ITPR3 inositol 1,4,5-trisphosphate receptor type 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ITPR3provided by HGNC
Official Full Name: inositol 1,4,5-trisphosphate receptor type 3provided by HGNC
Primary source: HGNC:HGNC:6182
See related: Ensembl:ENSG00000096433 MIM:147267; AllianceGenome:HGNC:6182
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: IP3R; CMT1J; IP3R3; IP3R-3
Summary: 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. [provided by RefSeq, Aug 2010]
Expression: Broad expression in thyroid (RPKM 29.7), skin (RPKM 28.2) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6p21.31

Exon count:: 62

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (33621322..33696562)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (33442464..33517747)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (33589099..33664339)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A pleiotropic recurrent dominant ITPR3 variant causes a complex multisystemic disease.
Title: A pleiotropic recurrent dominant ITPR3 variant causes a complex multisystemic disease.
Disrupted Ca[2+] homeostasis and immunodeficiency in patients with functional IP3 receptor subtype 3 defects.
Title: Disrupted Ca(2+) homeostasis and immunodeficiency in patients with functional IP(3) receptor subtype 3 defects.
Inositol 1,4,5-trisphosphate receptor gene variants are related to the risk of breast cancer in a Chinese population.
Title: Inositol 1,4,5-trisphosphate receptor gene variants are related to the risk of breast cancer in a Chinese population.
Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) is overexpressed in cholangiocarcinoma and its expression correlates with S100 calcium-binding protein A4 (S100A4).
Title: Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) is overexpressed in cholangiocarcinoma and its expression correlates with S100 calcium-binding protein A4 (S100A4).
ITPR3 facilitates tumor growth, metastasis and stemness by inducing the NF-kB/CD44 pathway in urinary bladder carcinoma.
Title: ITPR3 facilitates tumor growth, metastasis and stemness by inducing the NF-ĸB/CD44 pathway in urinary bladder carcinoma.
Dominant mutations in ITPR3 cause Charcot-Marie-Tooth disease.
Title: Dominant mutations in ITPR3 cause Charcot-Marie-Tooth disease.
Potentially functional variants of HBEGF and ITPR3 in GnRH signaling pathway genes predict survival of non-small cell lung cancer patients.
Title: Potentially functional variants of HBEGF and ITPR3 in GnRH signaling pathway genes predict survival of non-small cell lung cancer patients.
STIM1 Deficiency Leads to Specific Down-Regulation of ITPR3 in SH-SY5Y Cells.
Title: STIM1 Deficiency Leads to Specific Down-Regulation of ITPR3 in SH-SY5Y Cells.
Type 3 Inositol 1,4,5-Trisphosphate Receptor is a Crucial Regulator of Calcium Dynamics Mediated by Endoplasmic Reticulum in HEK Cells.
Title: Type 3 Inositol 1,4,5-Trisphosphate Receptor is a Crucial Regulator of Calcium Dynamics Mediated by Endoplasmic Reticulum in HEK Cells.
Cryo-EM structure of human type-3 inositol triphosphate receptor reveals the presence of a self-binding peptide that acts as an antagonist.
Title: Cryo-EM structure of human type-3 inositol triphosphate receptor reveals the presence of a self-binding peptide that acts as an antagonist.

Submit: New GeneRIF Correction See all GeneRIFs (59)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Charcot-Marie-Tooth disease, demyelinating, type 1J MedGen: C5774249 OMIM: 620111 GeneReviews: Not available	not available
Diabetes mellitus type 1 MedGen: C0011854 OMIM: 222100 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Common body mass index-associated variants confer risk of extreme obesity. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common genetic variants associate with serum phosphorus concentration. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations. EBI GWAS Catalog EBI GWAS CatalogPubMed
GWAS of 126,559 individuals identifies genetic variants associated with educational attainment. EBI GWAS Catalog EBI GWAS CatalogPubMed
Hundreds of variants clustered in genomic loci and biological pathways affect human height. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of independent risk loci for Graves' disease within the MHC in the Japanese population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Pr55(Gag)	gag	IP3R differentially associates with HIV-1 wild-type Gag and P7L-Gag, indicating that Gag and IP3R are in proximity at the plasma membrane	PubMed
	gag	Inositol (1,4,5)-triphosphate receptor (IP3R) is required for efficient release of HIV-1 Gag in the presence or absence of TSG101 binding	PubMed
	gag	HIV-1 Gag co-localizes with IP3R-3 in plasma-membrane-proximal punctuate structures and plasma membrane	PubMed
	gag	SPRY-mediated inhibition of HIV-1 Gag release is repressed by IP3R	PubMed
Tat	tat	HIV-1 Tat induces release of calcium from inositol 1,4,5-triphosphate receptor-regulated stores in neurons and astrocytes, an effect that plays an important role in Tat-induced TNF-alpha production	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH93741 (e-PCR)
- UniSTS:89386

ha3079 (e-PCR)
- UniSTS:515639

SHGC-144717 (e-PCR)
- UniSTS:172374

RH46652 (e-PCR)
- UniSTS:24412

RH65340 (e-PCR)
- UniSTS:73834

STS-U01062 (e-PCR)
- UniSTS:72299

D6S2048 (e-PCR)
- UniSTS:65395

RH36260 (e-PCR)
- UniSTS:34442

ITPR3_1317 (e-PCR)
- UniSTS:277395

ITPR3_v399 (e-PCR)
- UniSTS:277395

G43195 (e-PCR)
- UniSTS:94894

RH46603 (e-PCR)
- UniSTS:51379

RH119684 (e-PCR)
- UniSTS:133053

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	IBA Inferred from Biological aspect of Ancestor more info
enables inositol 1,3,4,5 tetrakisphosphate binding	ISS Inferred from Sequence or Structural Similarity more info
enables inositol 1,4,5 trisphosphate binding	IBA Inferred from Biological aspect of Ancestor more info
enables inositol 1,4,5 trisphosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables inositol 1,4,5-trisphosphate-gated calcium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables inositol 1,4,5-trisphosphate-gated calcium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables inositol 1,4,5-trisphosphate-gated calcium channel activity	ISS Inferred from Sequence or Structural Similarity more info
enables inositol hexakisphosphate binding	ISS Inferred from Sequence or Structural Similarity more info
enables intracellularly gated calcium channel activity	ISS Inferred from Sequence or Structural Similarity more info
enables intracellularly gated calcium channel activity	TAS Traceable Author Statement more info
enables phosphatidylinositol binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in calcium ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in calcium-mediated signaling	IEA Inferred from Electronic Annotation more info
involved_in long-term synaptic potentiation	IEA Inferred from Electronic Annotation more info
involved_in memory	IEA Inferred from Electronic Annotation more info
involved_in platelet activation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cytosolic calcium ion concentration	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein homotetramerization	IDA Inferred from Direct Assay more info	PubMed
involved_in release of sequestered calcium ion into cytosol	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to calcium ion	IDA Inferred from Direct Assay more info	PubMed
involved_in sensory perception of bitter taste	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of sweet taste	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of taste	TAS Traceable Author Statement more info
involved_in sensory perception of umami taste	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in apical part of cell	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in brush border	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in cytoplasmic side of endoplasmic reticulum membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
is_active_in endoplasmic reticulum membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in membrane	HDA more info	PubMed
located_in neuronal cell body	ISS Inferred from Sequence or Structural Similarity more info
located_in nuclear outer membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleolus	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in platelet dense tubular network membrane	TAS Traceable Author Statement more info
part_of receptor complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in sarcoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info
is_active_in secretory granule membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in transport vesicle membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: inositol 1,4,5-trisphosphate-gated calcium channel ITPR3

Names: IP3 receptor; inositol 1,4,5-triphosphate receptor, type 3; insP3R3; type 3 InsP3 receptor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_027729.2 RefSeqGene

Range

5002..80242

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_002224.4 → NP_002215.2 inositol 1,4,5-trisphosphate-gated calcium channel ITPR3

See identical proteins and their annotated locations for NP_002215.2

Status: REVIEWED

Source sequence(s)

AL139044

Consensus CDS

CCDS4783.1

UniProtKB/Swiss-Prot

Q14573, Q14649, Q5TAQ2

UniProtKB/TrEMBL

Q59ES2

Related

ENSP00000475177.1, ENST00000605930.3

Conserved Domains (5) summary

pfam00520
Location:2265 → 2528

Ion_trans; Ion transport protein

pfam01365
Location:473 → 670

RYDR_ITPR; RIH domain

pfam02815
Location:234 → 432

MIR; MIR domain

pfam08454
Location:1865 → 1974

RIH_assoc; RyR and IP3R Homology associated

pfam08709
Location:3 → 230

Ins145_P3_rec; Inositol 1,4,5-trisphosphate/ryanodine receptor

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

33621322..33696562

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047418731.1 → XP_047274687.1 inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 isoform X2

UniProtKB/Swiss-Prot

Q14573, Q14649, Q5TAQ2

UniProtKB/TrEMBL

Q59ES2
XM_017010832.2 → XP_016866321.1 inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 isoform X3
XM_047418732.1 → XP_047274688.1 inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 isoform X1

UniProtKB/TrEMBL

Q59ES2
XM_047418734.1 → XP_047274690.1 inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 isoform X1

UniProtKB/TrEMBL

Q59ES2
XM_047418733.1 → XP_047274689.1 inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 isoform X1

UniProtKB/TrEMBL

Q59ES2
XM_011514577.4 → XP_011512879.1 inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 isoform X1

UniProtKB/TrEMBL

Q59ES2

Conserved Domains (7) summary

smart00472
Location:171 → 227

MIR; Domain in ryanodine and inositol trisphosphate receptors and protein O-mannosyltransferases

pfam00520
Location:2213 → 2467

Ion_trans; Ion transport protein

pfam01365
Location:414 → 604

RYDR_ITPR; RIH domain

pfam02815
Location:173 → 371

MIR; MIR domain

pfam08454
Location:1808 → 1913

RIH_assoc; RyR and IP3R Homology associated

pfam12730
Location:2140 → 2271

ABC2_membrane_4; ABC-2 family transporter protein

cl19745
Location:1 → 165

Ins145_P3_rec; Inositol 1,4,5-trisphosphate/ryanodine receptor

Alternate T2T-CHM13v2.0

Genomic

NC_060930.1 Alternate T2T-CHM13v2.0

Range

33442464..33517747

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054355351.1 → XP_054211326.1 inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 isoform X4

UniProtKB/TrEMBL

Q59ES2
XM_054355355.1 → XP_054211330.1 inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 isoform X5
XM_054355352.1 → XP_054211327.1 inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 isoform X1

UniProtKB/TrEMBL

Q59ES2
XM_054355353.1 → XP_054211328.1 inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 isoform X1

UniProtKB/TrEMBL

Q59ES2
XM_054355354.1 → XP_054211329.1 inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 isoform X1

UniProtKB/TrEMBL

Q59ES2