ITPR3

inositol 1,4,5-trisphosphate receptor type 3, the group of Protein phosphatase 1 regulatory subunits|Inositol 1,4,5-triphosphate receptors

Basic information

Region (hg38): 6:33620364-33696574

Links

ENSG00000096433 ∙ NCBI:3710 ∙ OMIM:147267 ∙ HGNC:6182 ∙ Uniprot:Q14573 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Charcot-Marie-Tooth disease, demyelinating, type 1J (Limited), mode of inheritance: AD
• Charcot-Marie-Tooth disease, demyelinating, type 1J (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Charcot-Marie-Tooth disease, demyelinating, type 1J	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	24627108; 27549087; 32949214

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ITPR3 gene.

• not provided (207 variants)
• Inborn genetic diseases (102 variants)
• Charcot-Marie-Tooth disease, demyelinating, type 1J (4 variants)
• ITPR3-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ITPR3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				25	27	52
missense		1	118	8	7	134
nonsense			2			2
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			2	8	8	18
non coding				2	98	100
Total	0	1	122	35	132

Variants in ITPR3

This is a list of pathogenic ClinVar variants found in the ITPR3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-33621208-C-A			Benign (May 16, 2021)
6-33621255-G-C			Benign (May 12, 2021)
6-33621555-C-T			Benign (May 12, 2021)
6-33621614-G-A		not specified	Uncertain significance (Feb 05, 2024)
6-33621627-C-T		not specified	Uncertain significance (Jul 26, 2022)
6-33640439-G-T			Benign (May 12, 2021)
6-33640524-G-C		not specified	Uncertain significance (Jul 26, 2021)
6-33640553-T-C		ITPR3-related disorder	Likely benign (Sep 11, 2019)
6-33640602-T-C			Benign (May 12, 2021)
6-33655732-T-C			Benign (May 12, 2021)
6-33655771-C-G		not specified	Uncertain significance (Feb 23, 2023)
6-33655780-G-A			Uncertain significance (Mar 09, 2023)
6-33655803-G-A		ITPR3-related disorder	Likely benign (May 02, 2019)
6-33655807-C-A		not specified	Uncertain significance (Dec 06, 2021)
6-33655857-C-T			Likely benign (Apr 16, 2018)
6-33655890-A-ATG			Benign (Apr 10, 2022)
6-33656045-G-A			Benign (May 23, 2021)
6-33657823-GT-G			Benign (May 12, 2021)
6-33657919-T-C			Benign (May 04, 2021)
6-33657937-G-A			Likely benign (Jul 31, 2018)
6-33657958-A-G		ITPR3-related disorder	Benign/Likely benign (Aug 01, 2022)
6-33657971-A-G		not specified	Uncertain significance (Jan 17, 2023)
6-33658734-A-G		not specified	Uncertain significance (Apr 25, 2022)
6-33658738-C-T		ITPR3-related disorder	Likely benign (Sep 26, 2019)
6-33658745-C-T			Uncertain significance (Feb 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ITPR3	protein_coding	protein_coding	ENST00000374316	58	76210

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.55e-22	1.00	125560	0	188	125748	0.000748

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.55	1144	1.67e+3	0.686	0.000111	17656
Missense in Polyphen		285	513.73	0.55476		5412
Synonymous	1.69	641	698	0.919	0.0000487	5106
Loss of Function	5.70	59	129	0.458	0.00000618	1478

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00156	0.00154
Ashkenazi Jewish	0.0000996	0.0000992
East Asian	0.000497	0.000489
Finnish	0.000378	0.000370
European (Non-Finnish)	0.000963	0.000950
Middle Eastern	0.000497	0.000489
South Asian	0.000447	0.000425
Other	0.00115	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium.
• Pathway: Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Platelet activation - Homo sapiens (human);Cortisol synthesis and secretion - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Long-term potentiation - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);Thyroid hormone synthesis - Homo sapiens (human);Long-term depression - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Gap junction - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Renin secretion - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Apoptosis - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Taste transduction - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Alzheimers Disease;Myometrial Relaxation and Contraction Pathways;MFAP5-mediated ovarian cancer cell motility and invasiveness;GPR40 Pathway;Calcium Regulation in the Cardiac Cell;Signaling by GPCR;Antigen activates B Cell Receptor (BCR) leading to generation of second messengers;Signaling by WNT;Signal Transduction;VEGFA-VEGFR2 Pathway;B cell receptor signaling;GPCR GroupI metabotropic glutamate receptor;Signaling by the B Cell Receptor (BCR);GPCR signaling-G alpha q;CLEC7A (Dectin-1) induces NFAT activation;CD4 T cell receptor signaling-ERK cascade;CLEC7A (Dectin-1) signaling;C-type lectin receptors (CLRs);Role of phospholipids in phagocytosis;Fcgamma receptor (FCGR) dependent phagocytosis;FCERI mediated Ca+2 mobilization;Fc epsilon receptor (FCERI) signaling;Innate Immune System;Immune System;Metabolism;Adaptive Immune System;Ion homeostasis;Regulation of insulin secretion;Effects of PIP2 hydrolysis;Cardiac conduction;Muscle contraction;Platelet activation, signaling and aggregation;Ca2+ pathway;Beta-catenin independent WNT signaling;Hemostasis;DAG and IP3 signaling;Signaling by VEGF;PLC beta mediated events;G-protein mediated events;Opioid Signalling;G alpha (i) signalling events;Signaling by Receptor Tyrosine Kinases;Integration of energy metabolism;Elevation of cytosolic Ca2+ levels;Platelet calcium homeostasis;VEGF;Platelet homeostasis;G alpha (q) signalling events;GPCR downstream signalling;Intracellular signaling by second messengers;CD4 T cell receptor signaling-JNK cascade;CD4 T cell receptor signaling-NFkB cascade;VEGFR2 mediated cell proliferation;CD4 T cell receptor signaling (Consensus)

Intolerance Scores

• loftool: 0.0485
• rvis_EVS: -4.09
• rvis_percentile_EVS: 0.17

Haploinsufficiency Scores

• pHI: 0.696
• hipred: Y
• hipred_score: 0.603
• ghis: 0.618

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.862

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Itpr3
• Phenotype: reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); muscle phenotype; digestive/alimentary phenotype; craniofacial phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; taste/olfaction phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: itpr3
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;positive regulation of cytosolic calcium ion concentration;memory;platelet activation;inositol phosphate-mediated signaling;regulation of insulin secretion;sensory perception of bitter taste;sensory perception of sweet taste;sensory perception of umami taste;release of sequestered calcium ion into cytosol;protein homooligomerization;protein heterooligomerization;response to calcium ion;long-term synaptic potentiation;calcium ion transport into cytosol;regulation of cardiac conduction
• Cellular component: nuclear outer membrane;nucleoplasm;nucleolus;cytoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;integral component of plasma membrane;brush border;membrane;sarcoplasmic reticulum;cytoplasmic vesicle membrane;secretory granule membrane;platelet dense tubular network membrane;neuronal cell body;myelin sheath;receptor complex;apical part of cell
• Molecular function: inositol hexakisphosphate binding;inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity;calcium ion binding;protein binding;calcium-release channel activity;phosphatidylinositol binding;inositol 1,3,4,5 tetrakisphosphate binding;inositol 1,4,5 trisphosphate binding