OPCML

Summary

OPCML (opioid binding protein/cell adhesion molecule like, HGNC:8143) is a protein-coding gene on chromosome 11q25, encoding Opioid-binding protein/cell adhesion molecule (Q14982). Binds opioids in the presence of acidic lipids; probably involved in cell contact.

This gene encodes a member of the IgLON subfamily in the immunoglobulin protein superfamily of proteins. The encoded preprotein is proteolytically processed to generate the mature protein. This protein is localized in the plasma membrane and may have an accessory role in opioid receptor function. This gene has an ortholog in rat and bovine. The opioid binding-cell adhesion molecule encoded by the rat gene binds opioid alkaloids in the presence of acidic lipids, exhibits selectivity for mu ligands and acts as a GPI-anchored protein. Since the encoded protein is highly conserved in species during evolution, it may have a fundamental role in mammalian systems. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed.

Source: NCBI Gene 4978 — RefSeq curated summary.

At a glance

• GWAS associations: 33
• Clinical variants (ClinVar): 56 total — 2 pathogenic
• Phenotypes (HPO): 5
• MANE Select transcript: NM_001012393

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8143
Approved symbol	OPCML
Name	opioid binding protein/cell adhesion molecule like
Location	11q25
Locus type	gene with protein product
Status	Approved
Aliases	OPCM, OBCAM, IGLON1
Ensembl gene	ENSG00000183715
Ensembl biotype	protein_coding
OMIM	600632
Entrez	4978

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000331898, ENST00000374778, ENST00000524381, ENST00000525412, ENST00000529019, ENST00000529038, ENST00000541867

RefSeq mRNA: 6 — MANE Select: NM_001012393 NM_001012393, NM_001319103, NM_001319104, NM_001319105, NM_001319106, NM_002545

CCDS: CCDS31722, CCDS81649, CCDS8492

Canonical transcript exons

ENST00000524381 — 8 exons

Exon	Start	End
ENSE00002140877	132414981	132420293
ENSE00002185919	133532264	133532501
ENSE00003479898	132436659	132436779
ENSE00003507147	132436086	132436237
ENSE00003542746	132942926	132943010
ENSE00003561753	132437222	132437359
ENSE00003613345	132529061	132529186
ENSE00003630161	132657087	132657319

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 99.62.

FANTOM5 (CAGE): breadth broad, TPM avg 6.8268 / max 325.0659, expressed in 387 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123229	3.4017	185
123208	0.6725	189
123228	0.6634	120
123232	0.4672	89
123233	0.2358	69
123234	0.2189	78
123231	0.1639	59
123230	0.1538	54
123194	0.1205	57
123203	0.1064	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	99.62	gold quality
middle temporal gyrus	UBERON:0002771	99.18	gold quality
endothelial cell	CL:0000115	98.65	gold quality
pigmented layer of retina	UBERON:0001782	98.39	gold quality
orbitofrontal cortex	UBERON:0004167	98.25	gold quality
postcentral gyrus	UBERON:0002581	97.63	gold quality
superior frontal gyrus	UBERON:0002661	97.61	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.40	gold quality
cortical plate	UBERON:0005343	97.38	gold quality
entorhinal cortex	UBERON:0002728	97.29	gold quality
parietal lobe	UBERON:0001872	97.21	gold quality
CA1 field of hippocampus	UBERON:0003881	97.14	gold quality
cerebellar vermis	UBERON:0004720	96.40	gold quality
buccal mucosa cell	CL:0002336	96.12	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.99	gold quality
primary visual cortex	UBERON:0002436	95.29	gold quality
occipital lobe	UBERON:0002021	94.74	gold quality
frontal pole	UBERON:0002795	93.90	gold quality
paraflocculus	UBERON:0005351	93.82	gold quality
cerebellum	UBERON:0002037	92.70	gold quality
Brodmann (1909) area 10	UBERON:0013541	92.53	gold quality
prefrontal cortex	UBERON:0000451	92.50	gold quality
cerebellar cortex	UBERON:0002129	92.15	gold quality
cerebellar hemisphere	UBERON:0002245	92.05	gold quality
frontal cortex	UBERON:0001870	92.00	gold quality
cerebral cortex	UBERON:0000956	91.62	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.57	gold quality
neocortex	UBERON:0001950	91.33	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.25	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	5356.54
E-HCAD-35	yes	87.50
E-HCAD-25	yes	75.76
E-GEOD-84465	yes	23.38
E-ANND-3	yes	5.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

195 targeting OPCML, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3119	99.92	71.34	2390

Literature-anchored findings (GeneRIF, showing 28)

• OPCML at 11q25 is epigenetically inactivated and has tumor-suppressor function in epithelial ovarian cancer (PMID:12819783)
• Oncogenic RAS activity is directly responsible for the observed OPCML promoter hypermethylation and epigenetic gene silencing of OPCML. (PMID:16384911)
• The results were confirmed at the level of mRNA and protein, and suggested that four genes (OPCML, RNASE1, YES1 and ACK1) could play a key role in the tumorigenesis and metastasis of gastric cancer. (PMID:17109515)
• Hypermethylation of OPCML gene is responsible for silencing and loss of suppressor function in ovarian cancer. (PMID:17159813)
• OPCML down-regulation occurs in the majority of brain tumours tested (PMID:17239010)
• Results identified OPCML loci showing significant differential DNA methylation levels between tumor and non-tumor lung and highly significant hypermethylation in adenocarcinoma. (PMID:17967182)
• loss of OPCML expression occurs frequently in ovarian serous carcinoma. CpG island methylation and LOH are probably two mechanisms of OPCML inactivation (PMID:18179137)
• OPCML gene promoter methylation may play an important role in the carcinogenesis of cervical carcinoma. OPCML may be a cervical carcinoma-associated candidate tumor suppressor gene. (PMID:18584347)
• OPCML is a broad tumor suppressor, which is frequently inactivated by methylation in multiple malignancies. (PMID:18714356)
• opioid binding protein/cell adhesion molecule-like promoter methylation has a role in bladder carcinoma (PMID:21273058)
• A strong association was found between an intronic SNP of the OPCML gene (rs1784519) and the risk of schizophrenia in the Thai population (PMID:21833655)
• The OPCML tumor suppressor negatively regulates a specific spectrum of receptor tyrosine kinases in ovarian cancer cells by binding to their extracellular domain. (PMID:22585860)
• The generation and cardiac phenotype of single and double heterozygous gene-targeted OPCML and Neurotrimin knockout mice. (PMID:24616287)
• Detection of OPCML hypermethylation in the serum is useful for diagnosis of ovarian carcinoma. (PMID:24839818)
• the DNA methylation levels of OPCML and SFRP1 could be potential biomarkers for diagnosis of CCA with high specificity, sensitivity, and accuracy, in particular for biopsy specimens (PMID:25652468)
• OPCML and FLRT2 were further validated in an independent cohort consisting of 20 low-Gleason and 33 high-Gleason tissues. We then compared patients with biochemical recurrence (n=70) vs. those without (n=86) in a third cohort, and they showed no difference in methylation at these DMR loci (PMID:26890304)
• OPCML plays an important role in gastric cancer, and may be a new prognostic indicator of gastric cancer. (PMID:27358143)
• Study revealed that reduced expression of OPCML might have a significant correlation with unfavorable tumor stage and differentiation, predict poor prognosis of patients with gastric cancer. OPCML had a tumor-suppressing activity possibly via AKT/GSK3beta signaling in gastric cancer. (PMID:28407749)
• Here we show that, though OPCML interacts only with HER2 and not with EGFR, the interaction of OPCML with HER2 disrupts the formation of the HER2-EGFR heterodimer, and this translates into a better response to both lapatinib and erlotinib in HER2-expressing ovarian and breast cancer cell lines (PMID:28775148)
• OPCML and PTPRG, coordinate to repress AXL-dependent oncogenic signalling. (PMID:29907679)
• OPCML promoter was found to be hypermethylated in esophageal squamous cell carcinoma (ESCC) samples. Hypermethylation of the studied OPCML promoter produced no effect on OPCML protein expression in Grade 2 tumors but revealed downregulation in Grade 3 tumors. Deranged OPCML expression may lead to high-grade ESCC as well as epigenetically regulated genes that may alter the Wnt/beta-catenin and TGF-beta-Smad pathways in … (PMID:30880778)
• Human opioid-binding protein/cell adhesion molecule (OPCML) is expressed in many tissues and localizes to the plasma membrane. It is a putative tumor suppressor that acts on receptor tyrosine kinases, influencing cell cycle arrest, apoptosis, and migration. Its expression is silenced epigenetically in cancer, inferring potential diagnostic, prognostic, and therapeutic roles. [Review] (PMID:31421903)
• The Schizophrenia Susceptibility Gene OPCML Regulates Spine Maturation and Cognitive Behaviors through Eph-Cofilin Signaling. (PMID:31577955)
• LINC00619 restricts gastric cancer progression by preventing microRNA-224-5p-mediated inhibition of OPCML. (PMID:32359894)
• Emerging roles for the GPI-anchored tumor suppressor OPCML in cancers. (PMID:32595215)
• Expression and promoter methylation status of OPCML and its functions in the inhibition of cell proliferation, migration, and invasion in breast cancer. (PMID:33108608)
• OPCML Exerts Antitumor Effects in Cholangiocarcinoma via AXL/STAT3 Inactivation and Rho GTPase Down-regulation. (PMID:34697068)
• Combined OPCML and AXL Expression as a Prognostic Marker and OPCML Enhances AXL Inhibitor in Cholangiocarcinoma. (PMID:35478117)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	ntm	ENSDARG00000018065
mus_musculus	Opcml	ENSMUSG00000062257
rattus_norvegicus	Opcml	ENSRNOG00000023809
drosophila_melanogaster	Ama	FBGN0000071
drosophila_melanogaster	Lac	FBGN0010238
drosophila_melanogaster	klg	FBGN0017590
drosophila_melanogaster	fipi	FBGN0031627
drosophila_melanogaster	DIP-eta	FBGN0031725
drosophila_melanogaster	DIP-iota	FBGN0031837
drosophila_melanogaster	CG13506	FBGN0034723
drosophila_melanogaster	DIP-zeta	FBGN0051708
drosophila_melanogaster	DIP-kappa	FBGN0051814
drosophila_melanogaster	CG33543	FBGN0053543
drosophila_melanogaster	DIP-beta	FBGN0259245
drosophila_melanogaster	DIP-epsilon	FBGN0259714
caenorhabditis_elegans	rig-5	WBGENE00004372

Paralogs (5): IGLON5 (ENSG00000142549), NEGR1 (ENSG00000172260), NTM (ENSG00000182667), IGSF5 (ENSG00000183067), LSAMP (ENSG00000185565)

Protein

Protein identifiers

Opioid-binding protein/cell adhesion molecule — Q14982 (reviewed: Q14982)

Alternative names: IgLON family member 1

All UniProt accessions (2): A8K0Y0, Q14982

UniProt curated annotations — full annotation on UniProt →

Function. Binds opioids in the presence of acidic lipids; probably involved in cell contact.

Subcellular location. Cell membrane.

Disease relevance. Ovarian cancer (OC) [MIM:167000] The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Similarity. Belongs to the immunoglobulin superfamily. IgLON family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q14982-1	1	yes
Q14982-2	2
Q14982-3	3
Q14982-4	4

RefSeq proteins (6): NP_001012393, NP_001306032, NP_001306033, NP_001306034, NP_001306035, NP_002536 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050876	IgLON_domain	Family

Pfam: PF07679, PF13927

UniProt features (44 total): strand 21, glycosylation site 6, disulfide bond 3, splice variant 3, domain 3, helix 2, signal peptide 1, chain 1, sequence variant 1, propeptide 1, turn 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5UV6	X-RAY DIFFRACTION	2.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14982-F1	83.55	0.70

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): 322

Disulfide bonds (3): 57–115, 157–202, 244–296

Glycosylation sites (6): 285, 293, 306, 44, 70, 140

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins

MSigDB gene sets: 176 (showing top): MORF_ITGA2, ACTACCT_MIR196A_MIR196B, GOBP_NEURON_RECOGNITION, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_SYNAPSE_ASSEMBLY, FISCHER_G1_S_CELL_CYCLE, GCANCTGNY_MYOD_Q6, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, CAGCTG_AP4_Q5, MORF_RAD51L3, GOBP_CELL_CELL_ADHESION, NFKB_C

GO Biological Process (2): cell adhesion (GO:0007155), neuron recognition (GO:0008038)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), plasma membrane (GO:0005886), side of membrane (GO:0098552), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
membrane	2
cellular process	1
cell recognition	1
neuron development	1
binding	1
cell periphery	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

2448 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OPCML	RYR3	Q15413	723
OPCML	SORL1	Q92673	586
OPCML	FHIT	P49789	552
OPCML	RASSF1	Q9NS23	544
OPCML	RRAS2	P17082	542
OPCML	CNTN2	P78432	474
OPCML	WWOX	Q9NZC7	474
OPCML	CDH13	P55290	469
OPCML	ADGRL3	Q9HAR2	466
OPCML	ADGRB3	O60242	452
OPCML	MSH3	P20585	442
OPCML	GABRA5	P31644	432
OPCML	PDE4D	Q08499	431
OPCML	NTMT2	Q5VVY1	429
OPCML	GRM8	O00222	427

IntAct

25 interactions, top by confidence:

A	B	Type	Score
KRTAP10-8	OPCML	psi-mi:“MI:0915”(physical association)	0.560
OPCML	KRTAP5-2	psi-mi:“MI:0915”(physical association)	0.560
OPCML	NUP93	psi-mi:“MI:0915”(physical association)	0.560
OPCML	CANX	psi-mi:“MI:0914”(association)	0.530
OPCML	TIMM44	psi-mi:“MI:0915”(physical association)	0.400
OPCML	NEGR1	psi-mi:“MI:0915”(physical association)	0.400
OPCML	OPCML	psi-mi:“MI:0915”(physical association)	0.400
ECE1	OPCML	psi-mi:“MI:0915”(physical association)	0.370
ATXN1	OPCML	psi-mi:“MI:0915”(physical association)	0.370
OPCML	HLA-A	psi-mi:“MI:0914”(association)	0.350
NTM	CALR	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
YTHDF1	H1-1	psi-mi:“MI:0914”(association)	0.350
HTT	TPP1	psi-mi:“MI:0914”(association)	0.350
OPCML	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.000
OPCML	KRTAP5-2	psi-mi:“MI:0915”(physical association)	0.000
OPCML	NUP93	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (29): KRT40 (Two-hybrid), KRTAP10-3 (Two-hybrid), OPCML (Affinity Capture-MS), OPCML (Affinity Capture-MS), MBLAC2 (Affinity Capture-MS), TRIP12 (Affinity Capture-MS), TMEM214 (Affinity Capture-MS), CANX (Affinity Capture-MS), NCAM1 (Affinity Capture-MS), FBXO2 (Affinity Capture-MS), OPCML (Affinity Capture-Western), EPHA2 (Affinity Capture-Western), OPCML (Affinity Capture-Western), ERBB2 (Affinity Capture-Western), FGFR1 (Affinity Capture-Western)

ESM2 similar proteins: A4IFA6, A6NGN9, B1AUH1, B3N666, B4Q599, O09127, O73791, P00545, P07333, P11834, P13369, P29322, P32736, P35590, P35916, P35917, Q06805, Q06806, Q13308, Q13449, Q14982, Q2EY13, Q2EY14, Q2EY15, Q2VWP9, Q58DA5, Q5IS61, Q5JZY3, Q5R412, Q62718, Q62813, Q6GU68, Q7Z3B1, Q80Z24, Q8BKG3, Q8BLK3, Q8BYG9, Q8HW98, Q8TDY8, Q90773

Diamond homologs: A2A8L5, A4IFW2, A6NGN9, A7MBJ4, B3N666, B4GBH0, B4GKZ8, B4HY03, B4KPU0, B4NZY8, B4Q599, P10586, P11834, P32736, Q03696, Q0E9H9, Q13449, Q14982, Q24372, Q26474, Q290N5, Q29JX6, Q58DA5, Q5IS61, Q5R412, Q62718, Q62813, Q64604, Q696W0, Q7Z3B1, Q80Z24, Q8BLK3, Q8HW98, Q90773, Q98892, Q98919, Q99PJ0, Q9P121, Q9VM64, Q9W6V2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	42
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
563872	GRCh37/hg19 11q25(chr11:132187876-134938470)x1	Pathogenic
8983	NM_001012393.5(OPCML):c.263C>G (p.Pro88Arg)	Pathogenic

SpliceAI

4550 predictions. Top by Δscore:

Variant	Effect	Δscore
11:132436079:CACT:C	donor_loss	1.0000
11:132436080:ACTC:A	donor_loss	1.0000
11:132436081:CT:C	donor_loss	1.0000
11:132436082:TCACC:T	donor_loss	1.0000
11:132436083:CA:C	donor_loss	1.0000
11:132436084:A:AC	donor_gain	1.0000
11:132436084:A:C	donor_loss	1.0000
11:132436085:C:CA	donor_loss	1.0000
11:132436085:C:CC	donor_gain	1.0000
11:132436085:CCATA:C	donor_gain	1.0000
11:132436233:CTAAC:C	acceptor_gain	1.0000
11:132436234:TAAC:T	acceptor_gain	1.0000
11:132436238:C:CC	acceptor_gain	1.0000
11:132436238:CTGCA:C	acceptor_loss	1.0000
11:132437217:CTCA:C	donor_loss	1.0000
11:132437218:TCACA:T	donor_loss	1.0000
11:132437219:CACAG:C	donor_loss	1.0000
11:132437220:A:AC	donor_gain	1.0000
11:132437220:ACA:A	donor_loss	1.0000
11:132437221:C:CA	donor_loss	1.0000
11:132437221:C:CC	donor_gain	1.0000
11:132437239:A:AC	donor_gain	1.0000
11:132437240:C:CC	donor_gain	1.0000
11:132437243:T:A	donor_gain	1.0000
11:132437355:GCCTT:G	acceptor_gain	1.0000
11:132437356:CCTTC:C	acceptor_gain	1.0000
11:132437357:CTT:C	acceptor_gain	1.0000
11:132437359:TCT:T	acceptor_loss	1.0000
11:132437360:C:CC	acceptor_gain	1.0000
11:132437361:T:A	acceptor_loss	1.0000

AlphaMissense

2202 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:132436676:C:A	W256C	1.000
11:132436676:C:G	W256C	1.000
11:132436678:A:G	W256R	1.000
11:132436678:A:T	W256R	1.000
11:132529080:C:A	W169C	1.000
11:132529080:C:G	W169C	1.000
11:132436123:G:C	N300K	0.999
11:132436123:G:T	N300K	0.999
11:132436124:T:A	N300I	0.999
11:132436136:C:G	C296S	0.999
11:132436137:A:G	C296R	0.999
11:132436137:A:T	C296S	0.999
11:132436181:A:G	L281P	0.999
11:132436677:C:G	W256S	0.999
11:132436714:A:G	C244R	0.999
11:132437268:G:C	N206K	0.999
11:132437268:G:T	N206K	0.999
11:132437281:C:G	C202S	0.999
11:132437282:A:G	C202R	0.999
11:132437282:A:T	C202S	0.999
11:132437288:A:C	Y200D	0.999
11:132529081:C:G	W169S	0.999
11:132529082:A:G	W169R	0.999
11:132529082:A:T	W169R	0.999
11:132529116:A:C	C157W	0.999
11:132657098:A:G	L130P	0.999
11:132657142:G:C	C115W	0.999
11:132657143:C:G	C115S	0.999
11:132657144:A:G	C115R	0.999
11:132657144:A:T	C115S	0.999

dbSNP variants (sampled 300 via entrez): RS1000000250 (11:132836394 C>T), RS1000003867 (11:132739010 C>A,T), RS1000007331 (11:133208378 A>G), RS1000014239 (11:132919353 C>G), RS1000017875 (11:132837186 T>A,C), RS1000018767 (11:132599420 A>T), RS1000019039 (11:132497956 C>A,G,T), RS1000021855 (11:132996399 C>A,T), RS1000024347 (11:132580584 T>A), RS1000024594 (11:132647267 T>C), RS1000026444 (11:133231987 C>G,T), RS1000031823 (11:132895848 G>T), RS1000033479 (11:133208243 A>G), RS1000035993 (11:133483789 C>A,G,T), RS1000036379 (11:132739177 A>T)

Disease associations

OMIM: gene MIM:600632 | disease phenotypes: MIM:181500

GenCC curated gene-disease

Mondo (2): schizophrenia (MONDO:0005090), ovarian neoplasm (MONDO:0021068)

Orphanet (1): NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

5 total (6 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0003002	Breast carcinoma
HP:0006774	Ovarian papillary adenocarcinoma
HP:0100621	Dysgerminoma
HP:0100753	Schizophrenia

GWAS associations

33 associations (top):

Study	Trait	p-value
GCST000081_5	Sleep-related phenotypes	6.000000e-06
GCST001524_4	Visceral adipose tissue/subcutaneous adipose tissue ratio	1.000000e-06
GCST001737_20	Chronic obstructive pulmonary disease-related biomarkers	8.000000e-06
GCST002134_3	Alcohol dependence	7.000000e-06
GCST002138_3	Waist-hip ratio	4.000000e-07
GCST002337_58	Amyotrophic lateral sclerosis (sporadic)	8.000000e-09
GCST002587_17	Blood pressure (smoking interaction)	7.000000e-08
GCST002985_3	Middle childhood and early adolescence aggressive behavior	2.000000e-06
GCST003010_2	Gastric cancer	2.000000e-06
GCST003672_7	Docetaxel-induced peripheral neuropathy in metastatic castrate-resistant prostate cancer	4.000000e-06
GCST004068_21	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	9.000000e-06
GCST004714_3	Heart rate variability traits (SDNN)	8.000000e-07
GCST005830_66	Hand grip strength	3.000000e-09
GCST006479_68	Diverticular disease	7.000000e-07
GCST006575_20	Takayasu arteritis	9.000000e-06
GCST007327_12	Smoking status (ever vs never smokers)	2.000000e-08
GCST007327_135	Smoking status (ever vs never smokers)	4.000000e-09
GCST007327_177	Smoking status (ever vs never smokers)	2.000000e-12
GCST007327_40	Smoking status (ever vs never smokers)	9.000000e-09
GCST008507_1	Stress sensitivity (neuroticism score x major depressive disorder status interaction)	4.000000e-07
GCST008507_3	Stress sensitivity (neuroticism score x major depressive disorder status interaction)	3.000000e-06
GCST008508_7	Stress sensitivity (neuroticism score x major depressive disorder status interaction)	7.000000e-06
GCST008526_5	Coffee consumption	3.000000e-07
GCST009440_9	Age-related cognitive decline (attention/processing speed) (slope of z-scores)	7.000000e-06
GCST009849_10	Hallux valgus	2.000000e-06
GCST010002_203	Refractive error	7.000000e-29
GCST010396_104	Gut microbiota (bacterial taxa, hurdle binary method)	5.000000e-07
GCST010988_434	Adult body size	3.000000e-10
GCST012163_4	Adiponectin levels x Mediterranean diet adherence interaction	5.000000e-06
GCST012420_5	tricyclic pyrone compound response (IC50)	4.000000e-06

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0004343	waist-hip ratio
EFO:0006335	systolic blood pressure
EFO:0006526	pack-years measurement
EFO:0008003	heart rate variability measurement
EFO:0006941	grip strength measurement
EFO:0009959	diverticular disease
EFO:0004318	smoking behavior
EFO:0007660	neuroticism measurement
EFO:0006781	coffee consumption measurement
EFO:0007710	cognitive decline measurement
EFO:0007874	gut microbiome measurement
EFO:0004502	adiponectin measurement
EFO:0008111	diet measurement
EFO:0600033	response to mitochondrial complex I inhibitor
EFO:0600011	Parkinson’s disease symptom measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs751655	Efficacy	3	methylphenidate	Attention Deficit Disorder with Hyperactivity

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs751655	OPCML	3	0.00	1	methylphenidate

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, increases methylation	7
trichostatin A	affects cotreatment, increases expression	3
entinostat	increases expression, affects cotreatment, decreases expression	2
Vorinostat	affects cotreatment, increases expression, decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
bisphenol F	decreases methylation	1
bisphenol A	affects methylation, affects cotreatment, increases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
titanium dioxide	increases expression	1
arsenite	increases methylation	1
sodium arsenite	affects methylation	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects methylation, affects cotreatment, increases methylation	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Niclosamide	increases expression	1
Pesticides	increases methylation	1
Rotenone	decreases expression	1
Tobacco Smoke Pollution	increases methylation	1
Triclosan	decreases expression	1
Aflatoxin B1	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety