OSBPL1A

Summary

OSBPL1A (oxysterol binding protein like 1A, HGNC:16398) is a protein-coding gene on chromosome 18q11.2, encoding Oxysterol-binding protein-related protein 1 (Q9BXW6). Binds phospholipids; exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3-phosphate.

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 some members contain only the sterol-binding domain. Transcript variants derived from alternative promoter usage and/or alternative splicing exist; they encode different isoforms.

Source: NCBI Gene 114876 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 128 total
• MANE Select transcript: NM_080597

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16398
Approved symbol	OSBPL1A
Name	oxysterol binding protein like 1A
Location	18q11.2
Locus type	gene with protein product
Status	Approved
Aliases	ORP-1, ORP1
Ensembl gene	ENSG00000141447
Ensembl biotype	protein_coding
OMIM	606730
Entrez	114876

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 8 protein_coding, 5 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000319481, ENST00000357041, ENST00000399441, ENST00000399443, ENST00000578013, ENST00000578055, ENST00000578091, ENST00000579764, ENST00000579851, ENST00000581043, ENST00000581343, ENST00000582350, ENST00000582618, ENST00000582645, ENST00000584119, ENST00000585247, ENST00000880335, ENST00000880336, ENST00000967954

RefSeq mRNA: 3 — MANE Select: NM_080597 NM_001242508, NM_018030, NM_080597

CCDS: CCDS11884, CCDS11885, CCDS56056

Canonical transcript exons

ENST00000319481 — 28 exons

Exon	Start	End
ENSE00000948590	24196125	24196200
ENSE00000948591	24181145	24181279
ENSE00001178659	24165065	24165155
ENSE00001178660	24166579	24166702
ENSE00001178661	24167329	24167445
ENSE00001178667	24170327	24170453
ENSE00001178671	24171409	24171498
ENSE00001178683	24178013	24178195
ENSE00001178687	24179738	24179835
ENSE00001826893	24397655	24397824
ENSE00001939070	24162052	24163281
ENSE00003484505	24314249	24314347
ENSE00003499770	24172376	24172483
ENSE00003503051	24317327	24317400
ENSE00003532769	24332942	24333086
ENSE00003540614	24317149	24317212
ENSE00003570970	24303637	24303718
ENSE00003598842	24225042	24225198
ENSE00003601451	24368287	24368372
ENSE00003609099	24334245	24334330
ENSE00003616550	24239220	24239382
ENSE00003617911	24318748	24318809
ENSE00003636465	24377413	24377535
ENSE00003651259	24311984	24312106
ENSE00003669543	24280842	24280948
ENSE00003679664	24366892	24366966
ENSE00003692464	24318601	24318645
ENSE00003694493	24341547	24341658

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 99.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.1246 / max 513.9151, expressed in 1690 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171405	12.3638	1626
171402	5.6699	1251
171394	3.6574	1078
171390	1.0729	115
171393	1.0209	401
171397	0.4589	196
171396	0.3496	152
171395	0.1778	82
171391	0.1545	57
171398	0.1473	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	99.25	gold quality
medial globus pallidus	UBERON:0002477	99.19	gold quality
globus pallidus	UBERON:0001875	99.11	gold quality
inferior vagus X ganglion	UBERON:0005363	98.99	gold quality
postcentral gyrus	UBERON:0002581	98.68	gold quality
parietal lobe	UBERON:0001872	98.65	gold quality
lateral globus pallidus	UBERON:0002476	98.62	gold quality
subthalamic nucleus	UBERON:0001906	98.34	gold quality
pons	UBERON:0000988	98.33	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.31	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.22	gold quality
occipital lobe	UBERON:0002021	98.18	gold quality
entorhinal cortex	UBERON:0002728	98.12	gold quality
prefrontal cortex	UBERON:0000451	98.08	gold quality
primary visual cortex	UBERON:0002436	98.00	gold quality
substantia nigra pars compacta	UBERON:0001965	97.94	gold quality
superior frontal gyrus	UBERON:0002661	97.92	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.85	gold quality
superior vestibular nucleus	UBERON:0007227	97.79	gold quality
cranial nerve II	UBERON:0000941	97.72	gold quality
ventral tegmental area	UBERON:0002691	97.67	gold quality
pigmented layer of retina	UBERON:0001782	97.62	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.57	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.52	gold quality
spinal cord	UBERON:0002240	97.51	gold quality
frontal cortex	UBERON:0001870	97.44	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.25	gold quality
temporal lobe	UBERON:0001871	97.21	gold quality
middle temporal gyrus	UBERON:0002771	97.13	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

87 targeting OSBPL1A, 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-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-30B-3P	99.70	65.76	2325

Literature-anchored findings (GeneRIF, showing 18)

• Results suggest that the two forms of oxysterol binding protein-related protein-1 (ORP1) are functionally distinct and that ORP1L is involved in control of cellular lipid metabolism (PMID:12631712)
• binds to Rab7, modifies its functional cycle, and can interfere with lysosome organization and endocytic membrane trafficking. (PMID:16176980)
• OSBPL1A was preferentially expressed from the maternal allele (PMID:18369178)
• Results describe how ORP1L contacts VAP to control Rab7-RILP-p150 Glued and late endosome positioning. (PMID:19564404)
• The study shows that OSBPL1A binds several oxysterols and cholesterol, and characterize a mutant, OSBPL1A Delta560-563, defective in oxysterol binding. (PMID:20690035)
• ORP1S is a cytoplasmic sterol sensor, which transports sterols to the nucleus and promotes LXR regulated trans-activation of apoE. (PMID:22728266)
• Data suggest RIDalpha as a model system for understanding physiological egress routes that use ORP1L to activate endosome-to-endoplasmic reticulum (ER) feedback responses involved in lipid droplets (LDs)formation. (PMID:24025716)
• a familial loss-of-function mutation in OSBPL1A affects the first step of the reverse cholesterol transport process and associates with a low HDL-C phenotype (PMID:27105157)
• ORP1L, via its liganding by lipids and the formation of contacts between autophagic vacuoles and the endoplasmic reticulum, governs the last steps in autophagy that lead to the lysosomal degradation of cytosolic material. (PMID:27283760)
• These data suggest that ORP1L is specifically recruited by the bacteria to the Coxiella parasitophorous vacuole, where it influences parasitophorous vacuole membrane dynamics and interactions with the endoplasmic reticulum. (PMID:27345457)
• ORP1L-VAP complexes also support transport of LDL-derived cholesterol from endosomes to the endoplasmic reticulum when ORP1L was bound to human adenovirus RIDalpha. RIDalpha-induced lipid trafficking also attenuated proinflammatory signaling by Toll-like receptor 4, which has a central role in adenovirus pathogenesis and is known to be tightly regulated by cholesterol-rich “lipid rafts.” (PMID:28077646)
• ORP1L-dependent membrane contacts between late endosomes/lysosomes and the endoplasmic reticulum coordinate cholesterol transfer with the retrograde movement of endo-lysosomal vesicles. (PMID:28564600)
• This study validated that rs3746444 polymorphism influenced the expression of miR499a, its target gene, osbpl1a, and thereby associated with the HDL level, which makes it a potential factor involved in the mechanism of atherosclerosis. (PMID:29039586)
• structural and biochemical investigation of the Rab7-ORP1L interaction (PMID:30012887)
• ORP1 is a unique sensor of lysosomal phosphatidylinosito-bisphosphates, and that PI(4,5)P2/PI(3,4)P2 allosterically regulates cholesterol transport by ORP1. (PMID:30783101)
• Oxysterol-binding protein-related protein 1 variants have opposing cholesterol transport activities from the endolysosomes. (PMID:32023146)
• ORP1L mediated PI(4)P signaling at ER-lysosome-mitochondrion three-way contact contributes to mitochondrial division. (PMID:34504082)
• Host Lipid Transport Protein ORP1 Is Necessary for Coxiella burnetii Growth and Vacuole Expansion in Macrophages. (PMID:37017523)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000053746
danio_rerio	osbpl1a	ENSDARG00000105147
mus_musculus	Osbpl1a	ENSMUSG00000044252
rattus_norvegicus	Osbpl1a	ENSRNOG00000054058
drosophila_melanogaster	CG3860	FBGN0034951
caenorhabditis_elegans		WBGENE00008832

Paralogs (11): OSBPL7 (ENSG00000006025), OSBPL5 (ENSG00000021762), OSBPL3 (ENSG00000070882), OSBPL6 (ENSG00000079156), OSBPL8 (ENSG00000091039), OSBP (ENSG00000110048), OSBPL9 (ENSG00000117859), OSBPL2 (ENSG00000130703), OSBPL10 (ENSG00000144645), OSBPL11 (ENSG00000144909), OSBP2 (ENSG00000184792)

Protein

Protein identifiers

Oxysterol-binding protein-related protein 1 — Q9BXW6 (reviewed: Q9BXW6)

All UniProt accessions (10): B0YJ56, E7ER58, Q9BXW6, J3KRT6, J3KSG6, J3KTA6, J3QLA2, J3QS61, J3QSB8, Q6GSK5

UniProt curated annotations — full annotation on UniProt →

Function. Binds phospholipids; exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3-phosphate. Stabilizes GTP-bound RAB7A on late endosomes/lysosomes and alters functional properties of late endocytic compartments via its interaction with RAB7A. Binds 25-hydroxycholesterol and cholesterol.

Subunit / interactions. Interacts (via FFAT motif) with VAPA and VAPB. Interacts with the GTP-bound form of RAB7A. Interacts with OAS1B. Interacts (via FFAT motif) with MOSPD2 (via MSP domain).

Subcellular location. Late endosome.

Domain organisation. The FFAT motif is required for interaction with MOSPD2, VAPA and VAPB.

Similarity. Belongs to the OSBP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BXW6-1	B, OSBPL1B, OSBP8L, ORP1L	yes
Q9BXW6-2	A, OSBPL1A, OSBP8S
Q9BXW6-4	4

RefSeq proteins (3): NP_001229437, NP_060500, NP_542164* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000648	Oxysterol-bd	Family
IPR001849	PH_domain	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR018494	Oxysterol-bd_CS	Conserved_site
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR037239	OSBP_sf	Homologous_superfamily

Pfam: PF01237, PF12796

UniProt features (77 total): helix 25, strand 20, turn 10, region of interest 4, repeat 3, sequence conflict 3, coiled-coil region 2, compositionally biased region 2, splice variant 2, chain 1, short sequence motif 1, modified residue 1, sequence variant 1, mutagenesis site 1, domain 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
6IYB	X-RAY DIFFRACTION	2.09
6TQS	X-RAY DIFFRACTION	2.25
8ZQ3	X-RAY DIFFRACTION	2.43
5ZM5	X-RAY DIFFRACTION	2.6
5ZM6	X-RAY DIFFRACTION	2.7
5ZM7	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXW6-F1	80.85	0.48

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 (1): 499

Mutagenesis-validated functional residues (1):

Position	Phenotype
476–477	loss of interaction with mospd2.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-192105	Synthesis of bile acids and bile salts
R-HSA-2132295	MHC class II antigen presentation

MSigDB gene sets: 227 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, CROONQUIST_NRAS_SIGNALING_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, HUMMERICH_SKIN_CANCER_PROGRESSION_UP, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_BILE_ACID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, VANHARANTA_UTERINE_FIBROID_WITH_7Q_DELETION_DN, CAIRO_HEPATOBLASTOMA_DN, GOZGIT_ESR1_TARGETS_UP, GOBP_MONOCARBOXYLIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (5): bile acid biosynthetic process (GO:0006699), cholesterol metabolic process (GO:0008203), vesicle-mediated transport (GO:0016192), lipid transport (GO:0006869), sterol transport (GO:0015918)

GO Molecular Function (5): phospholipid binding (GO:0005543), cholesterol binding (GO:0015485), sterol transfer activity (GO:0120015), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (8): endosome (GO:0005768), late endosome (GO:0005770), cytosol (GO:0005829), plasma membrane (GO:0005886), organelle membrane contact site (GO:0044232), extracellular exosome (GO:0070062), perinuclear endoplasmic reticulum (GO:0097038), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Bile acid and bile salt metabolism	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
transport	2
sterol binding	2
binding	2
bile acid metabolic process	1
monocarboxylic acid biosynthetic process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
cellular process	1
lipid localization	1
lipid transport	1
organic hydroxy compound transport	1
lipid binding	1
alcohol binding	1
sterol transport	1
lipid transfer activity	1
endomembrane system	1
cytoplasmic vesicle	1
endosome	1
cytoplasm	1
membrane	1
cell periphery	1
organelle	1
extracellular vesicle	1
endoplasmic reticulum	1
perinuclear region of cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

726 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OSBPL1A	RILP	Q96NA2	703
OSBPL1A	VAPA	Q9P0L0	628
OSBPL1A	PLEK	P08567	573
OSBPL1A	PLEK2	Q9NYT0	568
OSBPL1A	STARD3	Q14849	549
OSBPL1A	EXOC1L	A0A1B0GW35	507
OSBPL1A	SYT7	O43581	418
OSBPL1A	RAB7A	P51149	404
OSBPL1A	MOSPD2	Q8NHP6	396
OSBPL1A	STARD3NL	O95772	388
OSBPL1A	NPC1	O15118	379
OSBPL1A	AMPD3	Q01432	374
OSBPL1A	VAPB	O95292	373
OSBPL1A	H1-8	Q8IZA3	358
OSBPL1A	ZFYVE27	Q5T4F4	351

IntAct

72 interactions, top by confidence:

A	B	Type	Score
HEXIM1	CCNT1	psi-mi:“MI:0914”(association)	0.930
INO80E	TFPT	psi-mi:“MI:0914”(association)	0.790
OSBPL1A	VAPB	psi-mi:“MI:0914”(association)	0.760
OSBPL1A	VAPB	psi-mi:“MI:0407”(direct interaction)	0.760
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
OSBPL1A	VAPA	psi-mi:“MI:0407”(direct interaction)	0.700
OSBPL1A	RAB7A	psi-mi:“MI:0407”(direct interaction)	0.670
OSBPL1A	RAB7A	psi-mi:“MI:0915”(physical association)	0.670
OSBPL1A	MOSPD2	psi-mi:“MI:0407”(direct interaction)	0.670
OSBPL1A	MOSPD2	psi-mi:“MI:0915”(physical association)	0.670
OSBPL1A	MOSPD2	psi-mi:“MI:0403”(colocalization)	0.670
HIF1AN	GMDS	psi-mi:“MI:0914”(association)	0.640
CARNMT1	NUP42	psi-mi:“MI:0914”(association)	0.640
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.640
VAPA	PITPNM1	psi-mi:“MI:0914”(association)	0.640
MEOX2	OSBPL1A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (66): OSBPL1A (Affinity Capture-MS), OSBPL1A (Affinity Capture-MS), OSBPL1A (Affinity Capture-MS), OSBPL1A (Affinity Capture-MS), OSBPL1A (Affinity Capture-MS), OSBPL1A (Affinity Capture-MS), OSBPL1A (Affinity Capture-MS), OSBPL1A (Affinity Capture-MS), OSBPL1A (Affinity Capture-MS), OSBPL1A (Affinity Capture-MS), OSBPL1A (Affinity Capture-MS), OSBPL1A (Two-hybrid), OSBPL1A (Affinity Capture-MS), OSBPL1A (Affinity Capture-MS), OSBPL1A (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8QP51, E9PYK3, E9Q4Z2, G1SPE9, O00763, O15228, O23617, P13676, P13798, P19205, P25154, P35574, P80227, P83006, P98192, Q10MJ1, Q2PQH8, Q338C0, Q496Z0, Q5EBA1, Q5IH13, Q5IH14, Q5R5S1, Q5U5V2, Q5ZIB9, Q641Y5, Q6V1X1, Q6YXW6, Q80YA7, Q80YD1, Q80ZK9, Q86TI2, Q8BVG4, Q8C0P5, Q8C5P5, Q8IYB8, Q8K4M9, Q8N5D0, Q8R146, Q8VZF3

Diamond homologs: O13944, O14340, O80866, P16258, P22059, P35845, P38713, Q12451, Q3B7Z2, Q5QNQ6, Q8BX94, Q8BXR9, Q8K4M9, Q8L751, Q8S8P9, Q91XL9, Q93Y40, Q940Y1, Q969R2, Q9BXW6, Q9BZF2, Q9BZF3, Q9DBS9, Q9H1P3, Q9H4L5, Q9LZM1, Q9SAF0, Q9SR33, Q9SU36, D2KC46, D3ZY60, F1MS15, Q02201, Q54ID7, Q54PS9, Q54QP6, Q5M7Y0, Q5R6M6, Q5U3N0, Q6NRZ4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 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.

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase II	7	8.4×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	100
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5742 predictions. Top by Δscore:

Variant	Effect	Δscore
18:24163278:CCAC:C	acceptor_gain	1.0000
18:24163279:CACC:C	acceptor_gain	1.0000
18:24163280:ACCT:A	acceptor_loss	1.0000
18:24163281:CCTGT:C	acceptor_loss	1.0000
18:24163282:C:CA	acceptor_loss	1.0000
18:24165062:CAC:C	donor_loss	1.0000
18:24165063:A:T	donor_loss	1.0000
18:24165151:TTGAT:T	acceptor_gain	1.0000
18:24165152:TGAT:T	acceptor_gain	1.0000
18:24165154:ATCT:A	acceptor_gain	1.0000
18:24165155:TC:T	acceptor_loss	1.0000
18:24165156:C:CC	acceptor_gain	1.0000
18:24165156:CT:C	acceptor_loss	1.0000
18:24165157:T:G	acceptor_loss	1.0000
18:24166578:CCTAT:C	donor_gain	1.0000
18:24166582:T:C	donor_gain	1.0000
18:24166698:TACAT:T	acceptor_gain	1.0000
18:24166700:CAT:C	acceptor_gain	1.0000
18:24166701:ATCTG:A	acceptor_loss	1.0000
18:24166702:TC:T	acceptor_loss	1.0000
18:24166703:C:CA	acceptor_loss	1.0000
18:24166703:C:CC	acceptor_gain	1.0000
18:24166704:T:A	acceptor_loss	1.0000
18:24167323:TCTCA:T	donor_loss	1.0000
18:24167324:CTCAC:C	donor_loss	1.0000
18:24167325:TCAC:T	donor_loss	1.0000
18:24167326:CAC:C	donor_loss	1.0000
18:24167327:A:AT	donor_loss	1.0000
18:24167328:C:T	donor_loss	1.0000
18:24167441:CTCAT:C	acceptor_gain	1.0000

AlphaMissense

6328 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:24170422:A:G	W775R	1.000
18:24170422:A:T	W775R	1.000
18:24172464:A:G	W705R	1.000
18:24172464:A:T	W705R	1.000
18:24178138:A:C	S656R	1.000
18:24178138:A:T	S656R	1.000
18:24178140:T:G	S656R	1.000
18:24179770:G:C	N626K	1.000
18:24179770:G:T	N626K	1.000
18:24181232:G:C	S575R	1.000
18:24181232:G:T	S575R	1.000
18:24181234:T:G	S575R	1.000
18:24165112:T:A	R901S	0.999
18:24165112:T:G	R901S	0.999
18:24165115:T:A	Q900H	0.999
18:24165115:T:G	Q900H	0.999
18:24165128:A:G	L896P	0.999
18:24165131:C:G	R895P	0.999
18:24165136:T:A	K893N	0.999
18:24165136:T:G	K893N	0.999
18:24165137:T:A	K893I	0.999
18:24167364:A:G	W834R	0.999
18:24167364:A:T	W834R	0.999
18:24170427:C:T	G773E	0.999
18:24171433:A:T	V756D	0.999
18:24172416:A:G	W721R	0.999
18:24172416:A:T	W721R	0.999
18:24172424:C:A	G718V	0.999
18:24172425:C:G	G718R	0.999
18:24172430:A:T	I716N	0.999

dbSNP variants (sampled 300 via entrez): RS1000043623 (18:24364837 C>A,G), RS1000045506 (18:24352043 CACA>C), RS1000067602 (18:24308640 T>C,G), RS1000069924 (18:24354215 T>C), RS1000078924 (18:24222741 T>A), RS1000104793 (18:24228132 C>A), RS1000109362 (18:24363293 T>C), RS1000112138 (18:24264643 G>A), RS1000117211 (18:24270968 A>G), RS1000126419 (18:24176611 G>T), RS1000132245 (18:24218123 T>C), RS1000154322 (18:24315049 G>A,C), RS1000177511 (18:24358135 G>A), RS1000177968 (18:24265942 T>C), RS1000180733 (18:24399769 C>T)

Disease associations

OMIM: gene MIM:606730 | 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
GCST000189_26	Protein quantitative trait loci	2.000000e-07
GCST000698_3	Osteoporosis-related phenotypes	4.000000e-07
GCST002593_22	Dementia and core Alzheimer’s disease neuropathologic changes	1.000000e-06
GCST002718_4	Type 2 diabetes	1.000000e-06
GCST90002398_320	Neutrophil count	8.000000e-11
GCST90002407_159	White blood cell count	3.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004696	sex hormone-binding globulin measurement
EFO:0006801	Alzheimer’s disease neuropathologic change
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression, decreases methylation, increases expression	3
Valproic Acid	affects expression, decreases expression	3
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
tetrabromobisphenol A	decreases expression	1
zinc chromate	increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	increases expression, affects cotreatment	1
PCI 5002	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	affects cotreatment, increases expression	1
Cocaine	decreases expression	1

Clinical trials (associated diseases)

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