OSBPL8

Summary

OSBPL8 (oxysterol binding protein like 8, HGNC:16396) is a protein-coding gene on chromosome 12q21.2, encoding Oxysterol-binding protein-related protein 8 (Q9BZF1). Lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane: specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P, whic….

This gene encodes a member of a family of proteins containing an N-terminal pleckstrin homology domain and a highly conserved C-terminal oxysterol-binding protein-like sterol-binding domain. It binds mutliple lipid-containing molecules, including phosphatidylserine, phosphatidylinositol 4-phosphate (PI4P) and oxysterol, and promotes their exchange between the endoplasmic reticulum and the plasma membrane. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 114882 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 94 total
• Druggable target: yes
• MANE Select transcript: NM_020841

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16396
Approved symbol	OSBPL8
Name	oxysterol binding protein like 8
Location	12q21.2
Locus type	gene with protein product
Status	Approved
Aliases	OSBP10, ORP8, MST120, MSTP120
Ensembl gene	ENSG00000091039
Ensembl biotype	protein_coding
OMIM	606736
Entrez	114882

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 14 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000261183, ENST00000393249, ENST00000393250, ENST00000546946, ENST00000547540, ENST00000547544, ENST00000548341, ENST00000548485, ENST00000548535, ENST00000549570, ENST00000549646, ENST00000550628, ENST00000550865, ENST00000551927, ENST00000552178, ENST00000552586, ENST00000553139, ENST00000611266, ENST00000951801

RefSeq mRNA: 5 — MANE Select: NM_020841 NM_001003712, NM_001319652, NM_001319653, NM_001319655, NM_020841

CCDS: CCDS31862, CCDS41814

Canonical transcript exons

ENST00000261183 — 24 exons

Exon	Start	End
ENSE00000910567	76358706	76358811
ENSE00001132027	76356626	76356728
ENSE00001597818	76375273	76375370
ENSE00001623708	76384254	76384350
ENSE00001630458	76386168	76386266
ENSE00001637874	76394645	76394729
ENSE00001642871	76371448	76371584
ENSE00001655314	76378452	76378550
ENSE00001660315	76459859	76459895
ENSE00001698540	76369214	76369301
ENSE00001714426	76399873	76399974
ENSE00001729796	76397694	76397897
ENSE00001738103	76402689	76402766
ENSE00001744750	76390420	76390657
ENSE00001786515	76373344	76373433
ENSE00001786637	76389645	76389829
ENSE00002425593	76351797	76356021
ENSE00003465958	76410564	76410634
ENSE00003515427	76487510	76487618
ENSE00003518068	76369637	76369822
ENSE00003543163	76392581	76392752
ENSE00003551237	76450851	76450988
ENSE00003583537	76386579	76386660
ENSE00003850279	76559397	76559771

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 98.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.2826 / max 891.8300, expressed in 1824 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132224	22.0188	1768
132222	12.1720	1758
132225	6.3139	1661
132223	2.8215	1338
132220	2.3741	1220
132221	0.3375	136
132203	0.1383	66
132219	0.0995	43
132205	0.0059	2
132204	0.0011	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	98.57	gold quality
mammary duct	UBERON:0001765	98.54	gold quality
trabecular bone tissue	UBERON:0002483	98.46	gold quality
endothelial cell	CL:0000115	98.42	gold quality
nipple	UBERON:0002030	98.37	gold quality
skin of hip	UBERON:0001554	98.24	gold quality
calcaneal tendon	UBERON:0003701	98.19	gold quality
visceral pleura	UBERON:0002401	98.07	gold quality
trigeminal ganglion	UBERON:0001675	97.86	gold quality
superficial temporal artery	UBERON:0001614	97.70	gold quality
epithelium of mammary gland	UBERON:0003244	97.70	gold quality
lateral globus pallidus	UBERON:0002476	97.68	gold quality
upper leg skin	UBERON:0004262	97.68	gold quality
oral cavity	UBERON:0000167	97.42	gold quality
pleura	UBERON:0000977	97.37	gold quality
dorsal root ganglion	UBERON:0000044	97.36	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.33	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.27	gold quality
parietal pleura	UBERON:0002400	97.25	gold quality
cauda epididymis	UBERON:0004360	97.25	gold quality
tongue squamous epithelium	UBERON:0006919	97.18	gold quality
mammalian vulva	UBERON:0000997	97.05	gold quality
entorhinal cortex	UBERON:0002728	97.04	gold quality
pericardium	UBERON:0002407	96.99	gold quality
hair follicle	UBERON:0002073	96.97	gold quality
renal medulla	UBERON:0000362	96.77	gold quality
penis	UBERON:0000989	96.72	gold quality
nephron tubule	UBERON:0001231	96.71	gold quality
postcentral gyrus	UBERON:0002581	96.64	gold quality
parietal lobe	UBERON:0001872	96.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8911	no	254.32
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

297 targeting OSBPL8, 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-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4776-3P	100.00	68.73	1340
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-656-3P	100.00	72.15	2788
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-181A-5P	99.99	72.96	2995

Literature-anchored findings (GeneRIF, showing 15)

• occurrence of an unusual TG 3’ splice site in intron 2 (PMID:17672918)
• Data identify ORP8 as a negative regulator of ABCA1 expression and macrophage cholesterol efflux. ORP8 may, thus, modulate the development of atherosclerosis. (PMID:17991739)
• results reveal that ORP8 has the capacity to modulate lipid homeostasis and SREBP activity, probably through an indirect mechanism, and provide clues of an entirely new mode of ORP action (PMID:21698267)
• ORP8 overexpression resulted in reduced expression of the aP2 mRNA, while down-regulation of adiponectin and aP2 was observed in ORP11 silenced cells. ORP8 overexpression or silencing of ORP11 markedly decreased cellular triglyceride storage. (PMID:23028956)
• Data indicate that miR-143 impairs insulin action via downregulation of oxysterol-binding protein-related protein 8 (ORP8). (PMID:24333576)
• role of ORP8 in Fas translocation to the plasma membrane and its down-regulation by miR-143 offer a putative mechanistic explanation for HCC resistance to apoptosis (PMID:25596532)
• ORP5 and ORP8 could mediate PI4P/phosphatidylserine (PS) countertransport between the endoplasmic reticulum (ER) and the plasma membrane (PM), thus delivering PI4P to the ER-localized PI4P phosphatase Sac1 for degradation and PS from the ER to the PM. (PMID:26206935)
• mammalian ORP5 and ORP8 proteins localize to ER-mitochondrial MCS, in addition to ER-PM contact sites. (PMID:27113756)
• the present study suggests that ORP8 may mediate the cytotoxicity of 25-hydroxycholesterol. (PMID:27530118)
• we found that overexpression of ORP8 significantly inhibits GC cell proliferation and implanted tumor growth in vivo. Induction of ER stress, inhibition of Wnt signaling, and apoptotic cell death are involved in ORP8-induced inhibition of GC cell proliferation. (PMID:27983927)
• ORP5/8 are endoplasmic reticulum (ER) membrane proteins implicated in lipid trafficking that localize to ER-plasma membrane (PM) contacts and maintain membrane homeostasis. Here the authors show that PtdIns(4,5)P 2 plays a critical role in the targeting and function of ORP5/8 at the PM. (PMID:28970484)
• Examination of a series of deletion constructs demonstrated that both the N-terminal polybasic region and the PH domain are required for proper targeting of the short splice variant ORP8S to the PM-ER contact site in Chinese hamster ovary cells. (PMID:29409900)
• ORP5/8 recruitment to the plasma membrane occurs through interactions with the N-terminal Pleckstrin homology domains and adjacent basic residues of ORP5/8 with both phosphatidylinositol 4-phosphate and Phosphatidylinositol 4,5-bisphosphate. (PMID:29472386)
• ORP5/8 regulate Ca(2+) signaling at specific membrane contact sites foci. (PMID:29748134)
• ORP8 induces apoptosis by releasing cytochrome c from mitochondria in nonsmall cell lung cancer. (PMID:32323800)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	OSBPL8	ENSDARG00000039724
mus_musculus	Osbpl8	ENSMUSG00000020189
rattus_norvegicus	Osbpl8	ENSRNOG00000026962
drosophila_melanogaster	CG3860	FBGN0034951
caenorhabditis_elegans		WBGENE00008832

Paralogs (11): OSBPL7 (ENSG00000006025), OSBPL5 (ENSG00000021762), OSBPL3 (ENSG00000070882), OSBPL6 (ENSG00000079156), OSBP (ENSG00000110048), OSBPL9 (ENSG00000117859), OSBPL2 (ENSG00000130703), OSBPL1A (ENSG00000141447), OSBPL10 (ENSG00000144645), OSBPL11 (ENSG00000144909), OSBP2 (ENSG00000184792)

Protein

Protein identifiers

Oxysterol-binding protein-related protein 8 — Q9BZF1 (reviewed: Q9BZF1)

All UniProt accessions (10): Q9BZF1, F8VQX7, F8VS33, F8VUA7, F8VVD3, F8VVE7, F8VZ43, F8VZB8, F8W060, F8W1F1

UniProt curated annotations — full annotation on UniProt →

Function. Lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane: specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum. Binds phosphatidylserine and PI4P in a mutually exclusive manner. Binds oxysterol, 25-hydroxycholesterol and cholesterol.

Subunit / interactions. Interacts with SPAG5. Interacts with NUP62.

Subcellular location. Endoplasmic reticulum membrane. Nucleus membrane Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed. Expressed at higher level in macrophages.

Similarity. Belongs to the OSBP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BZF1-1	1, ORP8L	yes
Q9BZF1-2	2
Q9BZF1-3	3, ORP8S

RefSeq proteins (5): NP_001003712, NP_001306581, NP_001306582, NP_001306584, NP_065892* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000648	Oxysterol-bd	Family
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR018494	Oxysterol-bd_CS	Conserved_site
IPR037239	OSBP_sf	Homologous_superfamily

Pfam: PF00169, PF01237

UniProt features (50 total): modified residue 11, compositionally biased region 9, binding site 9, strand 8, region of interest 3, splice variant 2, helix 2, chain 1, transmembrane region 1, domain 1, mutagenesis site 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5U78	X-RAY DIFFRACTION	1.98
5U77	X-RAY DIFFRACTION	2.16
8P7A	X-RAY DIFFRACTION	2.56
1V88	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZF1-F1	70.76	0.39

Functional residue map

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

Ligand- & substrate-binding residues (9): 420–425; 420–425; 482–485; 485; 514–515; 540; 706; 710; 714

Post-translational modifications (11): 1, 14, 65, 68, 314, 328, 342, 807, 808, 810, 814

Mutagenesis-validated functional residues (1):

Position	Phenotype
514–515	impaired lipid countertransport between the endoplasmic reticulum and the plasma membrane.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1482801	Acyl chain remodelling of PS

MSigDB gene sets: 349 (showing top): GOBP_PHOSPHATIDYLSERINE_ACYL_CHAIN_REMODELING, GGGACCA_MIR133A_MIR133B, GOBP_ACYLGLYCEROL_HOMEOSTASIS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOBP_LIPID_HOMEOSTASIS

GO Biological Process (11): phospholipid transport (GO:0015914), negative regulation of cell migration (GO:0030336), phosphatidylserine acyl-chain remodeling (GO:0036150), fat cell differentiation (GO:0045444), positive regulation of D-glucose import across plasma membrane (GO:0046326), positive regulation of insulin receptor signaling pathway (GO:0046628), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), triglyceride homeostasis (GO:0070328), protein localization to nuclear pore (GO:0090204), lipid transport (GO:0006869), intermembrane lipid transfer (GO:0120009)

GO Molecular Function (7): phosphatidylserine binding (GO:0001786), obsolete phospholipid transporter activity (GO:0005548), cholesterol binding (GO:0015485), phosphatidylinositol-4-phosphate binding (GO:0070273), phosphatidylserine transfer activity (GO:0140343), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (8): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), membrane (GO:0016020), nuclear membrane (GO:0031965), cortical endoplasmic reticulum (GO:0032541), nucleus (GO:0005634), endomembrane system (GO:0012505)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
lipid transport	2
anion binding	2
binding	2
cytoplasm	2
intracellular membrane-bounded organelle	2
organelle membrane	2
organophosphate ester transport	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
phosphatidylserine metabolic process	1
cell differentiation	1
positive regulation of D-glucose transmembrane transport	1
regulation of D-glucose import across plasma membrane	1
D-glucose import across plasma membrane	1
insulin receptor signaling pathway	1
positive regulation of signal transduction	1
regulation of insulin receptor signaling pathway	1
positive regulation of cellular response to insulin stimulus	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
acylglycerol homeostasis	1
protein localization to nuclear envelope	1
transport	1
lipid localization	1
membrane organization	1
phospholipid binding	1
modified amino acid binding	1
sterol binding	1
alcohol binding	1
phosphatidylinositol phosphate binding	1
phospholipid transfer activity	1
endomembrane system	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
nucleus	1
nuclear envelope	1
cell cortex	1

Protein interactions and networks

STRING

1562 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OSBPL8	RMDN3	Q96TC7	989
OSBPL8	PLEK2	Q9NYT0	703
OSBPL8	PLEK	P08567	694
OSBPL8	NUP62	P37198	603
OSBPL8	ESYT2	A0FGR8	570
OSBPL8	VAPA	Q9P0L0	559
OSBPL8	VAPB	O95292	556
OSBPL8	PITPNM1	O00562	544
OSBPL8	USP5	P45974	518
OSBPL8	PI4KA	P42356	518
OSBPL8	C2CD2L	O14523	516
OSBPL8	ESYT1	Q9BSJ8	499
OSBPL8	OSBP	P22059	490
OSBPL8	PDZD8	Q8NEN9	482
OSBPL8	OSBP2	Q969R2	474

IntAct

165 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
OSBPL5	NAGLU	psi-mi:“MI:0914”(association)	0.640
OSBPL8	CSNK2A2	psi-mi:“MI:0914”(association)	0.640
OSBPL8	SPAG5	psi-mi:“MI:0915”(physical association)	0.600
SPAG5	OSBPL8	psi-mi:“MI:0403”(colocalization)	0.600
OSBPL8	SPAG5	psi-mi:“MI:0403”(colocalization)	0.600
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
PDPK1	AGRN	psi-mi:“MI:0914”(association)	0.530
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
EDA	AP3B1	psi-mi:“MI:0914”(association)	0.530
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
HADHA	AGRN	psi-mi:“MI:0914”(association)	0.530
GPR183	NRP1	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CD44	PDPK1	psi-mi:“MI:0914”(association)	0.530
STX3	NBAS	psi-mi:“MI:0914”(association)	0.530
UNC93B1	GPR89A	psi-mi:“MI:0914”(association)	0.530

BioGRID (374): OSBPL8 (Affinity Capture-MS), OSBPL8 (Affinity Capture-MS), OSBPL8 (Affinity Capture-MS), OSBPL8 (Affinity Capture-MS), OSBPL8 (Affinity Capture-MS), OSBPL8 (Affinity Capture-MS), OSBPL8 (Affinity Capture-MS), OSBPL8 (Affinity Capture-MS), OSBPL8 (Affinity Capture-MS), OSBPL8 (Affinity Capture-MS), OSBPL8 (Co-fractionation), OSBPL8 (Affinity Capture-MS), OSBPL8 (Affinity Capture-MS), OSBPL8 (Proximity Label-MS), OSBPL8 (Proximity Label-MS)

ESM2 similar proteins: A1A5G2, A2AFR3, A7MBL8, B9EJ86, E1C1R4, E1C3P4, F1LXF1, O94806, O94967, P0C6S7, P0CAX5, P11274, P22682, Q0V9G5, Q14161, Q14CM0, Q15139, Q16513, Q1RMU2, Q3KR37, Q3LAC4, Q3UGM2, Q5RED8, Q5T6S3, Q5U252, Q62101, Q66H62, Q6DFZ1, Q6P5G6, Q6PAJ1, Q70Z35, Q7Z6G8, Q80TI0, Q80TQ2, Q80YA9, Q8BIZ1, Q8BWW9, Q8BY87, Q8K1Y2, Q8NEL9

Diamond homologs: A0A2Z4HQ03, A2A8Z1, B9EJ86, O43021, O74178, O80866, P0C199, P35844, P38755, Q02201, Q0IJ05, Q54NM4, Q5M7Y0, Q5R6M6, Q5R9W4, Q6NRZ4, Q6P3Q6, Q6VVX2, Q86KG4, Q8BX94, Q8CI95, Q96SU4, Q9BXB4, Q9BXB5, Q9BZF1, Q9EQG9, Q9ER64, Q9GKI7, Q9H0X9, Q9H1P3, Q9UUA1, Q9UW21, Q9UW25, Q9Y5P4, S4R1M9, O94512, Q12451, Q54PS9, Q8S8P9, Q9SVZ9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 206 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
Attachment and Entry	6	25.9×	6e-05
VEGFR2 mediated cell proliferation	5	20.5×	4e-04
HS-GAG degradation	5	17.9×	6e-04
Respiratory syncytial virus (RSV) attachment and entry	5	17.9×	6e-04
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	5	15.2×	8e-04
DAP12 signaling	5	13.2×	1e-03
Signaling by SCF-KIT	6	10.7×	8e-04
NCAM signaling for neurite out-growth	5	9.8×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
insulin receptor signaling pathway	7	8.7×	5e-03
protein autophosphorylation	10	8.2×	6e-04
cell surface receptor protein tyrosine kinase signaling pathway	8	7.8×	4e-03
positive regulation of MAPK cascade	12	5.4×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4366 predictions. Top by Δscore:

Variant	Effect	Δscore
12:76355894:TGA:T	donor_gain	1.0000
12:76356729:C:CC	acceptor_gain	1.0000
12:76369210:ATACC:A	donor_loss	1.0000
12:76369211:TACC:T	donor_loss	1.0000
12:76369297:GGGTA:G	acceptor_gain	1.0000
12:76369298:GGTA:G	acceptor_gain	1.0000
12:76369299:GTA:G	acceptor_gain	1.0000
12:76369299:GTAC:G	acceptor_loss	1.0000
12:76369300:TA:T	acceptor_gain	1.0000
12:76369300:TACTA:T	acceptor_loss	1.0000
12:76369301:ACT:A	acceptor_loss	1.0000
12:76369302:C:CC	acceptor_gain	1.0000
12:76369303:T:C	acceptor_loss	1.0000
12:76369306:A:C	acceptor_gain	1.0000
12:76369310:A:AC	acceptor_gain	1.0000
12:76369310:A:C	acceptor_gain	1.0000
12:76369631:A:AC	donor_gain	1.0000
12:76369632:C:CC	donor_gain	1.0000
12:76369632:CTTA:C	donor_gain	1.0000
12:76369633:TTAC:T	donor_loss	1.0000
12:76369634:TACT:T	donor_loss	1.0000
12:76369635:A:AC	donor_gain	1.0000
12:76369635:ACT:A	donor_gain	1.0000
12:76369635:ACTCT:A	donor_loss	1.0000
12:76369636:C:CC	donor_gain	1.0000
12:76369636:CT:C	donor_gain	1.0000
12:76369636:CTC:C	donor_gain	1.0000
12:76369636:CTCT:C	donor_gain	1.0000
12:76369636:CTCTG:C	donor_gain	1.0000
12:76369818:AGAGT:A	acceptor_gain	1.0000

AlphaMissense

5873 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:76369291:A:G	W751R	1.000
12:76369291:A:T	W751R	1.000
12:76369735:T:A	R714S	1.000
12:76369735:T:G	R714S	1.000
12:76369736:C:G	R714T	1.000
12:76369747:T:A	E710D	1.000
12:76369747:T:G	E710D	1.000
12:76369759:C:A	K706N	1.000
12:76369759:C:G	K706N	1.000
12:76369761:T:C	K706E	1.000
12:76369761:T:G	K706Q	1.000
12:76369818:A:G	W687R	1.000
12:76369818:A:T	W687R	1.000
12:76373346:A:G	W639R	1.000
12:76373346:A:T	W639R	1.000
12:76375315:A:C	C595W	1.000
12:76378545:A:G	S546P	1.000
12:76378550:C:T	G544E	1.000
12:76384341:G:C	H515D	1.000
12:76384344:G:C	H514D	1.000
12:76386215:A:G	W496R	1.000
12:76386215:A:T	W496R	1.000
12:76386246:A:C	N485K	1.000
12:76386246:A:T	N485K	1.000
12:76386248:T:C	N485D	1.000
12:76386253:G:T	P483H	1.000
12:76386611:A:G	W468R	1.000
12:76386611:A:T	W468R	1.000
12:76389713:A:C	F428L	1.000
12:76389713:A:T	F428L	1.000

dbSNP variants (sampled 300 via entrez): RS1000014590 (12:76508576 T>C), RS1000023278 (12:76422415 T>C), RS1000029347 (12:76438226 T>C), RS1000034918 (12:76380162 A>C), RS1000046194 (12:76540533 G>A), RS1000052227 (12:76542558 A>G), RS1000065702 (12:76377203 CTT>C), RS1000069028 (12:76425579 C>A,T), RS1000073098 (12:76515497 A>G), RS1000080180 (12:76370901 A>G), RS1000131409 (12:76468826 T>C), RS1000136764 (12:76509349 G>T), RS1000137269 (12:76424160 C>T), RS1000173759 (12:76534496 A>G), RS1000174582 (12:76473688 C>G,T)

Disease associations

OMIM: gene MIM:606736 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009391_1807	Metabolite levels	9.000000e-06
GCST009391_841	Metabolite levels	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010403	triacylglycerol 48:0 measurement
EFO:0010400	triacylglycerol 46:0 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067075 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.89	Kd	127.5	nM	CHEMBL3752910
6.89	ED50	127.5	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 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	2148918: Binding affinity to human OSBPL8 incubated for 45 mins by Kinobead based pull down assay	kd	0.1275	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	3
methylmercuric chloride	increases expression	2
bisphenol A	decreases methylation, increases expression	2
trichostatin A	affects expression, decreases expression	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
bisphenol S	decreases methylation, affects cotreatment, increases expression	2
Acetaminophen	affects expression, increases expression	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Ozone	increases oxidation, increases abundance, affects cotreatment	2
Quercetin	decreases expression, increases phosphorylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
geldanamycin	increases expression	1
testosterone enanthate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenate	increases abundance, increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	decreases expression	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	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
CHEMBL5651960	Binding	Binding affinity to human OSBPL8 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)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery