OSBPL2

Summary

OSBPL2 (oxysterol binding protein like 2, HGNC:15761) is a protein-coding gene on chromosome 20q13.33, encoding Oxysterol-binding protein-related protein 2 (Q9H1P3). Intracellular transport protein that binds sterols and phospholipids and mediates lipid transport between intracellular compartments.

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, although the encoded protein contains only the sterol-binding domain. In vitro studies have shown that the encoded protein can bind strongly to phosphatic acid and weakly to phosphatidylinositol 3-phosphate, but cannot bind to 25-hydroxycholesterol. The protein associates with the Golgi apparatus. Transcript variants encoding different isoforms have been described.

Source: NCBI Gene 9885 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant nonsyndromic hearing loss 67 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 307 total — 7 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 15
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_144498

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15761
Approved symbol	OSBPL2
Name	oxysterol binding protein like 2
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0772, ORP-2, DFNA67
Ensembl gene	ENSG00000130703
Ensembl biotype	protein_coding
OMIM	606731
Entrez	9885

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 27 protein_coding, 7 nonsense_mediated_decay, 3 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000313733, ENST00000358053, ENST00000439951, ENST00000448156, ENST00000471817, ENST00000615516, ENST00000618198, ENST00000618509, ENST00000620616, ENST00000621075, ENST00000622332, ENST00000642516, ENST00000642714, ENST00000642932, ENST00000642957, ENST00000643174, ENST00000643412, ENST00000643981, ENST00000644189, ENST00000644535, ENST00000644702, ENST00000644775, ENST00000645426, ENST00000645442, ENST00000645520, ENST00000645594, ENST00000646834, ENST00000646968, ENST00000865090, ENST00000865091, ENST00000865092, ENST00000865093, ENST00000865094, ENST00000917729, ENST00000917730, ENST00000917731, ENST00000958289, ENST00000958290, ENST00000958291, ENST00000958292

RefSeq mRNA: 4 — MANE Select: NM_144498 NM_001278649, NM_001363878, NM_014835, NM_144498

CCDS: CCDS13494, CCDS13495, CCDS63323, CCDS86966

Canonical transcript exons

ENST00000313733 — 14 exons

Exon	Start	End
ENSE00000897268	62279157	62279339
ENSE00000897274	62281058	62281165
ENSE00000897280	62281790	62281879
ENSE00000897287	62284046	62284169
ENSE00000897294	62286583	62286711
ENSE00000897301	62289207	62289330
ENSE00001211285	62273309	62273406
ENSE00001676330	62259981	62260125
ENSE00003472672	62272125	62272259
ENSE00003491162	62293785	62296183
ENSE00003493699	62256057	62256221
ENSE00003518592	62291703	62291793
ENSE00003541939	62263616	62263691
ENSE00003899498	62238521	62238597

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 96.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.5074 / max 463.0186, expressed in 1813 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185712	13.0901	1779
185711	12.3848	1801
185710	0.0326	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	96.33	gold quality
lower esophagus mucosa	UBERON:0035834	96.29	gold quality
skin of leg	UBERON:0001511	96.03	gold quality
skin of abdomen	UBERON:0001416	95.95	gold quality
body of pancreas	UBERON:0001150	95.30	gold quality
parotid gland	UBERON:0001831	95.22	gold quality
zone of skin	UBERON:0000014	95.13	gold quality
cervix squamous epithelium	UBERON:0006922	95.13	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.06	gold quality
cerebellar hemisphere	UBERON:0002245	94.96	gold quality
cerebellar cortex	UBERON:0002129	94.90	gold quality
buccal mucosa cell	CL:0002336	94.87	gold quality
esophagus mucosa	UBERON:0002469	94.86	gold quality
esophagus squamous epithelium	UBERON:0006920	94.76	gold quality
squamous epithelium	UBERON:0006914	94.71	gold quality
pharyngeal mucosa	UBERON:0000355	94.36	gold quality
cerebellum	UBERON:0002037	94.18	gold quality
blood	UBERON:0000178	94.11	gold quality
gingival epithelium	UBERON:0001949	94.02	gold quality
epithelium of esophagus	UBERON:0001976	93.98	gold quality
gingiva	UBERON:0001828	93.91	gold quality
vagina	UBERON:0000996	93.79	gold quality
tongue squamous epithelium	UBERON:0006919	93.36	gold quality
mammalian vulva	UBERON:0000997	93.28	gold quality
lateral globus pallidus	UBERON:0002476	93.23	gold quality
mouth mucosa	UBERON:0003729	93.16	gold quality
minor salivary gland	UBERON:0001830	93.00	gold quality
saliva-secreting gland	UBERON:0001044	92.96	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	92.95	gold quality
cervix epithelium	UBERON:0004801	92.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting OSBPL2, 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-574-5P	100.00	66.01	989
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
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-371B-5P	99.99	75.34	4759
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 19)

• ORP2 as a novel regulator of cellular sterol homeostasis and intracellular membrane trafficking. (PMID:11861666)
• Results identify ORP2 as a sterol receptor present on LD and provide evidence for its role in the regulation of neutral lipid metabolism, possibly as a factor that integrates the cellular metabolism of triglycerides with that of cholesterol. (PMID:19224871)
• Results identified frameshift and missense mutation in OSBPL2 gene in familial and sporadic case of deafness suggesting OSBPL2 as a novel candidate gene for autosomal dominant nonsyndromic hearing loss . (PMID:25077649)
• Complexes of human ORP2 and VAPs at endoplasmic reticulum-lipid droplet interfaces regulate the hydrolysis of triglycerides and lipid droplet turnover. (PMID:25420878)
• This study and the recent description of another frameshift mutation in a Chinese ADNSHL family identify OSBPL2 as a novel gene for progressive deafness. (PMID:25759012)
• a novel role for ORP2 in regulating steroidogenic capacity and cholesterol homeostasis in the adrenal cortex (PMID:26992564)
• point at a novel function of ORP2 as a lipid-sensing regulator of the actin cytoskeleton, with impacts on hepatocellular migration, adhesion, and proliferation (PMID:29092904)
• this study identifies ORP2 as a new regulatory nexus of Akt signaling, cellular energy metabolism, actin cytoskeletal function, cell migration, and proliferation. (PMID:29947926)
• 25-Hydroxycholesterol down-regulates the expression of OSBPL2 in the HeLa cells. 25-hydroxycholesterol down-regulates OSBPL2 via the p53/SREBP2/NFYA signaling pathway. (PMID:30391516)
• ORP2 regulates the levels of both cholesterol and PI(4,5)P2 on the plasma membrane, and ORP2 forms a tetramer to efficiently transfer PI(4,5)P2. (PMID:30581148)
• data demonstrates that ORP2 binds several phosphoinositides, both PI(4)P and multiply phosphorylated species. ORP2 regulates the subcellular distribution of cholesterol dependent on its PIP-binding capacity. The interaction of ORP2 with ORP1L suggests a concerted action of the two ORPs (PMID:30590084)
• Whole genome sequencing identified a novel pathogenic frameshift mutation, a two-nucleotide deletion, in OSBPL2 (c.158_159delAA) as the pathogenic variant for deafness in a Mongolian family. This finding expands the mutational spectrum of OSBPL2 and contributes to the pathogenic variant list in genetic counseling for deafness screening. (PMID:30894143)
• OSBPL2 deficiency upregulates SQLE expression and increases the accumulation of cholesterol and cholesteryl ester by suppressing AMPK signalling, which provides new evidence of the connection between OSBPL2 and cholesterol synthesis. (PMID:31356817)
• Deletion of OSBPL2 in auditory cells increases cholesterol biosynthesis and drives reactive oxygen species production by inhibiting AMPK activity. (PMID:31427568)
• It identified novel pathways modulated by OSBPL2 orthologues, providing new insight into the mechanism of hearing loss induced by OSBPL2 deficiency. (PMID:31629475)
• ORP2, a cholesterol transporter, regulates angiogenic signaling in endothelial cells. (PMID:32914503)
• Circ-OSBPL2 Contributes to Smoke-Related Chronic Obstructive Pulmonary Disease by Targeting miR-193a-5p/BRD4 Axis. (PMID:33854310)
• ORP2 couples LDL-cholesterol transport to FAK activation by endosomal cholesterol/PI(4,5)P2 exchange. (PMID:34124795)
• OSBPL2 compound heterozygous variants cause dyschromatosis, ichthyosis, deafness and atopic disease syndrome. (PMID:38701954)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	osbpl2b	ENSDARG00000013830
danio_rerio	osbpl2a	ENSDARG00000053804
mus_musculus	Osbpl2	ENSMUSG00000039050
rattus_norvegicus	Osbpl2	ENSRNOG00000057756
drosophila_melanogaster	CG3860	FBGN0034951
caenorhabditis_elegans		WBGENE00008832

Paralogs (11): OSBPL7 (ENSG00000006025), OSBPL5 (ENSG00000021762), OSBPL3 (ENSG00000070882), OSBPL6 (ENSG00000079156), OSBPL8 (ENSG00000091039), OSBP (ENSG00000110048), OSBPL9 (ENSG00000117859), OSBPL1A (ENSG00000141447), OSBPL10 (ENSG00000144645), OSBPL11 (ENSG00000144909), OSBP2 (ENSG00000184792)

Protein

Protein identifiers

Oxysterol-binding protein-related protein 2 — Q9H1P3 (reviewed: Q9H1P3)

All UniProt accessions (18): Q9H1P3, A0A087WTV1, A0A087WVV0, A0A2R8Y362, A0A2R8Y429, A0A2R8Y5B9, A0A2R8Y5R1, A0A2R8Y690, A0A2R8Y703, A0A2R8YD49, A0A2R8YDU7, A0A2R8YEX0, A0A2R8YFT0, A0A2R8YG53, A0A2R8YG59, A0A2R8YG95, E7ET92, H0Y7X4

UniProt curated annotations — full annotation on UniProt →

Function. Intracellular transport protein that binds sterols and phospholipids and mediates lipid transport between intracellular compartments. Increases plasma membrane cholesterol levels and decreases phosphatidylinositol-4,5-bisphosphate levels in the cell membrane. Binds phosphoinositides, such as phosphatidylinositol-4,5-bisphosphate. Exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3-phosphate. Binds cholesterol, dehydroergosterol, 22(R)-hydroxycholesterol and 25-hydroxycholesterol (in vitro).

Subunit / interactions. Monomer. Homotetramer; phosphatidylinositol-4,5-bisphosphate binding promotes formation of stable tetramers. Interacts with DIAPH1.

Subcellular location. Cytoplasm. Cytosol. Lipid droplet. Cell membrane.

Tissue specificity. Widely expressed.

Disease relevance. Deafness, autosomal dominant, 67 (DFNA67) [MIM:616340] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the OSBP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H1P3-1	1	yes
Q9H1P3-2	2

RefSeq proteins (4): NP_001265578, NP_001350807, NP_055650, NP_653081* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000648	Oxysterol-bd	Family
IPR018494	Oxysterol-bd_CS	Conserved_site
IPR037239	OSBP_sf	Homologous_superfamily

Pfam: PF01237

UniProt features (63 total): strand 19, helix 17, mutagenesis site 12, turn 6, binding site 3, modified residue 2, chain 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5ZM8	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H1P3-F1	83.92	0.68

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 (3): 90; 178–179; 427–431

Post-translational modifications (2): 19, 20

Mutagenesis-validated functional residues (12):

Position	Phenotype
83	no effect on phosphatidylinositide binding, but impaired tetramerization and decreased cholesterol binding, plus decreas
87–90	loss of the ability to promote cholesterol accumulation at the cell membrane. no effect on phosphatidylinositide levels
93	mildly decreased 25-hydroxycholesterol binding.
103	mildly decreased 25-hydroxycholesterol binding.
110	no effect on phosphatidylinositide binding, but decreased cholesterol binding, plus decreased cholesterol and phosphatid
150	reduces 25-hydroxycholesterol binding.
152	does not significantly impair 25-hydroxycholesterol binding.
178–179	loss of increased cholesterol and decreased phosphatidylinositide accumulation at the cell membrane.
215	no effect on phosphatidylinositide binding, but decreased cholesterol binding, plus decreased cholesterol and phosphatid
249	reduces 25-hydroxycholesterol binding. loss of 22(r)-hydroxycholesterol binding.
423	loss of increased cholesterol and decreased phosphatidylinositide accumulation at the cell membrane.
79	no effect on phosphatidylinositide binding, but impaired tetramerization and decreased cholesterol binding, plus decreas

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 239 (showing top): GCM_GSPT1, GOBP_PROTEIN_HOMOTETRAMERIZATION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOBP_BILE_ACID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_EXOCYTOSIS, MODULE_480

GO Biological Process (11): bile acid biosynthetic process (GO:0006699), plasma membrane organization (GO:0007009), regulation of synaptic vesicle priming (GO:0010807), phospholipid transport (GO:0015914), cholesterol transport (GO:0030301), intracellular cholesterol transport (GO:0032367), protein homotetramerization (GO:0051289), regulation of presynaptic cytosolic calcium ion concentration (GO:0099509), lipid transport (GO:0006869), sterol transport (GO:0015918), intermembrane lipid transfer (GO:0120009)

GO Molecular Function (7): phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), phosphatidylinositol transfer activity (GO:0008526), cholesterol binding (GO:0015485), sterol transfer activity (GO:0120015), cholesterol transfer activity (GO:0120020), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (9): lipid droplet (GO:0005811), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic side of plasma membrane (GO:0009898), perinuclear endoplasmic reticulum (GO:0097038), presynaptic active zone cytoplasmic component (GO:0098831), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), membrane (GO:0016020)

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	4
lipid transport	3
membrane organization	2
sterol transport	2
intracellular anatomical structure	2
lipid transfer activity	2
sterol binding	2
binding	2
bile acid metabolic process	1
monocarboxylic acid biosynthetic process	1
endomembrane system organization	1
synaptic vesicle priming	1
regulation of protein-containing complex assembly	1
organophosphate ester transport	1
cholesterol transport	1
intracellular sterol transport	1
protein homooligomerization	1
protein tetramerization	1
regulation of cytosolic calcium ion concentration	1
neuron cellular homeostasis	1
presynapse	1
transport	1
lipid localization	1
organic hydroxy compound transport	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
phosphatidylinositol binding	1
alcohol binding	1
cholesterol binding	1
sterol transfer activity	1
intracellular membraneless organelle	1
cytoplasm	1
membrane	1
cell periphery	1
plasma membrane	1
cytoplasmic side of membrane	1
endoplasmic reticulum	1
perinuclear region of cytoplasm	1
presynaptic active zone	1
cell cortex region	1

Protein interactions and networks

STRING

840 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OSBPL2	PLEK2	Q9NYT0	668
OSBPL2	PLEK	P08567	666
OSBPL2	LAMA5	O15230	550
OSBPL2	PLPP7	Q8NBV4	509
OSBPL2	SS18L1	O75177	495
OSBPL2	ANK1	P16157	489
OSBPL2	VAPA	Q9P0L0	489
OSBPL2	ANK3	Q12955	478
OSBPL2	ANK2	Q01484	475
OSBPL2	SLCO6A1	Q86UG4	475
OSBPL2	H1-8	Q8IZA3	470
OSBPL2	DEGS2	Q6QHC5	463
OSBPL2	STARD3	Q14849	454
OSBPL2	ITPRIP	Q8IWB1	446
OSBPL2	NPC1	O15118	444

IntAct

25 interactions, top by confidence:

A	B	Type	Score
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
OSBPL2	VAPA	psi-mi:“MI:0915”(physical association)	0.660
OSBPL2	VAPB	psi-mi:“MI:0915”(physical association)	0.660
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.640
VAPA	PITPNM1	psi-mi:“MI:0914”(association)	0.640
OSBPL2	VAPB	psi-mi:“MI:0915”(physical association)	0.560
VAPB	OSBPL2	psi-mi:“MI:0915”(physical association)	0.560
SNRPF	OSBPL2	psi-mi:“MI:0915”(physical association)	0.560
VTN	HAT1	psi-mi:“MI:0914”(association)	0.530
OSBPL2	BIRC6	psi-mi:“MI:0915”(physical association)	0.500
OSBPL2	MAP1LC3B	psi-mi:“MI:0915”(physical association)	0.400
rep	TMEM120B	psi-mi:“MI:0914”(association)	0.350
APBB2	APBB1	psi-mi:“MI:0914”(association)	0.350
OSBPL2	ZFPL1	psi-mi:“MI:0914”(association)	0.350
FAXC	HAT1	psi-mi:“MI:0914”(association)	0.350
EPHA8	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
OSBPL2	SNRPF	psi-mi:“MI:0915”(physical association)	0.000
	OSBPL2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (58): OSBPL2 (Two-hybrid), OSBPL2 (Affinity Capture-MS), OSBPL2 (Affinity Capture-MS), OSBPL2 (Affinity Capture-MS), OSBPL2 (Affinity Capture-MS), OSBPL2 (Affinity Capture-MS), OSBPL2 (Affinity Capture-MS), OSBPL2 (Affinity Capture-MS), OSBPL2 (Affinity Capture-MS), OSBPL2 (Affinity Capture-MS), OSBPL2 (Affinity Capture-MS), OSBPL2 (Affinity Capture-MS), ZFPL1 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), OSBPL2 (Proximity Label-MS)

ESM2 similar proteins: A2A2Y4, A2AFR3, A6NI28, A7E300, B2RQE8, B9EJ86, E9Q5G3, G9CGD6, O14795, P0CAX5, Q0P4Q4, Q3KR37, Q4KUS2, Q58A65, Q5JSJ4, Q5M7R9, Q5QNQ6, Q5R803, Q62768, Q62769, Q69ZT9, Q6ISB3, Q6PCS4, Q80TI0, Q80YA9, Q8BHD4, Q8BND4, Q8BX94, Q8CI95, Q8K4M9, Q8K5C0, Q8L751, Q8WXI2, Q91XL9, Q940Y1, Q969R2, Q96QF0, Q99J31, Q9BXB4, Q9BXB5

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	1
Uncertain significance	107
Likely benign	113
Benign	51

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
190110	NM_144498.4(OSBPL2):c.156_157del (p.Gln53fs)	Pathogenic
190111	NM_144498.4(OSBPL2):c.141_142del (p.Arg50fs)	Pathogenic
4526564	OSBPL2, 10-BP DEL, NT1443+1, 3-PRIME UTR	Pathogenic
4526565	OSBPL2, IVS1, G-C, -1	Pathogenic
4804294	NM_144498.4(OSBPL2):c.478dup (p.Tyr160fs)	Pathogenic
977817	NM_144498.4(OSBPL2):c.180_181del (p.His60fs)	Pathogenic
987443	NM_144498.4(OSBPL2):c.158_159del (p.Gln53fs)	Pathogenic
4293257	NM_144498.4(OSBPL2):c.160_164del (p.Glu54fs)	Likely pathogenic

SpliceAI

3304 predictions. Top by Δscore:

Variant	Effect	Δscore
20:62238594:CCAGG:C	donor_loss	1.0000
20:62238595:CAGG:C	donor_loss	1.0000
20:62238596:AGGTG:A	donor_loss	1.0000
20:62238598:GTG:G	donor_loss	1.0000
20:62238599:T:G	donor_loss	1.0000
20:62242430:TGG:T	donor_gain	1.0000
20:62242432:G:GT	donor_gain	1.0000
20:62263614:A:AG	acceptor_gain	1.0000
20:62263615:G:GG	acceptor_gain	1.0000
20:62263615:GGAC:G	acceptor_gain	1.0000
20:62263687:GCCTG:G	donor_gain	1.0000
20:62263688:CCTGG:C	donor_loss	1.0000
20:62263689:CTGG:C	donor_loss	1.0000
20:62263690:TGG:T	donor_loss	1.0000
20:62263691:GGT:G	donor_loss	1.0000
20:62263692:G:GC	donor_loss	1.0000
20:62263692:G:GG	donor_gain	1.0000
20:62263693:TGA:T	donor_loss	1.0000
20:62263694:GAG:G	donor_loss	1.0000
20:62272124:GGA:G	acceptor_gain	1.0000
20:62272190:G:GT	donor_gain	1.0000
20:62272253:G:GT	donor_gain	1.0000
20:62273307:A:AG	acceptor_gain	1.0000
20:62273308:G:GG	acceptor_gain	1.0000
20:62279340:G:GG	donor_gain	1.0000
20:62281053:CACA:C	acceptor_loss	1.0000
20:62281054:ACAG:A	acceptor_loss	1.0000
20:62281056:A:AG	acceptor_gain	1.0000
20:62281056:A:G	acceptor_loss	1.0000
20:62281057:G:GT	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000048404 (20:62242533 G>A,T), RS1000064681 (20:62266493 G>A,C,T), RS1000079185 (20:62242223 G>A), RS1000176968 (20:62286951 C>T), RS1000187155 (20:62273600 C>T), RS1000329337 (20:62262446 G>A), RS1000343625 (20:62254503 G>T), RS1000385698 (20:62289503 G>A), RS1000388870 (20:62292079 C>G,T), RS1000412435 (20:62254326 C>T), RS1000463079 (20:62279506 C>A), RS1000520732 (20:62288186 G>C), RS1000620175 (20:62237685 A>G), RS1000676656 (20:62255850 G>C), RS1000778313 (20:62269409 C>A,G)

Disease associations

OMIM: gene MIM:606731 | disease phenotypes: MIM:616340, MIM:621400

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant nonsyndromic hearing loss 67	Strong	Autosomal dominant
nonsyndromic genetic hearing loss	Moderate	Autosomal dominant
autosomal dominant nonsyndromic hearing loss	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Moderate	AD

Mondo (4): autosomal dominant nonsyndromic hearing loss 67 (MONDO:0014594), dyschromatosis, ichthyosis, deafness, and atopic disease (MONDO:0980712), nonsyndromic genetic hearing loss (MONDO:0019497), autosomal dominant nonsyndromic hearing loss (MONDO:0019587)

Orphanet (1): Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635)

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000360	Tinnitus
HP:0000407	Sensorineural hearing impairment
HP:0000836	Hyperthyroidism
HP:0000962	Hyperkeratosis
HP:0000964	Eczematoid dermatitis
HP:0001047	Atopic dermatitis
HP:0002099	Asthma
HP:0002257	Chronic rhinitis
HP:0003621	Juvenile onset
HP:0007380	Facial telangiectasia
HP:0007440	Generalized hyperpigmentation
HP:0008064	Ichthyosis
HP:0020073	Hypopigmented macule

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001942_4	Prostate cancer	4.000000e-08
GCST005795_11	Femoral neck bone mineral density	8.000000e-06
GCST005796_34	Lumbar spine bone mineral density	2.000000e-08
GCST008058_250	Estimated glomerular filtration rate	4.000000e-13
GCST010105_51	Nicotine dependence symptom count	4.000000e-06
GCST012465_14	Bipolar disorder	9.000000e-09
GCST90002385_570	High light scatter reticulocyte count	1.000000e-16
GCST90002386_525	High light scatter reticulocyte percentage of red cells	1.000000e-17
GCST90002405_408	Reticulocyte count	2.000000e-17
GCST90002406_561	Reticulocyte fraction of red cells	5.000000e-19

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007785	femoral neck bone mineral density
EFO:0007701	spine bone mineral density
EFO:0009262	nicotine dependence symptom count
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C580334	Nonsyndromic Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
bisphenol A	decreases expression, decreases methylation	2
Cyclosporine	increases expression	2
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
tetrabromobisphenol A	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
methacrylaldehyde	decreases expression, increases abundance, affects cotreatment	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Bortezomib	increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Acrolein	decreases expression, increases abundance, affects cotreatment	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Atrazine	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	affects expression	1
Coumestrol	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations