OSBPL3

Summary

OSBPL3 (oxysterol binding protein like 3, HGNC:16370) is a protein-coding gene on chromosome 7p15.3, encoding Oxysterol-binding protein-related protein 3 (Q9H4L5). Lipid transfer protein that mediates the non-vesicular transport of phosphoinositide 4-phosphate (1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate), or PI(4)P) at the plasma membrane (PM)/ endoplasmic reticulum (ER) contact sites.

This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. The encoded protein is involved in the regulation of cell adhesion and organization of the actin cytoskeleton. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 26031 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 150 total
• Druggable target: yes
• MANE Select transcript: NM_015550

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16370
Approved symbol	OSBPL3
Name	oxysterol binding protein like 3
Location	7p15.3
Locus type	gene with protein product
Status	Approved
Aliases	ORP-3, ORP3, KIAA0704
Ensembl gene	ENSG00000070882
Ensembl biotype	protein_coding
OMIM	606732
Entrez	26031

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 13 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000313367, ENST00000396429, ENST00000396431, ENST00000409069, ENST00000409452, ENST00000409555, ENST00000409759, ENST00000409863, ENST00000415162, ENST00000415952, ENST00000441059, ENST00000459987, ENST00000461835, ENST00000487020, ENST00000898370, ENST00000898371, ENST00000940423, ENST00000940424, ENST00000940425, ENST00000969022

RefSeq mRNA: 4 — MANE Select: NM_015550 NM_015550, NM_145320, NM_145321, NM_145322

CCDS: CCDS47564, CCDS5390, CCDS5391, CCDS5392

Canonical transcript exons

ENST00000313367 — 23 exons

Exon	Start	End
ENSE00000435084	24842279	24842413
ENSE00000832020	24834486	24834736
ENSE00000832021	24840690	24840783
ENSE00000832023	24849069	24849176
ENSE00000832024	24852504	24852634
ENSE00000832025	24861613	24861769
ENSE00000832028	24863496	24863599
ENSE00000832029	24865342	24865465
ENSE00000832030	24871953	24872069
ENSE00000924054	24863200	24863292
ENSE00001212543	24866070	24866237
ENSE00001212549	24870732	24870845
ENSE00001335174	24892377	24892621
ENSE00001839660	24979886	24980178
ENSE00001927895	24796540	24800279
ENSE00003525588	24830768	24830905
ENSE00003549864	24815059	24815203
ENSE00003593715	24816610	24816688
ENSE00003601698	24806776	24806902
ENSE00003624329	24804315	24804437
ENSE00003641708	24809807	24809951
ENSE00003657020	24820175	24820238
ENSE00003786155	24871742	24871795

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 93.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.8925 / max 297.6141, expressed in 1694 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83152	17.4517	1694
83153	0.3017	157
83154	0.1023	34
83151	0.0194	2
83150	0.0174	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	93.59	gold quality
metanephros cortex	UBERON:0010533	92.20	gold quality
amniotic fluid	UBERON:0000173	91.11	gold quality
oocyte	CL:0000023	90.14	gold quality
secondary oocyte	CL:0000655	89.63	gold quality
epithelium of bronchus	UBERON:0002031	89.28	gold quality
bronchus	UBERON:0002185	88.44	gold quality
left lobe of thyroid gland	UBERON:0001120	88.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.16	gold quality
right lobe of thyroid gland	UBERON:0001119	88.13	gold quality
stromal cell of endometrium	CL:0002255	87.77	gold quality
thyroid gland	UBERON:0002046	87.49	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.90	gold quality
skin of abdomen	UBERON:0001416	86.42	gold quality
esophagus mucosa	UBERON:0002469	86.33	gold quality
lower esophagus mucosa	UBERON:0035834	86.15	gold quality
lymph node	UBERON:0000029	86.00	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.87	gold quality
calcaneal tendon	UBERON:0003701	85.72	gold quality
skin of leg	UBERON:0001511	85.65	gold quality
granulocyte	CL:0000094	85.22	gold quality
vagina	UBERON:0000996	84.19	gold quality
gall bladder	UBERON:0002110	84.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.12	gold quality
zone of skin	UBERON:0000014	83.97	gold quality
spleen	UBERON:0002106	83.93	gold quality
right uterine tube	UBERON:0001302	83.75	gold quality
colonic epithelium	UBERON:0000397	83.17	gold quality
rectum	UBERON:0001052	83.02	gold quality
tonsil	UBERON:0002372	82.77	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	50.87
E-ANND-3	yes	12.49
E-GEOD-100618	no	733.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

249 targeting OSBPL3, 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-4262	100.00	73.26	3931
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4795-3P	100.00	74.62	4024
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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790

Literature-anchored findings (GeneRIF, showing 15)

• The intracellular targeting determinants of oxysterol binding protein (OSBP)-related protein 3 (ORP3) were studied using a series of truncated and point mutated constructs. (PMID:16143324)
• The present findings demonstrate a new function of ORP3 as part of the machinery that controls the actin cytoskeleton, cell polarity and cell adhesion. (PMID:18270267)
• phosphorylation of ORP3 controls its association with VAPA. Furthermore, ORP3-VAPA complexes stimulate R-Ras signaling. (PMID:25447204)
• It indicates that VAPB along with ORP3 plays a central role in maintenance of the intracellular PtdIns4P gradient. (PMID:26812496)
• The silencing of VAP-A or ORP3 abrogated the association of Rab7-positive late endosomes with nuclear envelope invaginations and, hence, the transport of endocytosed EV-derived components to the nucleoplasm of recipient cells. (PMID:30018135)
• Aneuploidy-inducing gene knockdowns overlap with cancer mutations and identify Orp3 as a B-cell lymphoma suppressor. (PMID:31659255)
• Calcium-stimulated disassembly of focal adhesions mediated by an ORP3/IQSec1 complex. (PMID:32234213)
• The crystal structure of ORP3 reveals the conservative PI4P binding pattern. (PMID:32819557)
• Downregulation of ORP3 Correlates with Reduced Survival of Colon Cancer Patients with Advanced Nodal Metastasis and of Female Patients with Grade 3 Colon Cancer. (PMID:32824360)
• Structure of human ORP3 ORD reveals conservation of a key function and ligand specificity in OSBP-related proteins. (PMID:33857182)
• Oxysterol binding protein-like 3 (OSBPL3) is a novel driver gene that promotes tumor growth in part through R-Ras/Akt signaling in gastric cancer. (PMID:34584127)
• The relationships of OSBPL3 expression with KI-67 expression and KRAS mutations in CRC: implications for diagnosis and prognosis. (PMID:36517805)
• Oxysterol-binding protein-like 3 is a novel target gene of peroxisome proliferator-activated receptor gamma in fatty liver disease. (PMID:36781118)
• Prognostic and biological function value of OSBPL3 in colorectal cancer analyzed by multi-omic data analysis. (PMID:37550605)
• Loss of ORP3 induces aneuploidy and promotes bladder cancer cell invasion through deregulated microtubule and actin dynamics. (PMID:37740130)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	osbpl3a	ENSDARG00000033251
danio_rerio	osbpl3b	ENSDARG00000040482
mus_musculus	Osbpl3	ENSMUSG00000029822
rattus_norvegicus	Osbpl3	ENSRNOG00000010011

Paralogs (11): OSBPL7 (ENSG00000006025), OSBPL5 (ENSG00000021762), OSBPL6 (ENSG00000079156), OSBPL8 (ENSG00000091039), OSBP (ENSG00000110048), OSBPL9 (ENSG00000117859), OSBPL2 (ENSG00000130703), OSBPL1A (ENSG00000141447), OSBPL10 (ENSG00000144645), OSBPL11 (ENSG00000144909), OSBP2 (ENSG00000184792)

Protein

Protein identifiers

Oxysterol-binding protein-related protein 3 — Q9H4L5 (reviewed: Q9H4L5)

Alternative names: Phosphoinositide transfer protein

All UniProt accessions (4): Q9H4L5, C9J8P4, C9JEF2, C9JZ19

UniProt curated annotations — full annotation on UniProt →

Function. Lipid transfer protein that mediates the non-vesicular transport of phosphoinositide 4-phosphate (1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate), or PI(4)P) at the plasma membrane (PM)/ endoplasmic reticulum (ER) contact sites. Extracts PI4P from the PM, in exchange for phosphatidylcholine. Can bind to the ER membrane protein VAPA and recruit VAPA to PM sites, thus linking these intracellular compartments. The ORP3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface. With VAPA, may regulate ER morphology. Has a role in regulation of the actin cytoskeleton, cell polarity and cell adhesion. Binds to phosphoinositides with preference for PI(3,4)P2 and PI(3,4,5)P3. Also binds 25-hydroxycholesterol and cholesterol.

Subunit / interactions. Homodimer. Interacts with RRAS. Interacts (phosphorylated form) with VAPA. Interacts with OSBPL6.

Subcellular location. Endoplasmic reticulum membrane. Cytoplasm. Cytosol. Cell membrane. Cell projection. Filopodium tip. Nucleus membrane.

Tissue specificity. Expressed in a subset of small lymphocytes (at protein level). Expressed at high concentration in kidney, lymph node and thymus. Expressed at moderate concentration in stomach, jejunum, ileum, appendix, spleen, leukocytes, trachea, lung and thyroid gland. Expressed at low concentration in whole brain, esophagus, duodenum, ileocecum, colon, skeletal muscle, bone marrow, placenta and mammary gland. Isoform 1a, isoform 1b, isoform 1c and isoform 1d are highly expressed in brain, bone marrow, colon, kidney, lung, skeletal muscle, spleen, thymus and thyroid. Not expressed in heart and liver. Isoform 2a, isoform 2b, isoform 2c and isoform 2d are expressed in brain, bone marrow, kidney, skeletal muscle, spleen, thymus and thyroid. Not expressed in heart, liver and lung.

Post-translational modifications. Phosphorylation is enhanced in vitro by phorbol-12-myristate-13-acetate (PMA), forskolin and calcium ionophore A23187. Phosphorylation seems to be stimulated in conditions of low cell-cell (or cell-matrix) adhesion.

Domain organisation. The FFAT 2 motif is required for interaction with VAPA and regulation of the endoplasmic reticulum targeting of ORP3. The FFAT 1 motif may contribute to VAPA binding. The PH domain binds phosphoinositides, with a preference for PI(3,4)P2 and PI(3,4,5)P3. The PH domain mediates targeting to the plasma membrane.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the OSBP family.

Isoforms (8)

UniProt ID	Names	Canonical?
Q9H4L5-1	1a	yes
Q9H4L5-2	1b
Q9H4L5-3	1c
Q9H4L5-4	1d
Q9H4L5-5	2a
Q9H4L5-6	2b
Q9H4L5-7	2c
Q9H4L5-8	2d

RefSeq proteins (4): NP_056365, NP_663160, NP_663161, NP_663162 (=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
IPR041680	PH_8	Domain

Pfam: PF01237, PF15409

Catalyzed reactions (Rhea), 1 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate)(out) + a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate)(in) + a 1,2-diacyl-sn-glycero-3-phosphocholine(out) (RHEA:85491)

UniProt features (77 total): strand 20, helix 16, modified residue 15, mutagenesis site 7, turn 6, splice variant 4, region of interest 2, short sequence motif 2, compositionally biased region 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7CYZ	X-RAY DIFFRACTION	2.1
7DEI	X-RAY DIFFRACTION	2.6
7DEJ	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H4L5-F1	72.93	0.45

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 (15): 200, 251, 265, 304, 309, 320, 323, 371, 372, 410, 425, 437, 440, 16, 34

Mutagenesis-validated functional residues (7):

Position	Phenotype
60	abolishes plasma membrane targeting and nuclear localization.
61	abolishes plasma membrane targeting and nuclear localization.
71	abolishes plasma membrane targeting and nuclear localization.
72	abolishes plasma membrane targeting and nuclear localization.
97	decreases plasma membrane targeting and nuclear localization.
162–167	no effect on interaction with vapa.
451–453	reduces vapa binding. abolishes association with endoplasmic reticulum.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-192105	Synthesis of bile acids and bile salts

MSigDB gene sets: 366 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8_TCELL_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, KANG_FLUOROURACIL_RESISTANCE_UP, LUCAS_HNF4A_TARGETS_UP, CACCAGC_MIR138, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_BILE_ACID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS

GO Biological Process (3): bile acid biosynthetic process (GO:0006699), lipid transport (GO:0006869), sterol transport (GO:0015918)

GO Molecular Function (4): cholesterol binding (GO:0015485), sterol transfer activity (GO:0120015), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (11): endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), nuclear membrane (GO:0031965), filopodium tip (GO:0032433), perinuclear endoplasmic reticulum (GO:0097038), nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Bile acid and bile salt metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
sterol binding	2
binding	2
organelle membrane	2
cytoplasm	2
intracellular membrane-bounded organelle	2
bile acid metabolic process	1
monocarboxylic acid biosynthetic process	1
transport	1
lipid localization	1
lipid transport	1
organic hydroxy compound transport	1
alcohol binding	1
sterol transport	1
lipid transfer activity	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
nucleus	1
nuclear envelope	1
filopodium	1
endoplasmic reticulum	1
perinuclear region of cytoplasm	1
intracellular anatomical structure	1
endomembrane system	1

Protein interactions and networks

STRING

762 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OSBPL3	RRAS	P10301	922
OSBPL3	VAPA	Q9P0L0	747
OSBPL3	PLEK2	Q9NYT0	726
OSBPL3	PLEK	P08567	724
OSBPL3	OSBPL9	Q96SU4	599
OSBPL3	EVA1A	Q9H8M9	500
OSBPL3	OSBP2	Q969R2	476
OSBPL3	ZNF490	Q9ULM2	455
OSBPL3	PJVK	Q0ZLH3	451
OSBPL3	VAPB	O95292	447
OSBPL3	ITPR1	Q14643	432
OSBPL3	NFE2L3	Q9Y4A8	425
OSBPL3	ARHGAP26	Q9UNA1	425
OSBPL3	ENAH	Q8N8S7	425
OSBPL3	PITPNM1	O00562	424
OSBPL3	OPN3	Q9H1Y3	424

IntAct

212 interactions, top by confidence:

A	B	Type	Score
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ACTR3B	ARPC2	psi-mi:“MI:0914”(association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.640
HIF1AN	GMDS	psi-mi:“MI:0914”(association)	0.640
HDAC11	CLUH	psi-mi:“MI:0914”(association)	0.640
ARRDC1	NEDD4	psi-mi:“MI:0914”(association)	0.640
ZFPL1	PPP2R5E	psi-mi:“MI:0914”(association)	0.640
VAPA	PITPNM1	psi-mi:“MI:0914”(association)	0.640
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
TSPYL1	PCM1	psi-mi:“MI:0914”(association)	0.640
TULP3	GGPS1	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
TCEA2	OSBPL3	psi-mi:“MI:0915”(physical association)	0.560
TCEANC	OSBPL3	psi-mi:“MI:0915”(physical association)	0.560
OSBPL3	ZNF835	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	OSBPL3	psi-mi:“MI:0915”(physical association)	0.560
PLK4	OSBPL3	psi-mi:“MI:0915”(physical association)	0.560
FAM161A	OSBPL3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (170): OSBPL3 (Affinity Capture-RNA), OSBPL3 (Affinity Capture-RNA), OSBPL3 (Affinity Capture-MS), OSBPL3 (Affinity Capture-MS), OSBPL3 (Affinity Capture-MS), OSBPL3 (Affinity Capture-MS), OSBPL3 (Affinity Capture-MS), OSBPL3 (Affinity Capture-MS), OSBPL3 (Affinity Capture-MS), OSBPL3 (Affinity Capture-MS), OSBPL3 (Affinity Capture-MS), OSBPL3 (Affinity Capture-MS), OSBPL3 (Affinity Capture-MS), OSBPL3 (Affinity Capture-MS), OSBPL3 (Affinity Capture-MS)

ESM2 similar proteins: A0JPH7, A1A5Q0, B0R034, E1BTG2, E1C065, E1C760, F1MUG2, F7AEX0, G3XA57, O60308, P30306, P48966, Q02225, Q0IID7, Q0VBD2, Q14B46, Q28E45, Q28FA8, Q3UHZ5, Q4KM37, Q5EAW4, Q5FWH3, Q5JTW2, Q5RHY1, Q5XGX5, Q60949, Q6GQN0, Q6INA9, Q6NTY8, Q6NU40, Q6P5Q4, Q7L590, Q80U87, Q8BN58, Q8BXR9, Q8BZN6, Q8C5W4, Q8GT06, Q8K3X6, Q8N8V4

Diamond homologs: A0A2Z4HQ03, A2A8Z1, A8IAD8, O43021, O74178, P0C199, P35843, P35844, P54549, Q02201, Q0IJ05, Q5R9W4, Q96SU4, Q9H4L5, Q9UUA1, Q9UW21, Q9UW25, O13944, O14340, O80866, P16258, P22059, P35845, P38713, Q12451, Q3B7Z2, Q5QNQ6, Q8BX94, Q8BXR9, Q8K4M9, Q8L751, Q8S8P9, Q91XL9, Q93Y40, Q940Y1, Q969R2, Q9BXW6, Q9BZF2, Q9BZF3, Q9DBS9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
OSBPL3	“down-regulates activity”	RRAS	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 175 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
Activation of BAD and translocation to mitochondria	6	40.8×	1e-06
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	36.0×	1e-06
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	36.0×	1e-06
Activation of BH3-only proteins	6	26.6×	6e-06
RHO GTPases activate PKNs	6	17.0×	6e-05
Intrinsic Pathway for Apoptosis	6	15.7×	8e-05
SARS-CoV-1-host interactions	8	12.6×	1e-05
SARS-CoV-1 Infection	9	11.5×	6e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	14.3×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	113
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4425 predictions. Top by Δscore:

Variant	Effect	Δscore
7:24804310:CGAA:C	donor_loss	1.0000
7:24804312:AACCT:A	donor_loss	1.0000
7:24804435:AAC:A	acceptor_gain	1.0000
7:24804436:AC:A	acceptor_gain	1.0000
7:24804437:CC:C	acceptor_gain	1.0000
7:24804438:C:CC	acceptor_gain	1.0000
7:24804444:C:CT	acceptor_gain	1.0000
7:24806770:CCTTA:C	donor_loss	1.0000
7:24806771:CTTA:C	donor_loss	1.0000
7:24806772:TTAC:T	donor_loss	1.0000
7:24806773:TACC:T	donor_loss	1.0000
7:24806774:A:AT	donor_loss	1.0000
7:24806775:C:A	donor_loss	1.0000
7:24806775:CCT:C	donor_gain	1.0000
7:24806901:ATC:A	acceptor_loss	1.0000
7:24806902:TCTA:T	acceptor_loss	1.0000
7:24806903:C:CC	acceptor_gain	1.0000
7:24806904:T:C	acceptor_loss	1.0000
7:24809806:CTTG:C	donor_gain	1.0000
7:24815199:CAAAA:C	acceptor_gain	1.0000
7:24816603:AACTT:A	donor_loss	1.0000
7:24816604:ACTTA:A	donor_loss	1.0000
7:24816605:CTT:C	donor_loss	1.0000
7:24816606:TTACA:T	donor_loss	1.0000
7:24816607:TA:T	donor_loss	1.0000
7:24816608:A:AC	donor_gain	1.0000
7:24816608:A:T	donor_loss	1.0000
7:24816609:C:A	donor_loss	1.0000
7:24816609:C:CC	donor_gain	1.0000
7:24816609:CA:C	donor_gain	1.0000

AlphaMissense

5872 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:24806788:C:A	R811M	1.000
7:24806788:C:G	R811T	1.000
7:24816661:C:T	G659D	1.000
7:24816666:G:C	F657L	1.000
7:24816666:G:T	F657L	1.000
7:24816667:A:G	F657S	1.000
7:24816668:A:G	F657L	1.000
7:24834613:A:T	L540Q	1.000
7:24834622:C:T	G537E	1.000
7:24842327:A:C	F451L	1.000
7:24842327:A:T	F451L	1.000
7:24842329:A:G	F451L	1.000
7:24866176:C:G	R148P	1.000
7:24866197:A:G	L141P	1.000
7:24866210:A:G	W137R	1.000
7:24866210:A:T	W137R	1.000
7:24870736:A:G	L126P	1.000
7:24870740:G:C	H125D	1.000
7:24870763:A:G	L117P	1.000
7:24870769:A:T	I115K	1.000
7:24870794:A:G	S107P	1.000
7:24870811:A:T	V101D	1.000
7:24871762:A:C	Y83D	1.000
7:24871762:A:G	Y83H	1.000
7:24871767:A:G	L81S	1.000
7:24871773:C:T	G79E	1.000
7:24871774:C:G	G79R	1.000
7:24871774:C:T	G79R	1.000
7:24871782:A:G	L76P	1.000
7:24871788:A:G	F74S	1.000

dbSNP variants (sampled 300 via entrez): RS1000005148 (7:24944169 T>A), RS1000009136 (7:24812919 C>T), RS1000012423 (7:24865965 T>C), RS1000032915 (7:24906033 G>T), RS1000056639 (7:24862969 C>A), RS1000071546 (7:24942629 A>C), RS1000082742 (7:24855959 G>A,C), RS1000098256 (7:24897509 T>C), RS1000154927 (7:24822558 C>A,T), RS1000161905 (7:24960917 T>C), RS1000166062 (7:24940294 G>A), RS1000170456 (7:24979750 C>CT), RS1000202578 (7:24983208 T>A), RS1000213676 (7:24920522 T>A,C), RS1000248187 (7:24859552 C>T)

Disease associations

OMIM: gene MIM:606732 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004781_27	Sulfasalazine-induced agranulocytosis	7.000000e-07
GCST005024_105	Pursuit maintenance gain	7.000000e-06
GCST005174_24	Coronary artery calcified atherosclerotic plaque score in type 2 diabetes	1.000000e-06
GCST008103_37	Bipolar disorder	9.000000e-08
GCST009600_137	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	7.000000e-11
GCST012489_112	Heel bone mineral density x serum urate levels interaction	2.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008433	pursuit maintenance gain measurement
EFO:0004723	coronary artery calcification
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066278 (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
6.11	Kd	784.8	nM	CHEMBL3752910
6.02	ED50	946.2	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	2148917: Binding affinity to human OSBPL3 incubated for 45 mins by Kinobead based pull down assay	kd	0.7847	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression, affects methylation	3
bisphenol A	decreases expression, affects cotreatment	2
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Arsenic	decreases expression, increases abundance, increases expression, affects cotreatment	2
Doxorubicin	affects expression, decreases expression	2
Lipopolysaccharides	decreases expression, affects cotreatment	2
Ozone	affects cotreatment, increases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Quercetin	decreases phosphorylation, increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
pirinixic acid	increases activity, affects binding, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	affects expression	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
2-palmitoylglycerol	increases 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
CHEMBL5651959	Binding	Binding affinity to human OSBPL3 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)

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