7, Q3TBD2, Q3UM29, Q5H9J9, Q5XI00, Q61333, Q62825, Q63406, Q64096, Q6DIA2, Q6GPP1, Q6KAR6, Q7T006, Q80TT2, Q80VA5, Q8K1H7

Diamond homologs: Q2TBH9, Q55BB8, Q84K25, Q96MW5, Q9JJA2, Q9VKH0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
COG8	“form complex”	“COG tethering complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Intra-Golgi traffic	7	35.6×	2e-07
Retrograde transport at the Trans-Golgi-Network	7	30.1×	3e-07
COPI-mediated anterograde transport	8	17.2×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
intra-Golgi vesicle-mediated transport	5	38.2×	2e-05
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	7	34.2×	3e-07
Golgi organization	9	17.4×	4e-07
protein transport	12	7.6×	6e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	9
Uncertain significance	194
Likely benign	78
Benign	15

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
1098271	NM_032382.5(COG8):c.1550_1556del (p.Leu517fs)	Pathogenic
1335988	NM_032382.5(COG8):c.1364_1371del (p.Val455fs)	Pathogenic
3647	NM_032382.5(COG8):c.1611C>G (p.Tyr537Ter)	Pathogenic
3648	NM_032382.5(COG8):c.1413+1G>A	Pathogenic
4712261	NM_032382.5(COG8):c.1027del (p.Asp343fs)	Pathogenic
1801207	NM_032382.5(COG8):c.1582+1G>A	Likely pathogenic
2504275	NM_032382.5(COG8):c.1396del (p.Glu466fs)	Likely pathogenic
2628993	NM_032382.5(COG8):c.547C>T (p.Arg183Ter)	Likely pathogenic
3767116	NM_032382.5(COG8):c.317_327dup (p.Ser110fs)	Likely pathogenic
3779115	NM_032382.5(COG8):c.513T>G (p.Tyr171Ter)	Likely pathogenic
3903164	NM_032382.5(COG8):c.1033_1034del (p.Leu345fs)	Likely pathogenic
391369	NM_032382.5(COG8):c.1580T>G (p.Leu527Ter)	Likely pathogenic
489229	NM_032382.5(COG8):c.973C>T (p.Gln325Ter)	Likely pathogenic
659501	NM_032382.5(COG8):c.585+1G>T	Likely pathogenic

SpliceAI

2069 predictions. Top by Δscore:

Variant	Effect	Δscore
16:69320140:G:GA	acceptor_gain	1.0000
16:69320140:G:GC	acceptor_gain	1.0000
16:69320140:GG:G	acceptor_gain	1.0000
16:69320140:GGC:G	acceptor_gain	1.0000
16:69320140:GGCT:G	acceptor_gain	1.0000
16:69320140:GGCTG:G	acceptor_gain	1.0000
16:69320239:A:T	donor_gain	1.0000
16:69320240:GA:G	donor_gain	1.0000
16:69320242:G:GG	donor_gain	1.0000
16:69320267:G:GT	donor_gain	1.0000
16:69320268:G:GT	donor_gain	1.0000
16:69320278:TCCAG:T	donor_gain	1.0000
16:69320285:GCAGG:G	donor_gain	1.0000
16:69320288:GG:G	donor_gain	1.0000
16:69320289:G:GT	donor_gain	1.0000
16:69320289:GGTG:G	donor_loss	1.0000
16:69320290:G:C	donor_loss	1.0000
16:69320682:CCACA:C	acceptor_loss	1.0000
16:69320683:CACA:C	acceptor_loss	1.0000
16:69320684:ACAG:A	acceptor_gain	1.0000
16:69320684:ACAGG:A	acceptor_gain	1.0000
16:69320685:CA:C	acceptor_loss	1.0000
16:69320686:A:AG	acceptor_gain	1.0000
16:69320686:AG:A	acceptor_gain	1.0000
16:69320686:AGG:A	acceptor_gain	1.0000
16:69320686:AGGG:A	acceptor_gain	1.0000
16:69320687:G:GG	acceptor_gain	1.0000
16:69320687:G:GT	acceptor_gain	1.0000
16:69320687:GG:G	acceptor_gain	1.0000
16:69320687:GGG:G	acceptor_gain	1.0000

AlphaMissense

4138 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:69336608:A:G	L161P	1.000
16:69336623:A:G	L156P	0.999
16:69339305:G:T	A83D	0.999
16:69336560:A:G	L177P	0.998
16:69336593:A:T	V166D	0.998
16:69339273:C:G	A94P	0.998
16:69339283:G:C	F90L	0.998
16:69339283:G:T	F90L	0.998
16:69339285:A:G	F90L	0.998
16:69336570:C:G	A174P	0.997
16:69336647:C:G	R148P	0.997
16:69336653:A:G	L146P	0.997
16:69336696:C:G	A132P	0.997
16:69339281:A:T	I91N	0.997
16:69339284:A:G	F90S	0.997
16:69339301:G:C	F84L	0.997
16:69339301:G:T	F84L	0.997
16:69339303:A:G	F84L	0.997
16:69335055:G:C	F293L	0.996
16:69335055:G:T	F293L	0.996
16:69335057:A:G	F293L	0.996
16:69335236:C:G	R233P	0.996
16:69336569:G:T	A174D	0.996
16:69336621:C:T	E157K	0.996
16:69336626:A:T	I155K	0.996
16:69336566:A:G	L175P	0.995
16:69336608:A:T	L161H	0.995
16:69336620:T:A	E157V	0.995
16:69339284:A:C	F90C	0.995
16:69335193:A:C	F247L	0.994

dbSNP variants (sampled 300 via entrez): RS1000102220 (16:69338897 G>A,T), RS1000159915 (16:69326488 T>G), RS1000204668 (16:69329766 G>A,C), RS1000354335 (16:69328587 A>G), RS1000422460 (16:69329415 G>A,C), RS1000451372 (16:69338637 C>A,G,T), RS1000788071 (16:69338162 A>T), RS1000840290 (16:69338374 A>G), RS1000883985 (16:69331329 G>A), RS1000990978 (16:69332311 C>T), RS1001162459 (16:69337503 A>G), RS1001376123 (16:69333167 T>G), RS1001509095 (16:69337229 A>G), RS1001670729 (16:69329239 T>A), RS1001995505 (16:69338111 C>T)

Disease associations

OMIM: gene MIM:606979 | disease phenotypes: MIM:611182

GenCC curated gene-disease

Disease	Classification	Inheritance
COG8-congenital disorder of glycosylation	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
COG8-congenital disorder of glycosylation	Definitive	AR

Mondo (1): COG8-congenital disorder of glycosylation (MONDO:0012635)

Orphanet (1): COG8-CDG (Orphanet:95428)

HPO phenotypes

76 total (30 of 76 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000233	Thin vermilion border
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000260	Wide anterior fontanel
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000445	Wide nose
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000474	Thickened nuchal skin fold
HP:0000582	Upslanted palpebral fissure
HP:0000657	Oculomotor apraxia
HP:0001137	Alternating esotropia
HP:0001188	Hand clenching
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001274	Agenesis of corpus callosum
HP:0001305	Dandy-Walker malformation
HP:0001310	Dysmetria
HP:0001336	Myoclonus
HP:0001344	Absent speech
HP:0001508	Failure to thrive

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005951_13	Body mass index	5.000000e-11
GCST007006_16	Logical memory (delayed recall) in normal cognition	7.000000e-07
GCST010703_183	Brain morphology (MOSTest)	5.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004874	memory performance
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566987	Congenital Disorder Of Glycosylation, Type IIH (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105880 (SINGLE PROTEIN)

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

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
8.38	Kd	4.165	nM	CHEMBL3752910
8.38	ED50	4.165	nM	CHEMBL3752910
6.09	Kd	819.5	nM	CHEMBL5653589
6.09	ED50	819.5	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	2148110: Binding affinity to human COG8 incubated for 45 mins by Kinobead based pull down assay	kd	0.0042	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148110: Binding affinity to human COG8 incubated for 45 mins by Kinobead based pull down assay	kd	0.8195	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
cadmium sulfate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, affects cotreatment	1
Rosiglitazone	affects cotreatment, decreases expression	1
Pioglitazone	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Troglitazone	decreases expression, decreases reaction	1
Acetaminophen	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	increases expression	1
Methapyrilene	increases methylation	1
Selenium	increases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
tert-Butylhydroperoxide	affects cotreatment, decreases expression, decreases reaction	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
CHEMBL4012606	Binding	Binding affinity to COG8 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)

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