ITPR2

Summary

ITPR2 (inositol 1,4,5-trisphosphate receptor type 2, HGNC:6181) is a protein-coding gene on chromosome 12p11.23, encoding Inositol 1,4,5-trisphosphate-gated calcium channel ITPR2 (Q14571). Inositol 1,4,5-trisphosphate-gated calcium channel that upon inositol 1,4,5-trisphosphate binding transports calcium from the endoplasmic reticulum lumen to cytoplasm.

The protein encoded by this gene belongs to the inositol 1,4,5-triphosphate receptor family, whose members are second messenger intracellular calcium release channels. These proteins mediate a rise in cytoplasmic calcium in response to receptor activated production of inositol triphosphate. Inositol triphosphate receptor-mediated signaling is involved in many processes including cell migration, cell division, smooth muscle contraction, and neuronal signaling. This protein is a type 2 receptor that consists of a cytoplasmic amino-terminus that binds inositol triphosphate, six membrane-spanning helices that contribute to the ion pore, and a short cytoplasmic carboxy-terminus. A mutation in this gene has been associated with anhidrosis, suggesting that intracellular calcium release mediated by this protein is required for eccrine sweat production.

Source: NCBI Gene 3709 — RefSeq curated summary.

At a glance

• Gene–disease (curated): isolated anhidrosis with normal sweat glands (Supportive, GenCC)
• GWAS associations: 84
• Clinical variants (ClinVar): 371 total — 2 pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes
• MANE Select transcript: NM_002223

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6181
Approved symbol	ITPR2
Name	inositol 1,4,5-trisphosphate receptor type 2
Location	12p11.23
Locus type	gene with protein product
Status	Approved
Aliases	IP3R2, CFAP48
Ensembl gene	ENSG00000123104
Ensembl biotype	protein_coding
OMIM	600144
Entrez	3709

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 3 protein_coding_CDS_not_defined, 3 retained_intron, 2 protein_coding, 2 nonsense_mediated_decay

ENST00000242737, ENST00000381340, ENST00000451599, ENST00000536627, ENST00000538984, ENST00000540429, ENST00000540791, ENST00000543958, ENST00000545235, ENST00000545902

RefSeq mRNA: 3 — MANE Select: NM_002223 NM_001414174, NM_001414175, NM_002223

CCDS: CCDS41764

Canonical transcript exons

ENST00000381340 — 57 exons

Exon	Start	End
ENSE00001488260	26335352	26339483
ENSE00001488261	26340167	26340328
ENSE00001488263	26387434	26387594
ENSE00001488290	26487068	26487251
ENSE00001488291	26494153	26494340
ENSE00001488292	26495152	26495260
ENSE00001488294	26550247	26550355
ENSE00001488297	26556233	26556375
ENSE00001488298	26561762	26561952
ENSE00001488300	26578713	26578833
ENSE00001488302	26580027	26580155
ENSE00001488304	26595465	26595590
ENSE00001488306	26596883	26597134
ENSE00001488308	26599145	26599345
ENSE00001488309	26599987	26600109
ENSE00001488310	26602370	26602495
ENSE00001488312	26602617	26602706
ENSE00001488313	26621123	26621296
ENSE00001488319	26631866	26632059
ENSE00001488320	26653976	26654126
ENSE00001488321	26655708	26655852
ENSE00001488322	26656297	26656548
ENSE00001488324	26657707	26657892
ENSE00001488325	26658011	26658130
ENSE00001488326	26659113	26659285
ENSE00001488328	26663685	26663846
ENSE00001488329	26665910	26666051
ENSE00001488332	26681874	26682034
ENSE00001488333	26682574	26682673
ENSE00001488334	26686481	26686632
ENSE00001488335	26695606	26695650
ENSE00001488340	26715299	26715445
ENSE00001488341	26715752	26715835
ENSE00001488343	26716144	26716242
ENSE00001488348	26832690	26833194
ENSE00001602120	26790157	26790227
ENSE00003464550	26628033	26628162
ENSE00003467575	26427913	26428088
ENSE00003469369	26724656	26724742
ENSE00003479111	26486104	26486360
ENSE00003494789	26622240	26622405
ENSE00003496141	26443543	26443650
ENSE00003496421	26481131	26481241
ENSE00003515274	26400128	26400258
ENSE00003526274	26439127	26439319
ENSE00003540833	26483698	26483898
ENSE00003541635	26475296	26475418
ENSE00003562946	26624299	26624356
ENSE00003566948	26419049	26419213
ENSE00003572295	26722397	26722555
ENSE00003582056	26725650	26725765
ENSE00003582768	26415303	26415498
ENSE00003589588	26411320	26411412
ENSE00003621359	26476912	26477007
ENSE00003626369	26398876	26399041
ENSE00003652573	26711173	26711268
ENSE00003680829	26436221	26436346

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 94.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.5613 / max 343.7639, expressed in 1677 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130236	13.6125	1647
130238	0.3943	199
206653	0.3535	204
130235	0.2756	111
130239	0.2254	106
130237	0.2064	82
130234	0.1993	92
130229	0.0846	36
130228	0.0822	38
130231	0.0754	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	94.09	gold quality
adrenal tissue	UBERON:0018303	93.47	gold quality
germinal epithelium of ovary	UBERON:0001304	92.78	gold quality
upper leg skin	UBERON:0004262	90.58	gold quality
colonic epithelium	UBERON:0000397	90.46	gold quality
skin of hip	UBERON:0001554	90.41	gold quality
sural nerve	UBERON:0015488	90.36	gold quality
liver	UBERON:0002107	90.01	gold quality
oral cavity	UBERON:0000167	90.00	gold quality
tendon	UBERON:0000043	89.41	gold quality
bone marrow cell	CL:0002092	89.18	gold quality
mammary duct	UBERON:0001765	88.85	gold quality
epithelium of mammary gland	UBERON:0003244	88.58	gold quality
jejunal mucosa	UBERON:0000399	88.48	gold quality
tonsil	UBERON:0002372	87.10	gold quality
upper arm skin	UBERON:0004263	86.68	gold quality
caput epididymis	UBERON:0004358	86.61	gold quality
corpus epididymis	UBERON:0004359	86.58	gold quality
pigmented layer of retina	UBERON:0001782	86.24	gold quality
right lobe of liver	UBERON:0001114	85.78	gold quality
parotid gland	UBERON:0001831	85.71	gold quality
adrenal gland	UBERON:0002369	85.28	gold quality
corpus callosum	UBERON:0002336	85.25	gold quality
right adrenal gland	UBERON:0001233	84.88	gold quality
lower lobe of lung	UBERON:0008949	84.88	gold quality
left adrenal gland	UBERON:0001234	84.75	gold quality
right adrenal gland cortex	UBERON:0035827	84.64	gold quality
gingiva	UBERON:0001828	84.58	gold quality
mammary gland	UBERON:0001911	84.58	gold quality
left adrenal gland cortex	UBERON:0035825	84.53	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	70.83
E-CURD-119	yes	38.79
E-HCAD-25	yes	23.93
E-CURD-114	yes	11.58
E-ANND-3	yes	9.09
E-CURD-53	no	133.31
E-MTAB-8410	no	3.24

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYCN, NFATC1

miRNA regulators (miRDB)

194 targeting ITPR2, 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-340-5P	100.00	72.50	4437
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-3119	99.92	71.34	2390

Literature-anchored findings (GeneRIF, showing 31)

• Antibodies are detected most frequently in rheumatoid arthritis. (PMID:17437169)
• Genetic variation is susceptibility factor for amyotrophic lateral sclerosis(ALS). Involved in glutamate-mediated neurotransmission, is one of main regulators of intracellular calcium concentrations, and has important role in apoptosis. (PMID:17827064)
• Provide evidence for a functional role of the de novo coupling between hTRPC1 and IP3RII in the activation of store operated calcium entry in platelets. (PMID:18249094)
• Parathyroid hormone communicates with IP(3)R via “cAMP junctions” that allow local delivery of a supramaximal concentration of cAMP to IP(3)R, directly increasing their sensitivity to IP(3). (PMID:18936250)
• The result of this study suggested that ITPR2 that do not modulate the risk for SALS in the German population. (PMID:19464757)
• Elevated InsP(3)R2 expression was also detected in hearts from human patients with heart failure after ischemic dilated cardiomyopathy, as well as in aortic-banded hypertrophic mouse hearts. (PMID:19549843)
• Dystrophic (RCDMD) human muscle cells show 5-fold overexpression of IP(3)R2 and down-regulation of IP(3)R3 compared with normal human muscle cells. (PMID:20395455)
• The knock down of IP3R-2 significantly reduced the intracellular Ca2+ response and this reduced Ca2+ response did not affect the activation of CREB but significantly decreased the activation of NFAT. (PMID:21063100)
• ITPR2 is a functional target gene of the BACH1 transcription factor according to ChIP-seq and knockdown analysis in HEK 293 cells. (PMID:21555518)
• Functional IP3R2s are expressed in the mouse sinoatrial node and could serve as an additional divalent calcium ion-dependent mechanism in modulating cardiac pacemaker. (PMID:21852551)
• These data suggest that ER Ca(2+) released by IP(3) receptors may be detrimental in amyotrophic lateral sclerosis and that motor neurons are vulnerable to impaired Ca(2+) metabolism. (PMID:23131553)
• These results suggest an involvement of hydrogen sulfide in both IP3-induced calcium signalling and induction of apoptosis, possibly through the activation of endoplasmic reticulum stress. (PMID:23582047)
• Studies indicate that three subtypes of inositol 1,4,5-trisphosphate (IP3) receptors (IP3R1, -2, and -3) are assembled to form homo- and heterotetrameric channels that mediate Ca(2+) release from intracellular stores. (PMID:23955339)
• The Galphaq-protein/coupled receptor/IP3R axis modulates the electromechanical properties of the human myocardium and its propensity to develop arrhythmias. (PMID:23983250)
• ITPR2 and hypertrophy specific gene expression is regulated, in part, by a positive feedback regulation between InsP3R2 and calcineurin-NFATc signaling pathways. (PMID:24415751)
• results show a functional role of calcium release by the ITPR2 channel and its subsequent accumulation in the mitochondria (PMID:24797322)
• A genome-wide association study identifies ITPR2 as a susceptibility gene for Kashin-Beck disease in Han Chinese. (PMID:25303641)
• Loss of InsP3R2-mediated calcium release causes isolated anhidrosis in humans. (PMID:25329695)
• Disrupting IP3R/Bcl-2 interaction therefore leads in those cells to increased Ca(2) release and apoptosis. Intriguingly, IP3R2 is not only implicated in apoptosis but also in the induction of senescence, another tumour-suppressive mechanism. (PMID:25499268)
• High expression of inositol 1,4,5-trisphosphate receptor, type 2 is associated with acute myeloid leukemia. (PMID:25779662)
• Studies indicate that the ryanodine receptors (RyRs: RyR1, RyR2, RyR3) and inositol 1,4,5-trisphosphate receptors (IP3Rs: IP3R1, IP3R2, IP3R3) are the major Ca(2+) release channels (CRCs) on the endo/sarcoplasmic reticulum (ER/SR). (PMID:25966694)
• the ability to generate tetramers with defined wild type and mutant subunits will be useful in probing fundamental questions relating to IP3Rs (R1, R2, R3) structure and function. (PMID:26009177)
• Data suggest miR-1290 as the new oncomiR involved in laryngeal squamous cell carcinoma pathogenesis probably through downregulation of its target genes MAF and ITPR2. (PMID:26694163)
• we systematically evaluating RCC risk-associated SNPs indentified from previous GWAS in a Chinese population, finding that one SNP located in PDZD2 and two SNPs located in ITPR2 were ccRCC-risk associated in Chinese population. (PMID:26918600)
• Fatty liver induces a c-Jun-mediated decrease in ITPR2 in hepatocytes. (PMID:29023819)
• Molecular cloning, bacterial expression and protein purification of the IBC domain from human IP3R2 have been described. (PMID:30244130)
• The SNP rs11048526 were significantly association with Kashin-Beck Disease which increased the Kashin-Beck Disease risk. (PMID:31066235)
• Type 3 Inositol 1,4,5-Trisphosphate Receptor is a Crucial Regulator of Calcium Dynamics Mediated by Endoplasmic Reticulum in HEK Cells. (PMID:31979185)
• Calcium channel ITPR2 and mitochondria-ER contacts promote cellular senescence and aging. (PMID:33526781)
• Candidate Gene of NOS3, MMP3, AGT, and AGT1R and Pathway Analyses for Platelet Reactivity and Clinical Outcomes of Repeat Revascularization After First PCI in Chinese Patients. (PMID:34860335)
• Inositol 1,4,5-trisphosphate receptor gene variants are related to the risk of breast cancer in a Chinese population. (PMID:36350267)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	itpr2	ENSDARG00000011909
mus_musculus	Itpr2	ENSMUSG00000030287
rattus_norvegicus	Itpr2	ENSRNOG00000001804
drosophila_melanogaster	RyR	FBGN0011286
caenorhabditis_elegans		WBGENE00006801

Paralogs (5): ITPR3 (ENSG00000096433), ITPR1 (ENSG00000150995), RYR1 (ENSG00000196218), RYR2 (ENSG00000198626), RYR3 (ENSG00000198838)

Protein

Protein identifiers

Inositol 1,4,5-trisphosphate-gated calcium channel ITPR2 — Q14571 (reviewed: Q14571)

Alternative names: IP3 receptor isoform 2, Inositol 1,4,5-trisphosphate receptor type 2, Type 2 inositol 1,4,5-trisphosphate receptor

All UniProt accessions (3): Q14571, F5GYT5, H7C2X9

UniProt curated annotations — full annotation on UniProt →

Function. Inositol 1,4,5-trisphosphate-gated calcium channel that upon inositol 1,4,5-trisphosphate binding transports calcium from the endoplasmic reticulum lumen to cytoplasm. Exists in two states; a long-lived closed state where the channel is essentially ‘parked’ with only very rare visits to an open state and that ligands facilitate the transition from the ‘parked’ state into a ‘drive’ mode represented by periods of bursting activity.

Subunit / interactions. Homotetramer. Interacts with CABP1. Interacts with BOK; regulates ITPR2 expression. Interacts with BCL2L10. Interacts with TRPC4. Interacts with CHGA and CHGB.

Subcellular location. Endoplasmic reticulum membrane. Cytoplasmic vesicle. Secretory vesicle membrane.

Tissue specificity. Found in skeletal muscle and heart.

Post-translational modifications. Phosphorylation by cAMP-dependent PKA on Ser-937 increases calcium release. Phosphorylation by CaMK2 on Ser-150 significantly decreases the channel open probability.

Disease relevance. Anhidrosis, isolated, with normal sweat glands (ANHD) [MIM:106190] An autosomal recessive disorder characterized by generalized, isolated anhidrosis, severe heat intolerance, and morphologically normal eccrine sweat glands. Body growth, teeth, hair, nails, and skin are normal. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inositol 1,4,5-trisphosphate-gated calcium channel activity is increased by cAMP that occurs independently of PKA activation. ATP and cytosolic calcium modulate the open probability (Po) predominantly by facilitating extended ‘bursting’ activity of the channel. Inositol 1,4,5-trisphosphate-gated calcium channel activity is inhibited by CALM1 in a calcium-dependent manner.

Similarity. Belongs to the InsP3 receptor family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14571-1	Long	yes
Q14571-2	Short, TIPR

RefSeq proteins (3): NP_001401103, NP_001401104, NP_002214* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000493	InsP3_rcpt	Family
IPR000699	RIH_dom	Domain
IPR005821	Ion_trans_dom	Domain
IPR013662	RIH_assoc-dom	Domain
IPR014821	Ins145_P3_rcpt	Domain
IPR015925	Ryanodine_IP3_receptor	Family
IPR016024	ARM-type_fold	Homologous_superfamily
IPR016093	MIR_motif	Domain
IPR035910	RyR/IP3R_RIH_dom_sf	Homologous_superfamily
IPR036300	MIR_dom_sf	Homologous_superfamily

Pfam: PF00520, PF01365, PF02815, PF08454, PF08709

Catalyzed reactions (Rhea), 1 shown:

• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)

UniProt features (63 total): binding site 28, topological domain 7, transmembrane region 6, modified residue 6, domain 5, sequence variant 4, sequence conflict 3, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q14571 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (28): 265; 267; 268; 269; 503; 507; 510; 567; 568; 569; 744; 1124 …

Post-translational modifications (6): 937, 1160, 1709, 2607, 2633, 2636

Function

Pathways and Gene Ontology

Reactome pathways

49 pathways

ID	Pathway
R-HSA-112043	PLC beta mediated events
R-HSA-114508	Effects of PIP2 hydrolysis
R-HSA-139853	Elevation of cytosolic Ca2+ levels
R-HSA-1489509	DAG and IP3 signaling
R-HSA-2029485	Role of phospholipids in phagocytosis
R-HSA-2871809	FCERI mediated Ca+2 mobilization
R-HSA-381676	Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-4086398	Ca2+ pathway
R-HSA-422356	Regulation of insulin secretion
R-HSA-5218921	VEGFR2 mediated cell proliferation
R-HSA-5578775	Ion homeostasis
R-HSA-5607763	CLEC7A (Dectin-1) induces NFAT activation
R-HSA-9664323	FCGR3A-mediated IL10 synthesis
R-HSA-983695	Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
R-HSA-109582	Hemostasis
R-HSA-111885	Opioid Signalling
R-HSA-112040	G-protein mediated events
R-HSA-1280218	Adaptive Immune System
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-163685	Integration of energy metabolism
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-194138	Signaling by VEGF
R-HSA-195721	Signaling by WNT
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-2454202	Fc epsilon receptor (FCERI) signaling
R-HSA-372790	Signaling by GPCR
R-HSA-3858494	Beta-catenin independent WNT signaling

MSigDB gene sets: 416 (showing top): MORF_RAGE, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, MORF_FLT1, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, BASSO_B_LYMPHOCYTE_NETWORK, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, CERVERA_SDHB_TARGETS_1_DN, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_1, RIZKI_TUMOR_INVASIVENESS_3D_DN, MORF_ESR1, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_MONOATOMIC_CATION_TRANSPORT

GO Biological Process (11): response to hypoxia (GO:0001666), signal transduction (GO:0007165), release of sequestered calcium ion into cytosol (GO:0051209), cellular response to cAMP (GO:0071320), cellular response to ethanol (GO:0071361), monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816), calcium-mediated signaling (GO:0019722), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085), calcium ion transmembrane transport (GO:0070588)

GO Molecular Function (13): inositol 1,4,5-trisphosphate-gated calcium channel activity (GO:0005220), calcium ion binding (GO:0005509), ATP binding (GO:0005524), calcium ion transmembrane transporter activity (GO:0015085), phosphatidylinositol binding (GO:0035091), transmembrane transporter binding (GO:0044325), inositol 1,4,5 trisphosphate binding (GO:0070679), scaffold protein binding (GO:0097110), nucleotide binding (GO:0000166), monoatomic ion channel activity (GO:0005216), calcium channel activity (GO:0005262), intracellularly gated calcium channel activity (GO:0015278), metal ion binding (GO:0046872)

GO Cellular Component (13): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), cell cortex (GO:0005938), membrane (GO:0016020), sarcoplasmic reticulum (GO:0016529), transport vesicle membrane (GO:0030658), secretory granule membrane (GO:0030667), platelet dense tubular network membrane (GO:0031095), sarcoplasmic reticulum membrane (GO:0033017), signaling receptor complex (GO:0043235), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
G-protein mediated events	1
G alpha (q) signalling events	1
Platelet activation, signaling and aggregation	1
Platelet calcium homeostasis	1
Intracellular signaling by second messengers	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
Fc epsilon receptor (FCERI) signaling	1
Regulation of insulin secretion	1
Beta-catenin independent WNT signaling	1
Integration of energy metabolism	1
VEGFA-VEGFR2 Pathway	1
Cardiac conduction	1
CLEC7A (Dectin-1) signaling	1
Anti-inflammatory response favouring Leishmania parasite infection	1
Signaling by the B Cell Receptor (BCR)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
bounding membrane of organelle	4
cytoplasm	3
cellular process	2
transport	2
anion binding	2
protein binding	2
cell periphery	2
cellular anatomical structure	2
cytoplasmic vesicle membrane	2
response to stress	1
response to decreased oxygen levels	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intercellular transport	1
calcium ion transmembrane import into cytosol	1
response to cAMP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
response to ethanol	1
cellular response to alcohol	1
metal ion transport	1
intracellular signaling cassette	1
monoatomic ion transport	1
transmembrane transport	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
intracellularly gated calcium channel activity	1
inositol 1,4,5 trisphosphate binding	1
metal ion binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
metal ion transmembrane transporter activity	1
calcium ion transmembrane transport	1
alcohol binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
monoatomic ion transmembrane transporter activity	1
channel activity	1

Protein interactions and networks

STRING

1537 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITPR2	FUNDC1	Q8IVP5	978
ITPR2	TRPC3	Q13507	907
ITPR2	SSPN	Q14714	781
ITPR2	VDAC1	P21796	776
ITPR2	MPP4	Q96JB8	750
ITPR2	ADCY6	O43306	730
ITPR2	ATP2A2	P16614	705
ITPR2	TRPC1	P48995	700
ITPR2	LYN	P07948	683
ITPR2	GRK7	Q8WTQ7	669
ITPR2	STIM1	Q13586	659
ITPR2	GRK1	Q15835	649
ITPR2	DPP6	P42658	617
ITPR2	BANK1	Q8NDB2	599
ITPR2	ATP2A1	O14983	592

IntAct

86 interactions, top by confidence:

A	B	Type	Score
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
SLC16A3	CASK	psi-mi:“MI:0914”(association)	0.590
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
CACNG2	CCNT1	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
CA8	IGLL5	psi-mi:“MI:0914”(association)	0.530
TAFA4	NRP1	psi-mi:“MI:0914”(association)	0.530
RAB29	CHM	psi-mi:“MI:0914”(association)	0.530
BBOX1	ITPRID2	psi-mi:“MI:0914”(association)	0.530
TRPC4	ITPR2	psi-mi:“MI:0915”(physical association)	0.530
TRPC4	ITPR2	psi-mi:“MI:0407”(direct interaction)	0.530
ITPR2	EIF4G1	psi-mi:“MI:0915”(physical association)	0.400
ITPR2	BCL2L10	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
Lima1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Myo1c	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CAPZA2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MYH9	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Sumo3	GABPB1	psi-mi:“MI:0914”(association)	0.350
NUP107	POM121C	psi-mi:“MI:0914”(association)	0.350
CAMK2D	DVL2	psi-mi:“MI:0914”(association)	0.350
SLC15A3		psi-mi:“MI:0914”(association)	0.350

BioGRID (192): ITPR2 (Affinity Capture-RNA), ITPR2 (Affinity Capture-MS), ITPR2 (Affinity Capture-MS), ITPR2 (Affinity Capture-MS), ITPR2 (Affinity Capture-MS), ITPR2 (Affinity Capture-MS), ITPR2 (Affinity Capture-MS), ITPR2 (Affinity Capture-MS), ITPR2 (Affinity Capture-MS), ITPR2 (Affinity Capture-MS), ITPR2 (Affinity Capture-MS), ITPR2 (Affinity Capture-MS), ITPR2 (Affinity Capture-MS), ITPR2 (Affinity Capture-MS), ITPR2 (Affinity Capture-MS)

ESM2 similar proteins: A2AGL3, B0LPN4, E9PZQ0, E9Q401, F1LMY4, F1Q8X5, P0C7A6, P11716, P11881, P16960, P21817, P29994, P29995, P30957, P42694, P48553, Q0VEJ0, Q14571, Q14643, Q15413, Q1LVW0, Q24498, Q28C34, Q3TLI0, Q5F361, Q5RCP7, Q6NRC7, Q6NRD0, Q6NYU2, Q6QI06, Q6R327, Q7SXV1, Q7Z3V4, Q7ZUV0, Q7ZYD9, Q80UK0, Q86VW0, Q8BHL5, Q8BIK4, Q8BWW9

Diamond homologs: A2AGL3, B0LPN4, E9PZQ0, E9Q401, F1LMY4, P11716, P11881, P16960, P21817, P29993, P29994, P29995, P30957, P70227, Q14571, Q14573, Q14643, Q15413, Q24498, Q5R881, Q63269, Q8BVR6, Q8WN95, Q8WN96, Q8WSR4, Q92736, Q95LP3, Q96DX4, Q9TS33, Q9TU34, Q9Y0A1, Q9Z329, A0A5F9C6I2, D3ZXK7, Q5XPI3, Q5XPI4, Q9SIZ8, Q9VNV3, Q19614, Q91X20

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
RNF170	“down-regulates activity”	ITPR2	polyubiquitination
CAMK2D	“down-regulates activity”	ITPR2	phosphorylation
Erlin	“down-regulates quantity by destabilization”	ITPR2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 108 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
Glutamate binding, activation of AMPA receptors and synaptic plasticity	5	52.1×	1e-05
Trafficking of AMPA receptors	5	37.2×	4e-05
G-protein mediated events	5	22.4×	2e-04
DAG and IP3 signaling	5	21.7×	2e-04
Opioid Signalling	5	18.2×	4e-04
PLC beta mediated events	5	18.2×	4e-04
Assembly and cell surface presentation of NMDA receptors	5	17.4×	4e-04
Ion homeostasis	5	14.0×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
long-term synaptic potentiation	6	18.1×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	264
Likely benign	30
Benign	20

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
189316	NM_002223.4(ITPR2):c.7492G>A (p.Gly2498Ser)	Pathogenic
4082119	NM_002223.4(ITPR2):c.7391del (p.Ala2463_Ser2464insTer)	Pathogenic

SpliceAI

12019 predictions. Top by Δscore:

Variant	Effect	Δscore
12:26340164:CACCT:C	donor_loss	1.0000
12:26340165:A:AC	donor_gain	1.0000
12:26340166:C:CC	donor_gain	1.0000
12:26340166:C:CG	donor_loss	1.0000
12:26340166:CCTG:C	donor_gain	1.0000
12:26340329:C:CC	acceptor_gain	1.0000
12:26387592:GTCC:G	acceptor_loss	1.0000
12:26387593:TCCTG:T	acceptor_loss	1.0000
12:26387594:CCTG:C	acceptor_loss	1.0000
12:26387595:CTG:C	acceptor_loss	1.0000
12:26387596:T:C	acceptor_loss	1.0000
12:26398875:CCA:C	donor_gain	1.0000
12:26398960:C:CT	acceptor_gain	1.0000
12:26400116:A:AC	donor_gain	1.0000
12:26400117:C:CC	donor_gain	1.0000
12:26400117:CT:C	donor_gain	1.0000
12:26400123:CTTA:C	donor_loss	1.0000
12:26400124:TTA:T	donor_loss	1.0000
12:26400125:TA:T	donor_loss	1.0000
12:26400126:A:AC	donor_gain	1.0000
12:26400126:ACAT:A	donor_gain	1.0000
12:26400127:C:CC	donor_gain	1.0000
12:26400127:CA:C	donor_gain	1.0000
12:26400127:CAT:C	donor_gain	1.0000
12:26400127:CATC:C	donor_gain	1.0000
12:26400172:T:TA	donor_gain	1.0000
12:26400255:TCAG:T	acceptor_gain	1.0000
12:26400256:CAG:C	acceptor_gain	1.0000
12:26400256:CAGC:C	acceptor_gain	1.0000
12:26400257:AG:A	acceptor_gain	1.0000

AlphaMissense

17997 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:26340313:A:G	W2625R	1.000
12:26340313:A:T	W2625R	1.000
12:26398888:A:G	C2562R	1.000
12:26398932:A:G	L2547P	1.000
12:26398940:A:C	F2544L	1.000
12:26398940:A:T	F2544L	1.000
12:26398942:A:G	F2544L	1.000
12:26398961:A:C	F2537L	1.000
12:26398961:A:T	F2537L	1.000
12:26398963:A:G	F2537L	1.000
12:26398970:G:C	N2534K	1.000
12:26398970:G:T	N2534K	1.000
12:26398974:A:G	L2533P	1.000
12:26399007:A:G	L2522P	1.000
12:26400177:A:T	L2494H	1.000
12:26400181:C:G	G2493R	1.000
12:26400203:G:C	C2485W	1.000
12:26400205:A:G	C2485R	1.000
12:26400222:C:T	C2479Y	1.000
12:26419184:A:C	S2325R	1.000
12:26419184:A:T	S2325R	1.000
12:26419186:T:G	S2325R	1.000
12:26436305:A:G	W2229R	1.000
12:26436305:A:T	W2229R	1.000
12:26595529:T:A	K1439I	1.000
12:26602428:A:G	L1207P	1.000
12:26621200:A:G	W1129R	1.000
12:26621200:A:T	W1129R	1.000
12:26621229:A:G	L1119P	1.000
12:26621238:A:G	L1116P	1.000

dbSNP variants (sampled 300 via entrez): RS1000002964 (12:26513384 T>C), RS1000005391 (12:26508856 G>A), RS1000014796 (12:26711503 C>A), RS1000016461 (12:26835011 A>C,G), RS1000017411 (12:26568834 C>A,T), RS1000018241 (12:26524833 T>C), RS1000022818 (12:26564979 G>A,T), RS1000025588 (12:26397058 G>A), RS1000031533 (12:26759109 T>C), RS1000047842 (12:26434629 T>A), RS1000051688 (12:26346867 G>A), RS1000058526 (12:26429529 C>T), RS1000059345 (12:26386927 C>A), RS1000061103 (12:26558377 A>C), RS1000062199 (12:26440521 T>C)

Disease associations

OMIM: gene MIM:600144 | disease phenotypes: MIM:106190, MIM:143890

GenCC curated gene-disease

Disease	Classification	Inheritance
isolated anhidrosis with normal sweat glands	Supportive	Autosomal recessive

Mondo (3): isolated anhidrosis with normal sweat glands (MONDO:0007118), familial hypercholesterolemia (MONDO:0005439), intellectual disability (MONDO:0001071)

Orphanet (2): Isolated generalized anhidrosis with normal sweat glands (Orphanet:468666), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001507	Growth abnormality
HP:0001595	Abnormal hair morphology
HP:0002046	Heat intolerance
HP:0007459	Generalized anhidrosis

GWAS associations

84 associations (top):

Study	Trait	p-value
GCST000072_1	Amyotrophic lateral sclerosis	3.000000e-06
GCST000829_5	Waist-hip ratio	1.000000e-17
GCST001283_1	Renal cell carcinoma	9.000000e-10
GCST002361_5	Smooth-surface caries	3.000000e-06
GCST002634_1	Kashin-Beck disease	1.000000e-11
GCST002782_53	Waist-to-hip ratio adjusted for body mass index	6.000000e-15
GCST002782_54	Waist-to-hip ratio adjusted for body mass index	4.000000e-16
GCST002782_55	Waist-to-hip ratio adjusted for body mass index	5.000000e-15
GCST002782_56	Waist-to-hip ratio adjusted for body mass index	2.000000e-15
GCST003983_22	Male-pattern baldness	4.000000e-12
GCST004064_4	Waist-hip ratio	2.000000e-11
GCST004064_40	Waist-hip ratio	6.000000e-12
GCST004505_62	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	1.000000e-13
GCST004505_63	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	9.000000e-16
GCST004507_15	Waist-to-hip ratio adjusted for BMI (joint analysis main effects and smoking interaction)	5.000000e-06
GCST004508_10	Waist-to-hip ratio adjusted for BMI in non-smokers	2.000000e-06
GCST004562_144	Waist circumference adjusted for body mass index	4.000000e-09
GCST004562_243	Waist circumference adjusted for body mass index	1.000000e-09
GCST004563_126	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	8.000000e-09
GCST004563_205	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	7.000000e-09
GCST004563_21	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-08
GCST004564_217	Waist circumference adjusted for BMI in active individuals	3.000000e-06
GCST004564_218	Waist circumference adjusted for BMI in active individuals	1.000000e-07
GCST004564_219	Waist circumference adjusted for BMI in active individuals	2.000000e-06
GCST004567_10	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	4.000000e-16
GCST004567_102	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	2.000000e-16
GCST004567_29	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	6.000000e-17
GCST004567_91	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	4.000000e-18
GCST004576_101	Waist-to-hip ratio adjusted for body mass index	6.000000e-18
GCST004576_138	Waist-to-hip ratio adjusted for body mass index	4.000000e-19

EFO canonical traits (21, from GWAS)

EFO ID	Trait name
EFO:0004343	waist-hip ratio
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004318	smoking behavior
EFO:0007789	BMI-adjusted waist circumference
EFO:0008002	physical activity measurement
EFO:0004344	birth weight
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009443	BRCAX breast cancer
EFO:0009270	heel bone mineral density
EFO:0005939	parental genotype effect measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0004531	urate measurement
EFO:0004587	lymphocyte count
EFO:0007985	platelet crit
EFO:0004533	alkaline phosphatase measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2111451 (PROTEIN FAMILY)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: lgic — IP₃ receptors

ChEMBL bioactivities

9 potent at pChembl≥5 of 12 total, top 9 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.35	IC50	4.43	nM	INS(1,4,5)P3
7.85	IC50	14	nM	CHEMBL3349691
7.58	IC50	26.5	nM	CHEMBL3349691
7.47	IC50	33.5	nM	INS(1,4,5)P3
7.28	IC50	52	nM	INS(1,4,5)P3
6.89	EC50	130	nM	CHEMBL1161456
6.76	IC50	172	nM	CHEMBL1160286
6.70	IC50	200	nM	INS(1,4,5)P3
6.39	EC50	410	nM	CHEMBL1161466

PubChem BioAssay actives

6 with measured affinity, of 6 total; 3 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
[(1R,2S,3R,4R,5S,6R)-2,3,5-trihydroxy-4,6-diphosphonooxycyclohexyl] dihydrogen phosphate	92895: The compound was tested for inhibitory activity against IInositol 1,4,5-trisphosphate receptor in SH-SY5Y cell line	ic50	0.0044	uM
[(1S,2R,4R,5R)-2,4-dihydroxy-3,5,6-triphosphonooxycyclohexyl] dihydrogen phosphate	92896: The compound was tested for inhibitory activity against Inositol 1,4,5-trisphosphate receptor in SH-SY5Y cell line	ic50	0.0140	uM
(2,5-dihydroxy-3,4,6-triphosphonooxycyclohexyl)oxy-trihydroxyphosphanium	92898: The compound was tested for inhibitory activity against Inositol 1,4,5-trisphosphate receptor in L15 cell line	ic50	0.1720	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, affects methylation, decreases expression	8
Valproic Acid	affects cotreatment, increases expression, decreases expression, decreases methylation	7
Tretinoin	affects expression, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
potassium chromate(VI)	decreases expression, affects cotreatment	2
mercuric bromide	increases expression, affects cotreatment	2
perfluorooctane sulfonic acid	affects expression, affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Cisplatin	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
Particulate Matter	affects response to substance, decreases expression	2
aristolochic acid I	decreases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
beta-lapachone	decreases expression	1
sodium bichromate	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
benzo(e)pyrene	decreases methylation	1
periodate-oxidized adenosine	affects expression	1

ChEMBL screening assays

8 unique, capped per target: 7 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL697190	Binding	Compound was evaluated for its ability to inhibit Inositol phosphorylation	Total synthesis of L-2,2-difluoro-2-deoxy-MYO-inositol 1,4,5-trisphosphate, a potent inhibitor of the enzymes of d-MYO-inositol 1,4,5-trisphosphate metabolism — Bioorg Med Chem Lett
CHEMBL699700	Functional	Compound was evaluated for its effective dose to inhibit the calcium release as a measure of affinity for Inositol 1,4,5-trisphosphate receptor	Total synthesis of L-2,2-difluoro-2-deoxy-MYO-inositol 1,4,5-trisphosphate, a potent inhibitor of the enzymes of d-MYO-inositol 1,4,5-trisphosphate metabolism — Bioorg Med Chem Lett

Cellosaurus cell lines

12 cell lines: 7 cancer cell line, 5 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7SV	Ubigene A-549 ITPR2 KO	Cancer cell line	Male
CVCL_D8NM	Ubigene HCT 116 ITPR2 KO	Cancer cell line	Male
CVCL_D9HM	Ubigene HEK293 ITPR2 KO	Transformed cell line	Female
CVCL_E0FR	Ubigene HeLa ITPR2 KO	Cancer cell line	Female
CVCL_HB82	HEK-3KO	Transformed cell line	Female
CVCL_HB83	HEKR1	Transformed cell line	Female
CVCL_HB85	HEKR2R1	Transformed cell line	Female
CVCL_HB86	HEKR2R3	Transformed cell line	Female
CVCL_ST60	HAP1 ITPR2 (-) 1	Cancer cell line	Male
CVCL_ST61	HAP1 ITPR2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00655265	PHASE4	COMPLETED	A Study of the Safety and Efficacy of Patients With Familial Hypercholesterolaemia Taking Colesevelam as add-on Therapy to Their Existing Medication
NCT00916643	PHASE4	COMPLETED	Low-Density Lipoprotein (LDL) Apheresis Using H.E.L.P. Therapy
NCT03331666	PHASE4	TERMINATED	Impact of LDL-cholesterol Lowering on Platelet Activation
NCT05465278	PHASE4	COMPLETED	Alirocumab and Plaque Burden In Familial Hypercholesterolaemia
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00355615	PHASE3	COMPLETED	PLUTO: Pediatric Lipid-redUction Trial of rOsuvastatin
NCT00552097	PHASE3	COMPLETED	Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE)(P02578)
NCT00607373	PHASE3	COMPLETED	Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia
NCT00694109	PHASE3	COMPLETED	An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia
NCT00827606	PHASE3	COMPLETED	Atorvastatin Three Year Pediatric Study
NCT00943306	PHASE3	COMPLETED	Long Term, Follow-on Study of Lomitapide in Patients With Homozygous Familial Hypercholesterolemia
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT01813006	PHASE3	COMPLETED	Effect of Omega-3 Fatty Acid on Endothelial Function
NCT01841684	PHASE3	TERMINATED	Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042)
NCT02624869	PHASE3	COMPLETED	Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia)
NCT02748057	PHASE3	COMPLETED	A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653H in Japanese Participants With Hypercholesterolemia (MK-0653H-833)
NCT03884452	PHASE3	COMPLETED	Ezetimibe (SCH 58235) Taken With Either Atorvastatin or Simvastatin in Participants With Familial Hypercholesterolemia (MK-0653-018)
NCT04798430	PHASE3	ENROLLING_BY_INVITATION	Long-term Efficacy and Safety of OLE LIB003 in HoFH, HeFH, and High-risk CVD Patients Requiring Further LDL-C Reduction
NCT05142722	PHASE3	COMPLETED	Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT05238519	PHASE3	ACTIVE_NOT_RECRUITING	Improved Diagnosis of Familial Hypercholesterolemia Across the Northland (ID-FH)
NCT05425745	PHASE3	COMPLETED	Evaluate the Effect of Obicetrapib in Patients With HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies.
NCT05952856	PHASE3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-013) CORALreef Lipids
NCT05952869	PHASE3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017/CORALreef HeFH)
NCT06005597	PHASE3	COMPLETED	Study of Obicetrapib & Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00079846	PHASE2	TERMINATED	Implitapide in Patients With Homozygous Familial Hypercholesterolemia (HoFH) on Maximal Concurrent Lipid-Lowering Therapy
NCT00079859	PHASE2	TERMINATED	Implitapide in Patients With Heterozygous Familial Hypercholesterolemia (HeFH) on Maximal Concurrent Lipid-Lowering Therapy
NCT00477594	PHASE2	COMPLETED	Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia
NCT00751608	PHASE2	WITHDRAWN	Effect of APL180 on Endothelial Function in Familial Hypercholesterolemia Patients
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