OSBP2

Summary

OSBP2 (oxysterol binding protein 2, HGNC:8504) is a protein-coding gene on chromosome 22q12.2, encoding Oxysterol-binding protein 2 (Q969R2). Mediates the bidirectional lipid exchange between intracellular compartments and the plasma membrane, delivering cholesterol to the plasma membrane while transferring PI(4,5)P(2) to internal organelles, thereby modulating membrane lipid composition and associated signaling pathw….

The protein encoded by this gene contains a pleckstrin homology (PH) domain and an oxysterol-binding region. It binds oxysterols such as 7-ketocholesterol and may inhibit their cytotoxicity. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 23762 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 55 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_030758

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8504
Approved symbol	OSBP2
Name	oxysterol binding protein 2
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1664, ORP-4, ORP4
Ensembl gene	ENSG00000184792
Ensembl biotype	protein_coding
OMIM	606729
Entrez	23762

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000332585, ENST00000401475, ENST00000403222, ENST00000407373, ENST00000424224, ENST00000431368, ENST00000433183, ENST00000437268, ENST00000438716, ENST00000445781, ENST00000446658, ENST00000452656, ENST00000454145, ENST00000464341, ENST00000477355, ENST00000496367, ENST00000496575, ENST00000535268, ENST00000713559, ENST00000915560, ENST00000915561, ENST00000943468, ENST00000943469

RefSeq mRNA: 6 — MANE Select: NM_030758 NM_001282738, NM_001282739, NM_001282740, NM_001282741, NM_001282742, NM_030758

CCDS: CCDS43002, CCDS63446, CCDS63448, CCDS63449, CCDS63450, CCDS63451

Canonical transcript exons

ENST00000332585 — 14 exons

Exon	Start	End
ENSE00001327388	30694874	30695553
ENSE00001618779	30893817	30894001
ENSE00001668048	30890728	30890973
ENSE00001671961	30893638	30893733
ENSE00001681826	30889490	30889636
ENSE00001742048	30889177	30889234
ENSE00001757106	30893122	30893242
ENSE00003479257	30870429	30870682
ENSE00003492403	30893463	30893566
ENSE00003526798	30905837	30906069
ENSE00003531808	30887426	30887618
ENSE00003626206	30888223	30888340
ENSE00003730291	30741161	30741369
ENSE00003844494	30906197	30907813

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 96.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.3744 / max 929.3315, expressed in 1136 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191719	4.4811	255
191714	1.3965	678
191717	1.0702	267
191715	0.5462	261
191721	0.2593	53
191720	0.2080	48
191722	0.1578	26
191718	0.1235	43
191713	0.0869	38
209450	0.0299	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.41	gold quality
left testis	UBERON:0004533	89.87	gold quality
right testis	UBERON:0004534	89.43	gold quality
monocyte	CL:0000576	88.82	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.56	gold quality
cerebellar hemisphere	UBERON:0002245	87.91	gold quality
cerebellar cortex	UBERON:0002129	87.89	gold quality
mononuclear cell	CL:0000842	87.88	gold quality
testis	UBERON:0000473	87.16	gold quality
cerebellum	UBERON:0002037	86.83	gold quality
leukocyte	CL:0000738	86.78	gold quality
blood	UBERON:0000178	86.15	gold quality
prefrontal cortex	UBERON:0000451	85.95	gold quality
right frontal lobe	UBERON:0002810	85.85	gold quality
trabecular bone tissue	UBERON:0002483	85.52	gold quality
male germ cell	CL:0000015	85.04	gold quality
sperm	CL:0000019	85.02	gold quality
primary visual cortex	UBERON:0002436	84.67	gold quality
pituitary gland	UBERON:0000007	84.56	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.38	gold quality
type B pancreatic cell	CL:0000169	84.10	gold quality
olfactory bulb	UBERON:0002264	84.05	gold quality
cortical plate	UBERON:0005343	83.84	gold quality
adrenal tissue	UBERON:0018303	83.60	gold quality
frontal cortex	UBERON:0001870	83.56	gold quality
bone marrow	UBERON:0002371	83.47	gold quality
neocortex	UBERON:0001950	83.32	gold quality
cingulate cortex	UBERON:0003027	83.22	gold quality
anterior cingulate cortex	UBERON:0009835	83.21	gold quality
adenohypophysis	UBERON:0002196	83.19	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	363.40
E-MTAB-7316	yes	34.30
E-GEOD-137537	yes	25.67
E-MTAB-9221	yes	13.71
E-ANND-3	yes	6.84

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

89 targeting OSBP2, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-7150	99.62	66.80	1322

Literature-anchored findings (GeneRIF, showing 14)

• OSBP2 has a role in chronic myeloid leukemia (PMID:12964051)
• Thus the sterol-binding domain of ORP4 binds vimentin, cholesterol and oxysterols, and interacts with the filamentous vimentin network. (PMID:17350617)
• a possible role of OSBP2 gene in the pathogenesis of oxidative damage to the macula induced by oxysterols in age-related macular degeneration patients. (PMID:18294060)
• In preliminary results, significantly higher levels of OSBP2 and OSBPL-7 mRNA were seen in blood samples from cholangiocarcinoma patients than in healthy controls. (PMID:21763455)
• Inhibition of HCV replication by oxysterol-binding protein-related protein 4 (ORP4) through interaction with HCV NS5B and alteration of lipid droplet formation. (PMID:24069433)
• ORP4 promotes the survival of rapidly proliferating cells. (PMID:24742681)
• The authors uncovered a signalling pathway operating specifically in T-cell acute lymphoblastic leukemia cells in which ORP4L mediates G protein-coupled ligand-induced PLCbeta3 activation, resulting in an increase of mitochondrial respiration for cell survival. (PMID:27581363)
• High ORP4L expression is associated with cervical carcinoma. (PMID:27588468)
• ORP4L is crucial for macrophage survival and plays a role in the development of atherosclerosis. (PMID:27729467)
• ORP4L interacts with the trans-Golgi networt in an sterol- and phosphatidylinositol 4-phosphate -dependent manner. (PMID:29930082)
• This study reveals detailed mechanistic insight into the role of ORP4L in PLCbeta3 redistribution from storage within the nucleus to the plasma membrane via RAN activation and interaction with VAPA in Jurkat T-cells. (PMID:30237164)
• ORP4L is a cofactor of ITPR1. (PMID:31648575)
• ORP4L is a prerequisite for the induction of T-cell leukemogenesis associated with human T-cell leukemia virus 1. (PMID:34797912)
• Integrated analysis of histone lysine lactylation (Kla)-specific genes suggests that NR6A1, OSBP2 and UNC119B are novel therapeutic targets for hepatocellular carcinoma. (PMID:37903971)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	osbp2b	ENSDARG00000022772
mus_musculus	Osbp2	ENSMUSG00000020435
rattus_norvegicus	Osbp2	ENSRNOG00000019645

Paralogs (11): OSBPL7 (ENSG00000006025), OSBPL5 (ENSG00000021762), OSBPL3 (ENSG00000070882), OSBPL6 (ENSG00000079156), OSBPL8 (ENSG00000091039), OSBP (ENSG00000110048), OSBPL9 (ENSG00000117859), OSBPL2 (ENSG00000130703), OSBPL1A (ENSG00000141447), OSBPL10 (ENSG00000144645), OSBPL11 (ENSG00000144909)

Protein

Protein identifiers

Oxysterol-binding protein 2 — Q969R2 (reviewed: Q969R2)

Alternative names: Oxysterol-binding protein-related protein 4

All UniProt accessions (10): A0A0A0MSB4, A0AAA9YHZ8, C9J7J0, C9JS84, Q969R2, H7C001, H7C313, H7C368, H7C428, Q6ZN50

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the bidirectional lipid exchange between intracellular compartments and the plasma membrane, delivering cholesterol to the plasma membrane while transferring PI(4,5)P(2) to internal organelles, thereby modulating membrane lipid composition and associated signaling pathways. Binds 7-ketocholesterol. Acts during spermatid development where its function is required prior to the removal of cytoplasm from the sperm head.

Subunit / interactions. Interacts with CCDC159.

Subcellular location. Membrane. Cytoplasmic vesicle. Secretory vesicle. Acrosome.

Tissue specificity. Expressed mainly in retina, testis, and fetal liver.

Similarity. Belongs to the OSBP family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q969R2-1	1	yes
Q969R2-2	2
Q969R2-3	3
Q969R2-4	4
Q969R2-5	5
Q969R2-6	6

RefSeq proteins (6): NP_001269667, NP_001269668, NP_001269669, NP_001269670, NP_001269671, NP_110385* (*=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

Catalyzed reactions (Rhea), 1 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate)(out) + cholesterol(in) = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate)(in) + cholesterol(out) (RHEA:84879)

UniProt features (24 total): splice variant 7, region of interest 6, compositionally biased region 4, modified residue 2, sequence conflict 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969R2-F1	71.97	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.

Post-translational modifications (2): 287, 763

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 140 (showing top): AGGAAGC_MIR5163P, BENPORATH_ES_WITH_H3K27ME3, GOCC_SECRETORY_GRANULE, GOBP_MALE_GAMETE_GENERATION, SP1_Q2_01, GNF2_ANK1, PATIL_LIVER_CANCER, GNF2_SPTA1, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOCC_NEURON_PROJECTION, LEE_CALORIE_RESTRICTION_NEOCORTEX_UP, GOBP_LIPID_LOCALIZATION, NAKAMURA_METASTASIS_MODEL_DN, TGCCTTA_MIR124A

GO Biological Process (5): lipid transport (GO:0006869), spermatid development (GO:0007286), spermatogenesis (GO:0007283), sterol transport (GO:0015918), cell differentiation (GO:0030154)

GO Molecular Function (5): cholesterol binding (GO:0015485), protein binding (GO:0005515), lipid binding (GO:0008289), sterol binding (GO:0032934), sterol transfer activity (GO:0120015)

GO Cellular Component (9): acrosomal vesicle (GO:0001669), cytosol (GO:0005829), plasma membrane (GO:0005886), perinuclear endoplasmic reticulum (GO:0097038), apical dendrite (GO:0097440), nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
cellular anatomical structure	3
sterol binding	2
binding	2
intracellular membrane-bounded organelle	2
transport	1
lipid localization	1
germ cell development	1
spermatid differentiation	1
developmental process involved in reproduction	1
male gamete generation	1
lipid transport	1
organic hydroxy compound transport	1
cellular developmental process	1
alcohol binding	1
steroid binding	1
sterol transport	1
lipid transfer activity	1
secretory granule	1
membrane	1
cell periphery	1
endoplasmic reticulum	1
perinuclear region of cytoplasm	1
dendrite	1
endomembrane system	1
intracellular vesicle	1

Protein interactions and networks

STRING

898 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OSBP2	HSCB	Q8IWL3	810
OSBP2	UQCR10	Q9UDW1	810
OSBP2	VAPA	Q9P0L0	788
OSBP2	PLEK2	Q9NYT0	727
OSBP2	PLEK	P08567	725
OSBP2	OSBPL9	Q96SU4	671
OSBP2	OSBPL3	Q9H4L5	476
OSBP2	OSBPL8	Q9BZF1	474
OSBP2	OSBPL5	Q9H0X9	468
OSBP2	OSBPL11	Q9BXB4	464
OSBP2	OSBPL10	Q9BXB5	459
OSBP2	GXYLT2	A0PJZ3	450
OSBP2	PI4KB	P78405	427
OSBP2	LZTS1	Q9Y250	404
OSBP2	ARL15	Q9NXU5	397

IntAct

28 interactions, top by confidence:

A	B	Type	Score
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.640
VAPA	PITPNM1	psi-mi:“MI:0914”(association)	0.640
LNX1	OSBP2	psi-mi:“MI:0915”(physical association)	0.560
OSBP2	LNX1	psi-mi:“MI:0915”(physical association)	0.560
	OSBP2	psi-mi:“MI:0403”(colocalization)	0.460
	OSBP2	psi-mi:“MI:0915”(physical association)	0.460
OSBP2	MAP1LC3B	psi-mi:“MI:0915”(physical association)	0.400
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
OSBP2	TNNT1	psi-mi:“MI:0915”(physical association)	0.370
RNASEH2A	PHF20L1	psi-mi:“MI:0914”(association)	0.350
BTNL8	TMEM131L	psi-mi:“MI:0914”(association)	0.350
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.350
OSBP	ESYT2	psi-mi:“MI:0914”(association)	0.350
VAPA	ESYT2	psi-mi:“MI:0914”(association)	0.350
FKBP6	VGF	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350

BioGRID (36): LNX1 (Two-hybrid), OSBP2 (Affinity Capture-RNA), OSBP2 (Affinity Capture-RNA), OSBP2 (Affinity Capture-MS), OSBP2 (Affinity Capture-MS), OSBP2 (Synthetic Growth Defect), OSBP2 (Affinity Capture-MS), OSBP2 (Affinity Capture-MS), OSBP2 (Affinity Capture-MS), OSBP2 (Affinity Capture-MS), OSBP2 (Affinity Capture-RNA), OSBP2 (Affinity Capture-RNA), OSBP2 (Two-hybrid), OSBP2 (Two-hybrid), OSBP2 (Two-hybrid)

ESM2 similar proteins: A0A8I3NFE2, A0FI79, B1AVH7, B5DFA1, D2H0G5, D7PF45, O00750, O15357, O70143, P29353, P97573, P98083, Q00IB7, Q0IIE2, Q15678, Q16825, Q17R13, Q2I6J0, Q2I6J1, Q2V2M9, Q5JV73, Q5M824, Q5R7W7, Q5U2X5, Q61120, Q62130, Q62136, Q62728, Q62925, Q69Z98, Q6P4S2, Q6P549, Q80TI1, Q8AY68, Q8BMC3, Q8BYW1, Q8IWQ3, Q8K245, Q92529, Q92835

Diamond homologs: A0A223HDI2, A2BG43, B0BLT4, B0BNM9, B0YN54, D2KC46, D3ZY60, F1MS15, O14340, O22797, O95397, P16258, P22059, P35845, P68265, P68266, Q12451, Q3B7Z2, Q5M7Y0, Q5QNQ6, Q5R6M6, Q5U3N0, Q63ZQ3, Q6NRZ4, Q6NTN5, Q6NU44, Q6P3Q6, Q6VVX2, Q80W71, Q8C115, Q8IVE3, Q969R2, Q96JA3, Q9EQG9, Q9ERS4, Q9GKI7, Q9HB20, Q9JL62, Q9NZD2, Q9SAF0

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
GSK3B	“up-regulates activity”	OSBP2	phosphorylation
GSK3A	“up-regulates activity”	OSBP2	phosphorylation
MAPK8	“up-regulates activity”	OSBP2	phosphorylation
CSNK1A1	“up-regulates activity”	OSBP2	phosphorylation
CDK1	“up-regulates activity”	OSBP2	phosphorylation
OSBP2	“up-regulates quantity”	cholesterol	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	4
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

4020 predictions. Top by Δscore:

Variant	Effect	Δscore
22:30695550:ACAGG:A	donor_loss	1.0000
22:30695551:CAG:C	donor_loss	1.0000
22:30695552:AG:A	donor_loss	1.0000
22:30695553:GG:G	donor_loss	1.0000
22:30695554:G:C	donor_loss	1.0000
22:30695555:T:A	donor_loss	1.0000
22:30731478:C:CA	acceptor_gain	1.0000
22:30741153:T:G	acceptor_gain	1.0000
22:30741159:A:AG	acceptor_gain	1.0000
22:30741160:G:GG	acceptor_gain	1.0000
22:30741160:GA:G	acceptor_gain	1.0000
22:30741160:GAA:G	acceptor_gain	1.0000
22:30741370:GTA:G	donor_gain	1.0000
22:30870424:CACA:C	acceptor_loss	1.0000
22:30870425:A:AG	acceptor_gain	1.0000
22:30870426:C:G	acceptor_gain	1.0000
22:30870427:A:AG	acceptor_gain	1.0000
22:30870427:A:C	acceptor_loss	1.0000
22:30870427:AGAT:A	acceptor_gain	1.0000
22:30870428:G:GG	acceptor_gain	1.0000
22:30870428:GA:G	acceptor_gain	1.0000
22:30870428:GAT:G	acceptor_gain	1.0000
22:30870428:GATG:G	acceptor_gain	1.0000
22:30870428:GATGA:G	acceptor_gain	1.0000
22:30870678:TCAAC:T	donor_gain	1.0000
22:30870683:G:GG	donor_gain	1.0000
22:30887424:A:AG	acceptor_gain	1.0000
22:30887424:AG:A	acceptor_gain	1.0000
22:30887425:G:GG	acceptor_gain	1.0000
22:30887425:GG:G	acceptor_gain	1.0000

AlphaMissense

5968 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:30695482:G:C	K191N	1.000
22:30695482:G:T	K191N	1.000
22:30870522:T:C	L316P	1.000
22:30870540:T:C	L322P	1.000
22:30870564:T:C	L330P	1.000
22:30870644:G:C	A357P	1.000
22:30870651:T:C	L359P	1.000
22:30870657:G:C	R361P	1.000
22:30870660:T:C	I362T	1.000
22:30889583:T:A	W524R	1.000
22:30889583:T:C	W524R	1.000
22:30889608:G:A	G532D	1.000
22:30889617:T:A	L535H	1.000
22:30890762:G:C	R553P	1.000
22:30890885:G:C	R594P	1.000
22:30890904:C:A	N600K	1.000
22:30890904:C:G	N600K	1.000
22:30893173:T:A	W641R	1.000
22:30893173:T:C	W641R	1.000
22:30893209:T:C	F653L	1.000
22:30893210:T:C	F653S	1.000
22:30893210:T:G	F653C	1.000
22:30893211:C:A	F653L	1.000
22:30893211:C:G	F653L	1.000
22:30893215:G:A	G655R	1.000
22:30893215:G:C	G655R	1.000
22:30893216:G:A	G655E	1.000
22:30893216:G:T	G655V	1.000
22:30893507:T:A	W679R	1.000
22:30893507:T:C	W679R	1.000

dbSNP variants (sampled 300 via entrez): RS1000006572 (22:30832326 C>G,T), RS1000051704 (22:30869817 C>G), RS1000063537 (22:30903813 C>G), RS1000064524 (22:30826313 A>G,T), RS1000068484 (22:30845411 G>A), RS1000088781 (22:30696404 A>G), RS1000092600 (22:30696514 C>T), RS1000099573 (22:30754771 C>T), RS1000115237 (22:30745712 T>A,C,G), RS1000115521 (22:30783537 G>C), RS1000136060 (22:30832393 C>A,T), RS1000146817 (22:30805205 T>G), RS1000184368 (22:30702554 C>T), RS1000211966 (22:30874989 C>A), RS1000224785 (22:30776974 T>A,C)

Disease associations

OMIM: gene MIM:606729 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002003_2	Adverse response to chemotherapy (neutropenia/leucopenia) (gemcitabine)	4.000000e-06
GCST007316_4	Response to ketamine in bipolar disorder or major depression (antidepressant effects)	6.000000e-06
GCST007646_1	Estimated glomerular filtration rate change in renal transplantation (donor effect)	7.000000e-07
GCST010002_80	Refractive error	2.000000e-09
GCST011936_2	Takayasu arteritis	6.000000e-06
GCST011939_34	Takayasu arteritis	6.000000e-06
GCST90002404_592	Red cell distribution width	3.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007006	depressive symptom measurement
EFO:0009748	response to ketamine
EFO:0005199	renal transplant outcome measurement
EFO:0007892	donor genotype effect measurement
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465343 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 747,957 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL112570	CHOLESTEROL	2	747,957

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

Binding affinities (BindingDB)

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

Ligand	Measure	Value
(1S,2R,5S,10S,11S,14R,15R)-14-[(2R)-6-hydroxy-6-methylheptan-2-yl]-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-7-en-5-ol	KD	23 nM

ChEMBL bioactivities

11 potent at pChembl≥5 of 11 total, top 11 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.29	Ki	51	nM	CHEMBL5429365
7.27	Kd	54	nM	CHEMBL169046
7.17	Kd	68	nM	CHOLESTEROL
7.15	Ki	71	nM	CHEMBL375269
7.11	Ki	78	nM	CEPHALOSTATIN 1
7.04	Ki	92	nM	CHEMBL4788348
7.01	Ki	98	nM	CHEMBL5405099
6.50	Ki	320	nM	CHEMBL173898
6.40	Ki	400	nM	CHEMBL171804
6.11	Ki	780	nM	CHEMBL5424616
5.58	Ki	2600	nM	SCHWEINFURTHIN A

PubChem BioAssay actives

15 with measured affinity, of 34 total; 11 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
(3S,8S,9S,10R,13R,14S,17R)-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol	1802835: Sterol-Binding Assay from Article 10.1074/jbc.M114.571216: “Oxysterol-binding protein (OSBP)-related protein 4 (ORP4) is essential for cell proliferation and survival.”	kd	0.0170	uM
(3S,8R,9S,10S,13R,14S,17R)-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol	1968553: Displacement of [3H]-25-OHC from human ORP4 overexpressed in HEK293T cell lysate assessed as inhibition constant by competitive binding assay	ki	0.0510	uM
Cholesterol	1802835: Sterol-Binding Assay from Article 10.1074/jbc.M114.571216: “Oxysterol-binding protein (OSBP)-related protein 4 (ORP4) is essential for cell proliferation and survival.”	kd	0.0600	uM
[(2S,3R,4S,5R)-2-[(2S,3R,4S,5S)-3-acetyloxy-2-[[(3S,8R,9S,10R,13S,14S,16S,17S)-3,17-dihydroxy-10,13-dimethyl-17-[(2S)-6-methyl-3-oxoheptan-2-yl]-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-16-yl]oxy]-5-hydroxyoxan-4-yl]oxy-4,5-dihydroxyoxan-3-yl] 4-methoxybenzoate	1968549: Displacement of [3H]-25-OHC from human ORP4 overexpressed in HEK293T cell lysate assessed as inhibition constant	ki	0.0710	uM
10328411	1968549: Displacement of [3H]-25-OHC from human ORP4 overexpressed in HEK293T cell lysate assessed as inhibition constant	ki	0.0780	uM
(3S,7S,8S,9S,10R,13R,14S,17R)-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-3,7-diol	1968553: Displacement of [3H]-25-OHC from human ORP4 overexpressed in HEK293T cell lysate assessed as inhibition constant by competitive binding assay	ki	0.0920	uM
(3S,8R,9S,10R,13S,14S,17S)-10,13,16,16-tetramethyl-3-(oxan-2-yloxy)-1,2,3,4,7,8,9,11,12,14,15,17-dodecahydrocyclopenta[a]phenanthren-17-ol	1968549: Displacement of [3H]-25-OHC from human ORP4 overexpressed in HEK293T cell lysate assessed as inhibition constant	ki	0.0980	uM
(3S,8S,9S,10R,13S,14S,17S)-17-[(2S)-2-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol	1968553: Displacement of [3H]-25-OHC from human ORP4 overexpressed in HEK293T cell lysate assessed as inhibition constant by competitive binding assay	ki	0.3200	uM
(3S,8S,9S,10R,13R,14S,17R)-17-[(2R,5S)-5-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol	1968553: Displacement of [3H]-25-OHC from human ORP4 overexpressed in HEK293T cell lysate assessed as inhibition constant by competitive binding assay	ki	0.4000	uM
(3S,8S,9S,10R,13S,14S,17S)-17-[(2S)-2-hydroxyheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol	1968553: Displacement of [3H]-25-OHC from human ORP4 overexpressed in HEK293T cell lysate assessed as inhibition constant by competitive binding assay	ki	0.7800	uM
(2S,3R,4aR,9aR)-7-[(E)-2-[4-[(2E)-3,7-dimethylocta-2,6-dienyl]-3,5-dihydroxyphenyl]ethenyl]-1,1,4a-trimethyl-3,4,9,9a-tetrahydro-2H-xanthene-2,3,5-triol	1968549: Displacement of [3H]-25-OHC from human ORP4 overexpressed in HEK293T cell lysate assessed as inhibition constant	ki	2.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression	3
Acetaminophen	decreases expression, increases expression	3
Valproic Acid	affects cotreatment, decreases expression	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Cisplatin	affects expression, affects cotreatment, decreases expression	2
Diethylhexyl Phthalate	decreases expression, increases abundance, increases methylation	2
Estradiol	affects cotreatment, decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
kojic acid	decreases expression	1
trichostatin A	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
1,6-hexamethylene diisocyanate	affects expression	1
trimellitic anhydride	affects expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
ammonium hexachloroplatinate	affects expression	1
benzo(e)pyrene	decreases methylation	1
cupric chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5320823	Binding	Displacement of [3H]-25-OHC from human ORP4 overexpressed in HEK293T cell lysate assessed as inhibition constant	Structure-Activity Relationships of Ligand Binding to Oxysterol-Binding Protein (OSBP) and OSBP-Related Protein 4. — J Med Chem

Clinical trials (associated diseases)

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