ITPR3

Summary

ITPR3 (inositol 1,4,5-trisphosphate receptor type 3, HGNC:6182) is a protein-coding gene on chromosome 6p21.31, encoding Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 (Q14573). Inositol 1,4,5-trisphosphate-gated calcium channel that, upon 1D-myo-inositol 1,4,5-trisphosphate binding, transports calcium from the endoplasmic reticulum lumen to cytoplasm, thus releasing the intracellular calcium and therefore participates in cellular calcium ion homeostasi….

This gene encodes a receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. The receptor contains a calcium channel at the C-terminus and the ligand-binding site at the N-terminus. Knockout studies in mice suggest that type 2 and type 3 inositol 1,4,5-trisphosphate receptors play a key role in exocrine secretion underlying energy metabolism and growth.

Source: NCBI Gene 3710 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Charcot-Marie-Tooth disease, demyelinating, type 1J (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 13
• Clinical variants (ClinVar): 700 total — 3 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 158
• Druggable target: yes
• MANE Select transcript: NM_002224

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6182
Approved symbol	ITPR3
Name	inositol 1,4,5-trisphosphate receptor type 3
Location	6p21.31
Locus type	gene with protein product
Status	Approved
Aliases	IP3R3
Ensembl gene	ENSG00000096433
Ensembl biotype	protein_coding
OMIM	147267
Entrez	3710

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000374316, ENST00000605930, ENST00000931640

RefSeq mRNA: 1 — MANE Select: NM_002224 NM_002224

CCDS: CCDS4783

Canonical transcript exons

ENST00000605930 — 58 exons

Exon	Start	End
ENSE00003697166	33621322	33621691
ENSE00003699873	33695712	33696562
ENSE00003888683	33663500	33663550
ENSE00003888705	33688239	33688431
ENSE00003888986	33694924	33695085
ENSE00003889195	33687226	33687327
ENSE00003889225	33657932	33658018
ENSE00003889297	33670325	33670576
ENSE00003889304	33665835	33665976
ENSE00003889311	33671165	33671306
ENSE00003889593	33693545	33693705
ENSE00003889677	33686053	33686253
ENSE00003889845	33678421	33678543
ENSE00003890346	33686409	33686519
ENSE00003890395	33684774	33684943
ENSE00003890639	33692728	33692893
ENSE00003890924	33662911	33663006
ENSE00003890956	33688656	33688781
ENSE00003891249	33684598	33684688
ENSE00003891340	33675691	33675856
ENSE00003891436	33679882	33680133
ENSE00003891451	33668974	33669156
ENSE00003891486	33683207	33683397
ENSE00003891568	33684357	33684465
ENSE00003891794	33677015	33677089
ENSE00003891989	33690034	33690198
ENSE00003892472	33688057	33688167
ENSE00003892507	33659021	33659119
ENSE00003892546	33689238	33689410
ENSE00003892573	33659466	33659549
ENSE00003892722	33685359	33685533
ENSE00003892724	33655766	33655887
ENSE00003892889	33674208	33674265
ENSE00003892925	33680555	33680680
ENSE00003893126	33690917	33691109
ENSE00003893376	33672029	33672228
ENSE00003893577	33682524	33682644
ENSE00003893908	33687009	33687104
ENSE00003893970	33685643	33685827
ENSE00003894272	33673591	33673720
ENSE00003894386	33665053	33665213
ENSE00003894421	33640484	33640554
ENSE00003894593	33691615	33691719
ENSE00003894734	33663738	33663880
ENSE00003894801	33667792	33667964
ENSE00003894840	33677504	33677629
ENSE00003894858	33668515	33668634
ENSE00003895050	33680329	33680454
ENSE00003895169	33662528	33662674
ENSE00003895276	33664870	33664969
ENSE00003895468	33667129	33667290
ENSE00003895578	33678639	33678839
ENSE00003895609	33658670	33658828
ENSE00003895902	33687478	33687564
ENSE00003896022	33670671	33670815
ENSE00003896031	33691801	33691928
ENSE00003896080	33676768	33676932
ENSE00003896202	33684020	33684168

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 97.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.6707 / max 273.9935, expressed in 1623 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67320	18.9316	1606
67321	1.4301	736
67322	0.5040	343
67323	0.3998	239
67324	0.2952	163
67319	0.1101	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	97.51	gold quality
pylorus	UBERON:0001166	96.69	gold quality
upper arm skin	UBERON:0004263	96.36	gold quality
trigeminal ganglion	UBERON:0001675	96.22	gold quality
sural nerve	UBERON:0015488	95.58	gold quality
upper leg skin	UBERON:0004262	95.41	gold quality
olfactory bulb	UBERON:0002264	95.19	gold quality
left lobe of thyroid gland	UBERON:0001120	94.70	gold quality
dorsal root ganglion	UBERON:0000044	94.69	gold quality
right lobe of thyroid gland	UBERON:0001119	94.59	gold quality
ileal mucosa	UBERON:0000331	94.50	gold quality
cardia of stomach	UBERON:0001162	94.46	gold quality
skin of abdomen	UBERON:0001416	94.34	gold quality
skin of leg	UBERON:0001511	94.12	gold quality
thyroid gland	UBERON:0002046	94.11	gold quality
gingival epithelium	UBERON:0001949	93.95	gold quality
tibial nerve	UBERON:0001323	93.94	gold quality
zone of skin	UBERON:0000014	93.77	gold quality
nasal cavity epithelium	UBERON:0005384	93.38	gold quality
epithelium of nasopharynx	UBERON:0001951	93.34	gold quality
endometrium epithelium	UBERON:0004811	93.33	gold quality
pancreatic ductal cell	CL:0002079	93.32	gold quality
colonic mucosa	UBERON:0000317	93.22	gold quality
lower lobe of lung	UBERON:0008949	93.21	gold quality
hair follicle	UBERON:0002073	93.18	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.71	gold quality
trachea	UBERON:0003126	92.53	gold quality
gingiva	UBERON:0001828	92.47	gold quality
synovial joint	UBERON:0002217	92.46	gold quality
corpus epididymis	UBERON:0004359	92.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.50

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NEUROD2

miRNA regulators (miRDB)

42 targeting ITPR3, 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-4481	100.00	66.42	1669
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-4473	98.89	69.10	652
HSA-MIR-1227-5P	98.65	65.32	1549

Literature-anchored findings (GeneRIF, showing 40)

• IP3R3 may be a prerequisite for secretion of an enzyme, such as protease, in gastric cancer cells; results indicate that IP3R3 may be specifically involved in gastric cancer peritoneal dissemination (PMID:14666665)
• differential expression of the IP(3)R subtype is critical for various forms of Ca(2+) signaling, and, particularly, IP(3)R1 and IP(3)R3 have opposite roles in generating Ca(2+) oscillations (PMID:14707143)
• The estimated population-attributable risk of 21.6% suggests that variation within ITPR3 reflects an important contribution to type 1 diabetes in Sweden. (PMID:16960798)
• Anti-IP(3)R1 antibodies were present in 48.6% of primary Sjogren’s syndrome and in 3.0% of normal healthy subjects. (PMID:17437169)
• IP3R3 is present in the paranodal regions of the nodes in the sciatic nerve. (PMID:17496801)
• A functional single nucleotide polymorphism in the NKX2.5-binding site of ITPR3 promoter is associated with susceptibility to systemic lupus erythematosus (PMID:18219441)
• the ankyrin-binding site is located on the cytoplasmic face of the InsP(3) receptor, thus validating the feasibility of in vivo ankyrin-InsP(3) receptor interactions. (PMID:18275062)
• The association between type 1 diabetes and the ITPR3 gene polymorphism due to linkage disequilibrium with HLA class II. (PMID:18340361)
• In this review, by sensing sequential binding of IP3 and calcium ions, the IP3 receptor acts as a coincidence detector that associates parallel fiber inputs with climbing fiber inputs. (PMID:18434505)
• sigma-1R overexpression drives sigma agonist-independent dissociation of ANK 220 from IP3R-3, resulting in activation (PMID:18539593)
• the agonist-induced clustering of IP(3)R is triggered by IP(3) binding, rather than Ca(2+) elevation. (PMID:18544901)
• May play a role in calcium-dependent nuclear processes. (PMID:18586264)
• IP3-mediated sensitization requires IP3 receptor binding to a TRPV4 C-terminal domain that overlaps with a previously described calmodulin-binding site (PMID:18826956)
• Inability of the T-cell receptors in TCR transgenic mice to trigger calcium mobilization may be due to the insufficient level of inositol 1,4,5-triphosphate receptor (IP3) type 3 to initiate the release of calcium from intracellular stores. (PMID:19050248)
• Caveolin-1 scaffold domain interacts with TRPC1 and IP3R3 to regulate Ca2+ store release-induced Ca2+ entry in endothelial cells. (PMID:19052258)
• Results demonstrate the importance of the InsP3 receptor-mutant huntingtin protein association for the pathogenesis of Huntington’s disease and as a potential therapeutic target for Huntington’s disease. (PMID:19193873)
• Data show that the BH4 domain mediates interaction of Bcl-2 with the inositol 1,4,5-trisphosphate (IP3) receptor on the endoplasmic reticulum. (PMID:19706527)
• Findings suggest IP(3)R3 as a novel therapeutic target and identify caffeine as a possible adjunct therapy to slow invasive growth of glioblastoma. (PMID:20103623)
• 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)
• results of this study suggest that the rs2229634 SNP in the ITPR3 gene is associated with the risk of coronary artery aneurysm formation in Taiwanese Kawasaki disease patients (PMID:20618519)
• inositol 145-triphosphate receptor type 3 becomes expressed in colon cancer, and its expression level is directly related to aggressiveness of the tumor (PMID:21075448)
• the critical region of KRAP protein for the regulation of IP(3)R was determined. (PMID:21501587)
• Ins(1,4,5)P3R-mediated Ca2+ signaling was critical for starvation-induced autophagy stimulation. (PMID:22082873)
• The study provides biochemical evidence of the interaction between FKBP12 and RYR1, RYR3 and IP3R. (PMID:22100703)
• The presence of isoform III of inositol 1,4,5-trisphosphate receptor is the key point of Akt activity on calcium-mediated apoptosis. (PMID:22552281)
• in human pulmonary fibroblasts, PDGF acts through IP3-induced Ca(2+)-release to trigger Ca(2+) waves, which in turn modulate gene expression of several matrix proteins. (PMID:23618877)
• 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)
• A molecular and functional link between BKCa channel and IP3R3 in cancer cells as an important mechanism for tumor cell proliferation. (PMID:23992640)
• It mediate calcium release from intracellular calcium stores such as the ER into the cytoplasm. (review) (PMID:24285081)
• Physiologically relevant reactive oxygen species controls cytoplasmic and mitochondrial calcium transport through IP3 receptors. (PMID:24469450)
• miR-506 is a regulator of InsP3R3 expression and InsP3R3-mediated Ca2+ signaling and secretion. (PMID:25378392)
• The transcription factor NRF2 binds to the promoter of ITPR3 to inhibit its expression in cholangiocytes, leading to reduced calcium signaling and bile duct secretion. (PMID:25796361)
• 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)
• Suggest that AT haplotype in the ITPR3 gene may serve as a potential marker for genetic susceptibility to cervical squamous cell carcinoma risk in Taiwanese women. (PMID:28036301)
• PTEN counteracts FBXL2 to promote IP3R3- and Ca(2+)-mediated apoptosis limiting tumour growth (PMID:28614300)
• BAP1 regulates IP3R3-mediated Ca(2+) flux to mitochondria suppressing cell transformation (PMID:28614305)
• TOM70, but not TOM20, clusters in distinct OMM foci, frequently overlapping with sites in which the endoplasmic reticulum (ER) contacts mitochondria. Functionally, TOM70 depletion specifically impairs inositol trisphosphates (IP3)-linked ER to mitochondria Ca(2+) transfer. This phenomenon is dependent on the capacity of TOM70 to interact with IP3-receptors and favor their functional recruitment close to mitochondria. (PMID:29395920)
• Data demonstrated that IP3R3 is able to modulate intracellular Ca(2+) availability and to coordinate the remodeling of profilin cytoskeleton organization through the ARHGAP18/RhoA/mDia1/FAK pathway. (PMID:29630900)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	itpr3	ENSDARG00000061741
mus_musculus	Itpr3	ENSMUSG00000042644
rattus_norvegicus	Itpr3	ENSRNOG00000052795
drosophila_melanogaster	RyR	FBGN0011286
caenorhabditis_elegans		WBGENE00006801

Paralogs (5): ITPR2 (ENSG00000123104), ITPR1 (ENSG00000150995), RYR1 (ENSG00000196218), RYR2 (ENSG00000198626), RYR3 (ENSG00000198838)

Protein

Protein identifiers

Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 — Q14573 (reviewed: Q14573)

Alternative names: IP3 receptor isoform 3, Type 3 inositol 1,4,5-trisphosphate receptor

All UniProt accessions (1): Q14573

UniProt curated annotations — full annotation on UniProt →

Function. Inositol 1,4,5-trisphosphate-gated calcium channel that, upon 1D-myo-inositol 1,4,5-trisphosphate binding, transports calcium from the endoplasmic reticulum lumen to cytoplasm, thus releasing the intracellular calcium and therefore participates in cellular calcium ion homeostasis. 1D-myo-inositol 1,4,5-trisphosphate binds to the ligand-free channel without altering its global conformation, yielding the low-energy resting state, then progresses through resting-to preactivated transitions to the higher energy preactivated state, which increases affinity for calcium, promoting binding of the low basal cytosolic calcium at the juxtamembrane domain (JD) site, favoring the transition through the ensemble of high-energy intermediate states along the trajectory to the fully-open activated state. Upon opening, releases calcium in the cytosol where it can bind to the low-affinity cytoplasmic domain (CD) site and stabilizes the inhibited state to terminate calcium release.

Subunit / interactions. Homotetramer. Homodimer. Interacts with TRPC1, TRPC3 and TRPC4. Interacts with TRPV4. Interacts with SIGMAR1. Interacts with PML and AKT1. Interacts with IRAG2 (via coiled-coil domain). Interacts with CABP1. Interacts with TMBIM4/LFG4. Interacts with CEMIP. Interacts with TESPA1. Interacts with TMEM203. Interacts with BOK; regulates ITPR3 expression. Interacts with BCL2L10. Interacts with CHGA and CHGB.

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

Tissue specificity. Expressed in intestinal crypt and villus epithelial cells.

Post-translational modifications. Phosphorylated by AKT1 on serine and/or threonine residues.

Disease relevance. Charcot-Marie-Tooth disease, demyelinating, type 1J (CMT1J) [MIM:620111] An autosomal dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. The disease is caused by variants affecting the gene represented in this entry. Immunodeficiency 133 with ectodermal dysplasia with or without peripheral neuropathy (IMD133) [MIM:621254] An autosomal dominant multisystem disorder primarily characterized by combined immunodeficiency or common variable immunodeficiency, and incompletely penetrant ectodermal dysplasia. Additional variable features include motor and speech developmental delay, poor growth, and demyelinating or axonal peripheral neuropathy. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inositol 1,4,5-trisphosphate-gated calcium channel is regulated by cytosolic calcium in a biphasic manner. At low concentrations, cytosolic calcium binds at a high-affinity juxtamembrane domain (JD) calcium binding site, allowing ITPR3 to activate by escaping a low-energy resting state through an ensemble of preactivated states. At high cytosolic calcium concentrations, ITPR3 preferentially enters an inhibited state stabilized by calcium binding at a second, low-affinity cytoplasmic domain (CD) calcium binding site.

Domain organisation. Composed of a large N-terminal cytoplasmic domain (CD) followed by a juxtamembrane domain (JD) and a transmembrane domain (TMD).

Similarity. Belongs to the InsP3 receptor family.

RefSeq proteins (1): NP_002215* (*=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
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 (82 total): binding site 29, sequence variant 15, sequence conflict 8, topological domain 7, modified residue 7, transmembrane region 6, domain 5, region of interest 3, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

24 structures.

PDB	Method	Resolution (Å)
8TKG	ELECTRON MICROSCOPY	2.5
8TK8	ELECTRON MICROSCOPY	2.7
7T3P	ELECTRON MICROSCOPY	3.2
8TKF	ELECTRON MICROSCOPY	3.2
8TLA	ELECTRON MICROSCOPY	3.2
7T3Q	ELECTRON MICROSCOPY	3.3
8TL9	ELECTRON MICROSCOPY	3.3
6DQN	ELECTRON MICROSCOPY	3.33
7T3R	ELECTRON MICROSCOPY	3.4
6DQJ	ELECTRON MICROSCOPY	3.49
8TKH	ELECTRON MICROSCOPY	3.5
8TKE	ELECTRON MICROSCOPY	3.6
8TKI	ELECTRON MICROSCOPY	3.6
7T3U	ELECTRON MICROSCOPY	3.7
8TKD	ELECTRON MICROSCOPY	3.7
6UQK	ELECTRON MICROSCOPY	3.77
7T3T	ELECTRON MICROSCOPY	3.8
6DQV	ELECTRON MICROSCOPY	3.82
6DRC	ELECTRON MICROSCOPY	3.92
6DRA	ELECTRON MICROSCOPY	3.96
6DQS	ELECTRON MICROSCOPY	4.12
6DR2	ELECTRON MICROSCOPY	4.33
6DR0	ELECTRON MICROSCOPY	4.47
6DQZ	ELECTRON MICROSCOPY	6.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14573-F1	74.04	0.03

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 (29): 266; 268; 269; 270; 503; 507; 510; 567; 568; 569; 743; 1122 …

Post-translational modifications (7): 916, 934, 1813, 1832, 1834, 2609, 2670

Disulfide bonds (1): 2455–2461

Function

Pathways and Gene Ontology

Reactome pathways

52 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-9717207	Sensory perception of sweet, bitter, and umami (glutamate) taste
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

MSigDB gene sets: 463 (showing top): GOBP_MEMORY, MODULE_52, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_PROTEIN_HOMOTETRAMERIZATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, JAEGER_METASTASIS_DN, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GCANCTGNY_MYOD_Q6, GOBP_PLATELET_ACTIVATION, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, LHX3_01, FOXO1_01

GO Biological Process (19): G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of cytosolic calcium ion concentration (GO:0007204), memory (GO:0007613), platelet activation (GO:0030168), sensory perception of taste (GO:0050909), sensory perception of bitter taste (GO:0050913), sensory perception of sweet taste (GO:0050916), sensory perception of umami taste (GO:0050917), release of sequestered calcium ion into cytosol (GO:0051209), protein homotetramerization (GO:0051289), response to calcium ion (GO:0051592), calcium ion homeostasis (GO:0055074), long-term synaptic potentiation (GO:0060291), 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 (12): inositol hexakisphosphate binding (GO:0000822), inositol 1,4,5-trisphosphate-gated calcium channel activity (GO:0005220), calcium ion binding (GO:0005509), ATP binding (GO:0005524), zinc ion binding (GO:0008270), intracellularly gated calcium channel activity (GO:0015278), phosphatidylinositol binding (GO:0035091), inositol 1,3,4,5 tetrakisphosphate binding (GO:0043533), inositol 1,4,5 trisphosphate binding (GO:0070679), monoatomic ion channel activity (GO:0005216), calcium channel activity (GO:0005262), protein binding (GO:0005515)

GO Cellular Component (19): nuclear outer membrane (GO:0005640), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), brush border (GO:0005903), membrane (GO:0016020), sarcoplasmic reticulum (GO:0016529), transport vesicle membrane (GO:0030658), secretory granule membrane (GO:0030667), platelet dense tubular network membrane (GO:0031095), neuronal cell body (GO:0043025), signaling receptor complex (GO:0043235), apical part of cell (GO:0045177), cytoplasmic side of endoplasmic reticulum membrane (GO:0098554), nucleus (GO:0005634), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-19 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
Sensory perception of taste	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anion binding	4
cellular anatomical structure	4
sensory perception of taste	3
alcohol binding	3
bounding membrane of organelle	3
transport	2
nuclear outer membrane-endoplasmic reticulum membrane network	2
nuclear lumen	2
cytoplasm	2
intracellular membrane-bounded organelle	2
cytoplasmic vesicle membrane	2
G protein-coupled receptor activity	1
signal transduction	1
regulation of biological quality	1
learning or memory	1
cell activation	1
blood coagulation	1
sensory perception of chemical stimulus	1
intercellular transport	1
calcium ion transmembrane import into cytosol	1
protein homooligomerization	1
protein tetramerization	1
response to metal ion	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
regulation of synaptic plasticity	1
positive regulation of synaptic transmission	1
metal ion transport	1
intracellular signaling cassette	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	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
transition metal ion binding	1

Protein interactions and networks

STRING

2650 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITPR3	VDAC1	P21796	996
ITPR3	HSPA9	P30036	995
ITPR3	BCL2	P10415	992
ITPR3	BECN1	Q14457	983
ITPR3	CYCS	P00001	978
ITPR3	TRPC1	P48995	962
ITPR3	AKT1	P31749	955
ITPR3	ANK2	Q01484	952
ITPR3	TOMM70	O94826	947
ITPR3	BCL2L1	Q07817	941
ITPR3	SIGMAR1	Q99720	910
ITPR3	PPIF	P30405	905
ITPR3	STIM1	Q13586	894
ITPR3	MCU	Q8NE86	883
ITPR3	CALR	P27797	876

IntAct

172 interactions, top by confidence:

A	B	Type	Score
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
COMMD4	VPS26C	psi-mi:“MI:0914”(association)	0.730
BAP1	ITPR3	psi-mi:“MI:0915”(physical association)	0.640
BAP1	ITPR3	psi-mi:“MI:2364”(proximity)	0.640
BAP1	ITPR3	psi-mi:“MI:0403”(colocalization)	0.640
ITPR3	BAP1	psi-mi:“MI:0915”(physical association)	0.640
BAP1	ITPR3	psi-mi:“MI:0204”(deubiquitination reaction)	0.640
STIM2	PRKAB2	psi-mi:“MI:0914”(association)	0.640
ITPR3	TRPC3	psi-mi:“MI:0915”(physical association)	0.590
TRPC3	ITPR3	psi-mi:“MI:0915”(physical association)	0.590
FRMD1	A2ML1	psi-mi:“MI:0914”(association)	0.530
TAFA4	NRP1	psi-mi:“MI:0914”(association)	0.530
FGL2	PCNT	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
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530

BioGRID (313): ITPR3 (Biochemical Activity), ITPR3 (Affinity Capture-MS), ITPR3 (Affinity Capture-MS), ITPR3 (Affinity Capture-MS), ITPR3 (Affinity Capture-MS), ITPR3 (Affinity Capture-MS), ITPR3 (Affinity Capture-MS), ITPR3 (Affinity Capture-MS), ITPR3 (Affinity Capture-MS), ITPR3 (Affinity Capture-MS), ITPR3 (Affinity Capture-MS), ITPR3 (Affinity Capture-MS), ITPR3 (Affinity Capture-MS), ITPR3 (Affinity Capture-MS), ITPR3 (Affinity Capture-MS)

ESM2 similar proteins: A1L3F5, A2AHJ4, A6NHR9, A8K855, A9JRL3, B1AY13, O02697, O75165, O75717, P29993, P29995, P48736, P59328, P60670, Q0E908, Q14571, Q14573, Q21029, Q5R8B7, Q5ZLG9, Q69ZX6, Q6AZT7, Q6DCF6, Q6DD21, Q6DDI6, Q6DEY8, Q6GLR7, Q6P5D8, Q6RI45, Q7Z494, Q80T23, Q812E4, Q8BGQ1, Q8IY22, Q8TAT6, Q8TDW5, Q8VDY4, Q8WN96, Q8WSR4, Q95JW3

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 190 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
G-protein mediated events	6	14.9×	9e-04
DAG and IP3 signaling	6	14.5×	9e-04
Calmodulin induced events	5	14.5×	2e-03
CaM pathway	5	14.5×	2e-03
Ca-dependent events	5	14.1×	2e-03
Phase 0 - rapid depolarisation	5	13.2×	2e-03
Opioid Signalling	6	12.2×	1e-03
PLC beta mediated events	6	12.2×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of protein localization to plasma membrane	5	20.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	399
Likely benign	77
Benign	146

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1722508	NM_002224.4(ITPR3):c.1843G>A (p.Val615Met)	Pathogenic
4057194	NM_002224.4(ITPR3):c.586G>A (p.Ala196Thr)	Pathogenic
4057195	NM_002224.4(ITPR3):c.7517T>A (p.Ile2506Asn)	Pathogenic
3358903	NM_002224.4(ITPR3):c.3058+2T>C	Likely pathogenic
3664150	NM_002224.4(ITPR3):c.7571G>A (p.Arg2524His)	Likely pathogenic

SpliceAI

9964 predictions. Top by Δscore:

Variant	Effect	Δscore
6:33640478:CCCCA:C	acceptor_loss	1.0000
6:33640479:CCCA:C	acceptor_loss	1.0000
6:33640480:CCA:C	acceptor_loss	1.0000
6:33640481:CAGGC:C	acceptor_loss	1.0000
6:33640482:A:AG	acceptor_gain	1.0000
6:33640482:A:T	acceptor_loss	1.0000
6:33640482:AG:A	acceptor_gain	1.0000
6:33640482:AGGCT:A	acceptor_gain	1.0000
6:33640483:G:GA	acceptor_gain	1.0000
6:33640483:GG:G	acceptor_gain	1.0000
6:33640483:GGC:G	acceptor_gain	1.0000
6:33640483:GGCT:G	acceptor_gain	1.0000
6:33640483:GGCTG:G	acceptor_gain	1.0000
6:33640552:GTG:G	donor_gain	1.0000
6:33655764:A:AG	acceptor_gain	1.0000
6:33655764:AGACT:A	acceptor_gain	1.0000
6:33655765:G:GG	acceptor_gain	1.0000
6:33655765:GACT:G	acceptor_gain	1.0000
6:33655765:GACTG:G	acceptor_gain	1.0000
6:33655884:GCAG:G	donor_gain	1.0000
6:33655887:GGTA:G	donor_loss	1.0000
6:33655888:G:GG	donor_gain	1.0000
6:33657917:T:TA	acceptor_gain	1.0000
6:33657919:T:TA	acceptor_gain	1.0000
6:33657921:T:TA	acceptor_gain	1.0000
6:33657925:T:TA	acceptor_gain	1.0000
6:33657927:T:TA	acceptor_gain	1.0000
6:33657928:GCAGC:G	acceptor_loss	1.0000
6:33657929:CAGCA:C	acceptor_loss	1.0000
6:33657930:A:AG	acceptor_gain	1.0000

AlphaMissense

17788 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:33655805:C:A	A67D	1.000
6:33655883:T:C	L93P	1.000
6:33657938:G:C	A97P	1.000
6:33658671:T:C	L124P	1.000
6:33658698:T:C	L133P	1.000
6:33658781:T:A	W161R	1.000
6:33658781:T:C	W161R	1.000
6:33659493:T:A	W219R	1.000
6:33659493:T:C	W219R	1.000
6:33662544:T:A	L243Q	1.000
6:33662544:T:C	L243P	1.000
6:33662546:T:C	F244L	1.000
6:33662547:T:C	F244S	1.000
6:33662548:C:A	F244L	1.000
6:33662548:C:G	F244L	1.000
6:33662567:T:C	F251L	1.000
6:33662568:T:C	F251S	1.000
6:33662568:T:G	F251C	1.000
6:33662569:C:A	F251L	1.000
6:33662569:C:G	F251L	1.000
6:33662571:T:C	L252P	1.000
6:33662610:T:C	L265P	1.000
6:33662634:C:A	A273D	1.000
6:33662663:T:A	W283R	1.000
6:33662663:T:C	W283R	1.000
6:33662665:G:C	W283C	1.000
6:33662665:G:T	W283C	1.000
6:33662950:T:A	W300R	1.000
6:33662950:T:C	W300R	1.000
6:33662969:T:C	F306S	1.000

dbSNP variants (sampled 300 via entrez): RS1000024498 (6:33689519 C>T), RS1000024971 (6:33689842 C>T), RS1000072251 (6:33648972 T>C), RS1000253697 (6:33683757 G>A), RS1000269494 (6:33685042 G>C), RS1000385494 (6:33641067 C>G,T), RS1000434344 (6:33678233 C>G), RS1000460536 (6:33661683 G>C), RS1000555615 (6:33668105 G>C), RS1000607839 (6:33667801 G>A), RS1000660770 (6:33695855 C>G,T), RS1000699387 (6:33620134 A>AACAC), RS1000760758 (6:33631048 C>A), RS1000817345 (6:33644484 C>A,G,T), RS1000828651 (6:33644206 G>A)

Disease associations

OMIM: gene MIM:147267 | disease phenotypes: MIM:621254, MIM:620111, MIM:192500, MIM:222100

GenCC curated gene-disease

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease, demyelinating, type 1J	Definitive	Autosomal dominant
combined immunodeficiency	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease, demyelinating, type 1J	Definitive	AD

Mondo (5): immunodeficiency 133 with ectodermal dysplasia with or without peripheral neuropathy (MONDO:0979570), Charcot-Marie-Tooth disease, demyelinating, type 1J (MONDO:0859311), familial long QT syndrome (MONDO:0019171), type 1 diabetes mellitus (MONDO:0005147), combined immunodeficiency (MONDO:0015131)

Orphanet (3): Romano-Ward syndrome (Orphanet:101016), Congenital long QT syndrome (Orphanet:768), NON RARE IN EUROPE: Diabetes mellitus type 1 (Orphanet:243377)

HPO phenotypes

158 total (30 of 158 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000175	Cleft palate
HP:0000252	Microcephaly
HP:0000265	Mastoiditis
HP:0000365	Hearing impairment
HP:0000403	Recurrent otitis media
HP:0000668	Hypodontia
HP:0000680	Delayed eruption of primary teeth
HP:0000691	Microdontia
HP:0000698	Conical tooth
HP:0000717	Autism
HP:0000750	Delayed speech and language development
HP:0000768	Pectus carinatum
HP:0000939	Osteoporosis
HP:0000952	Jaundice
HP:0000958	Dry skin
HP:0000964	Eczematoid dermatitis
HP:0000966	Hypohidrosis
HP:0000967	Petechiae
HP:0000968	Ectodermal dysplasia
HP:0000988	Skin rash
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001271	Polyneuropathy
HP:0001284	Areflexia
HP:0001287	Meningitis
HP:0001288	Gait disturbance

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000426_5	Obesity (extreme)	1.000000e-06
GCST000703_3	Phosphorus levels	1.000000e-11
GCST002045_5	Educational attainment	3.000000e-07
GCST002094_5	Crohn’s disease	1.000000e-08
GCST004068_50	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	5.000000e-07
GCST005038_65	Allergic disease (asthma, hay fever or eczema)	4.000000e-13
GCST005951_153	Body mass index	5.000000e-09
GCST006920_1	Regular attendance at a gym or sports club	4.000000e-08
GCST007062_2	Hodgkin’s lymphoma	2.000000e-10
GCST007126_1	Multiple sclerosis and body mass index (pleiotropy)	2.000000e-07
GCST007656_5	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	3.000000e-15
GCST008919_7	Asthma and attention deficit hyperactivity disorder	4.000000e-08
GCST011436_2	Total carotid plaque area (excess vs minimal atherosclerosis)	3.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004861	phosphorus measurement
EFO:0004784	self reported educational attainment
EFO:0004340	body mass index
EFO:0009592	social interaction measurement
EFO:0006501	carotid plaque build

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003922	Diabetes Mellitus, Type 1	C18.452.394.750.124; C19.246.267; C20.111.327

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111451 (PROTEIN FAMILY), CHEMBL3904 (SINGLE PROTEIN)

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

19 potent at pChembl≥5 of 22 total, top 19 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.93	Kd	1.17	nM	CHEMBL297496
8.54	IC50	2.9	nM	CHEMBL23552
8.35	IC50	4.43	nM	INS(1,4,5)P3
8.21	IC50	6.1	nM	CHEMBL283791
7.85	IC50	14	nM	CHEMBL3349691
7.58	IC50	26.5	nM	CHEMBL3349691
7.47	IC50	33.5	nM	INS(1,4,5)P3
7.36	IC50	44	nM	CHEMBL281132
7.28	IC50	52	nM	INS(1,4,5)P3
6.89	EC50	130	nM	CHEMBL1161456
6.76	IC50	172	nM	CHEMBL1160286
6.73	Kd	188	nM	CHEMBL46273
6.71	Kd	195	nM	INS(1,4,5)P3
6.70	IC50	200	nM	INS(1,4,5)P3
6.68	EC50	210	nM	CHEMBL1161466
6.39	EC50	410	nM	CHEMBL1161466
6.37	IC50	430	nM	CHEMBL282059
6.21	IC50	620	nM	CHEMBL23050
5.95	Kd	1116	nM	CHEMBL297235

PubChem BioAssay actives

15 with measured affinity, of 15 total; 11 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[4-[[4-(dimethylamino)phenyl]-[4-[3-[hydroxy-[(1R,2R,3S,4R,5R,6S)-2,3,6-trihydroxy-4,5-diphosphonooxycyclohexyl]oxyphosphoryl]oxypropylcarbamoyl]phenyl]methylidene]cyclohexa-2,5-dien-1-ylidene]-dimethylazanium chloride	92897: Dissociation constant of compound was measured in IP3-binding domain(IBD) of human Inositol 1,4,5-trisphosphate receptor at pH 7.4	kd	0.0012	uM
[(1R,2S,4S,5S)-2,4-dihydroxy-3,5,6-triphosphonooxycyclohexyl] dihydrogen phosphate	93054: Inhibition of Ins(1,3,4,5)P4-PtdIns(3,4,5)P3-specific receptor from Pig cerebellum membrane	ic50	0.0029	uM
[(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
[(1R,2S,4S,5S)-2,3,4-trihydroxy-5,6-diphosphonooxycyclohexyl] dihydrogen phosphate	93054: Inhibition of Ins(1,3,4,5)P4-PtdIns(3,4,5)P3-specific receptor from Pig cerebellum membrane	ic50	0.0061	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
[(1S,3R,4R,6R)-4,5,6-trihydroxy-2-methyl-2,3-diphosphonooxycyclohexyl] dihydrogen phosphate	93054: Inhibition of Ins(1,3,4,5)P4-PtdIns(3,4,5)P3-specific receptor from Pig cerebellum membrane	ic50	0.0440	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
(6’-hydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-3’-yl) N-[3-[hydroxy-[(1R,2R,3S,4R,5R,6S)-2,3,6-trihydroxy-4,5-diphosphonooxycyclohexyl]oxyphosphoryl]oxypropyl]carbamate	92897: Dissociation constant of compound was measured in IP3-binding domain(IBD) of human Inositol 1,4,5-trisphosphate receptor at pH 7.4	kd	0.1880	uM
[(1R,2R,3S,4R,5S,6S)-2,3-dihydroxy-4,5,6-triphosphonooxycyclohexyl] dihydrogen phosphate	93054: Inhibition of Ins(1,3,4,5)P4-PtdIns(3,4,5)P3-specific receptor from Pig cerebellum membrane	ic50	0.4300	uM
[(1S,2S,3R,4S,5R,6R)-2,3-dihydroxy-4,5,6-triphosphonooxycyclohexyl] dihydrogen phosphate	93054: Inhibition of Ins(1,3,4,5)P4-PtdIns(3,4,5)P3-specific receptor from Pig cerebellum membrane	ic50	0.6200	uM
3-aminopropyl [(1R,2R,3S,4R,5R,6S)-2,3,6-trihydroxy-4,5-diphosphonooxycyclohexyl] hydrogen phosphate	92897: Dissociation constant of compound was measured in IP3-binding domain(IBD) of human Inositol 1,4,5-trisphosphate receptor at pH 7.4	kd	1.1160	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	6
Benzo(a)pyrene	increases expression, affects methylation, decreases methylation	4
Tretinoin	decreases expression	3
Cyclosporine	increases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
perfluorooctanoic acid	affects cotreatment, affects expression, increases expression	2
perfluorooctane sulfonic acid	affects expression, affects cotreatment, increases expression	2
entinostat	increases expression, affects cotreatment	2
Hydrogen Peroxide	affects expression	2
Vitamin K 3	affects expression	2
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, affects methylation, decreases methylation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression, increases expression	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	decreases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
aflatoxin B2	increases methylation	1
nickel sulfate	increases expression	1
coumarin	decreases phosphorylation	1
vanadyl sulfate	increases expression	1
1-aminomethylphosphonic acid	decreases expression	1
tamibarotene	decreases expression	1

ChEMBL screening assays

11 unique, capped per target: 9 binding, 2 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

14 cell lines: 7 cancer cell line, 7 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7XQ	Abcam Raji ITPR3 KO	Cancer cell line	Male
CVCL_B9YF	Abcam THP-1 ITPR3 KO	Cancer cell line	Male
CVCL_C7A7	Abcam PC-3 ITPR3 KO	Cancer cell line	Male
CVCL_D7SW	Ubigene A-549 ITPR3 KO	Cancer cell line	Male
CVCL_D8NN	Ubigene HCT 116 ITPR3 KO	Cancer cell line	Male
CVCL_D9HN	Ubigene HEK293 ITPR3 KO	Transformed cell line	Female
CVCL_E0FS	Ubigene HeLa ITPR3 KO	Cancer cell line	Female
CVCL_HB82	HEK-3KO	Transformed cell line	Female
CVCL_HB83	HEKR1	Transformed cell line	Female
CVCL_HB84	HEKR2	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT00145353	PHASE4	UNKNOWN	Insulin NovoRapid Versus Actrapid in Treatment of Type 1 Diabetic Patients During Daily Adjustment of Insulin Dose
NCT00145379	PHASE4	COMPLETED	The Effect of Metformin in Overweight Patients With Dysregulated Type 1 Diabetes Mellitus
NCT00206401	PHASE4	COMPLETED	Lantus in the Treatment of Type 1 Diabetes Children
NCT00276393	PHASE4	COMPLETED	Treatment Trial Evaluating Long Acting Insulin in Type 1 Diabetes
NCT00291772	PHASE4	COMPLETED	Continuous Subcutaneous Infusion of Pramlintide and Insulin
NCT00315952	PHASE4	COMPLETED	Study to Estimate the Effects of Inhaled Versus Intravenous (IV) Infusion of Human Insulin in Subjects With Type 1 Diabetes
NCT00340613	PHASE4	COMPLETED	Lunch Time Insulin Injection by School Nurse for Poorly Controlled Diabetes
NCT00346996	PHASE4	COMPLETED	Insulin Analogues and Severe Hypoglycaemia
NCT00360984	PHASE4	COMPLETED	Prevention of Severe Hypoglycemia in Type 1 Diabetes
NCT00372086	PHASE4	COMPLETED	Rosiglitazone and Insulin in T1DM Adolescents
NCT00442767	PHASE4	COMPLETED	Post-meal Insulin Dosing With Adjuvant Pre-meal Pramlintide in Children With Type 1 Diabetes Mellitus
NCT00453934	PHASE4	TERMINATED	Patient Preference of h-Patch vs. Pen or Needle/Syringe as Insulin Administration Device
NCT00461331	PHASE4	COMPLETED	Comparison of Insulins Aspart and Lispro in Insulin Pumps
NCT00472875	PHASE4	UNKNOWN	Do Sulphonylureas Preserve Cortical Function During Hypoglycaemia?
NCT00497536	PHASE4	COMPLETED	Pharmacokinetics of IAsp Following CSII in Patients With T1DM
NCT00502138	PHASE4	COMPLETED	A Pilot Study of Continuous Subcutaneous Pramlintide Infusion Therapy in Patients With Type 1 Diabetes
NCT00505882	PHASE4	WITHDRAWN	Efficacy of Pramlintide on Prevention of Weight Gain Early Onset of Type 1 Diabetes
NCT00530023	PHASE4	COMPLETED	Feasibility Study for Training Pump Naïve Subjects To Use The Paradigm® System And Evaluate Effectiveness
NCT00542399	PHASE4	COMPLETED	Comparing the Metabolic Control of Once to Twice-daily Insulin Detemir Injections
NCT00564395	PHASE4	COMPLETED	Detemir: Role in Type 1 Diabetes
NCT00814476	PHASE4	COMPLETED	The Effects of Regular Home Use Vs Diabetic Team- Supported Use of the Medtronic CareLink Therapy Management System.
NCT00898534	PHASE4	COMPLETED	Effect of Immediate Hemoglobin A1c on Glycemic Control in Children With Type I Diabetes Mellitus
NCT00913497	PHASE4	COMPLETED	The Effect of Insulin Glulisine Compared With Insulin Aspart on Breakfast Post Prandial Glucose Levels in Prepubertal Children
NCT00978796	PHASE4	COMPLETED	Assessing Glucose Effects of Sitagliptin (Januvia) in Adult Patients With Type 1 Diabetes
NCT01019486	PHASE4	COMPLETED	Regadenoson Blood Flow in Type 1 Diabetes (RABIT1D)
NCT01235819	PHASE4	COMPLETED	Comparison Between GLP 1 Analogues and DPP 4 Inhibitors in Type 1 Diabetes Mellitus
NCT01269034	PHASE4	COMPLETED	New Onset Type 1 Diabetes: Role of Exenatide
NCT01269047	PHASE4	COMPLETED	Use of Exenatide and Pramlintide to Decrease Post-prandial Hyperglycemia
NCT01280682	PHASE4	COMPLETED	Immune Intervention With Rituximab to Preserve Beta Cell Function in Early Onset Type 1 Diabetes
NCT01331343	PHASE4	COMPLETED	Effectiveness Study of the Guardian RT in Type 1 Diabetics
NCT01351857	PHASE4	COMPLETED	Diabetes Care Management Compared to Standard Diabetes Care in Adolescents and Young Adults With Type 1 Diabetes
NCT01390480	PHASE4	COMPLETED	Effects of Vitamin D Supplementation in Subjects With New Onset of Type 1 Diabetes
NCT01400659	PHASE4	COMPLETED	Pizza-Salami Study in Children and Adolescents With Type 1 Diabetes
NCT01454700	PHASE4	COMPLETED	Effect of CSII and CGM on Progression of Late Diabetic Complications
NCT01488136	PHASE4	COMPLETED	Use of Diazoxide in Acute Hypoglycaemia
NCT01497912	PHASE4	COMPLETED	Treatment Effects of Atorvastatin on Hemostasis and Skin Microcirculation in Patients With Type 1 Diabetes