ITPR2

inositol 1,4,5-trisphosphate receptor type 2, the group of Inositol 1,4,5-triphosphate receptors|Cilia and flagella associated

Basic information

Region (hg38): 12:26335351-26833194

Links

ENSG00000123104 ∙ NCBI:3709 ∙ OMIM:600144 ∙ HGNC:6181 ∙ Uniprot:Q14571 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• isolated anhidrosis with normal sweat glands (Limited), mode of inheritance: AR
• isolated anhidrosis with normal sweat glands (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Anhidrosis, isolated, with normal sweat glands (Dann-Epstein-Sohar syndrome)	AR	Dermatologic	Individuals have been described as manifesting with severe heat intolerance, and awareness can allow measures to help control temperature in order to decrease potential sequelae	Dermatologic	25329695

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ITPR2 gene.

• Inborn genetic diseases (62 variants)
• not provided (27 variants)
• Isolated anhidrosis with normal sweat glands (9 variants)
• Intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ITPR2 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				8	9	17
missense			64	6	4	74
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2	2	4
non coding					3	3
Total	0	0	64	14	16

Variants in ITPR2

This is a list of pathogenic ClinVar variants found in the ITPR2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-26339416-T-A		not specified	Uncertain significance (Mar 14, 2023)
12-26340199-G-C		not specified	Uncertain significance (Jul 25, 2023)
12-26340222-G-A		not specified	Uncertain significance (Nov 09, 2021)
12-26340268-C-T		not specified	Uncertain significance (Aug 17, 2022)
12-26387528-T-C		not specified	Uncertain significance (Apr 12, 2023)
12-26387567-T-C		not specified	Uncertain significance (Dec 20, 2022)
12-26398927-T-C		not specified	Uncertain significance (Feb 15, 2023)
12-26398983-A-T		not specified	Uncertain significance (Feb 28, 2024)
12-26400166-C-T		Isolated anhidrosis with normal sweat glands	Pathogenic (Nov 01, 2014)
12-26400226-T-A		not specified	Uncertain significance (Apr 06, 2022)
12-26411344-G-C		not specified	Uncertain significance (Dec 21, 2023)
12-26411391-A-C		not specified	Uncertain significance (May 23, 2023)
12-26419155-C-T		not specified	Uncertain significance (May 05, 2023)
12-26419193-A-G			Likely benign (Apr 17, 2018)
12-26428025-A-G		not specified	Uncertain significance (Jun 06, 2022)
12-26428080-A-G		not specified	Uncertain significance (Jun 18, 2021)
12-26436298-C-T		not specified	Uncertain significance (May 27, 2022)
12-26436338-C-T		not specified	Uncertain significance (Dec 17, 2021)
12-26439157-T-C		not specified	Uncertain significance (Jan 23, 2024)
12-26439219-G-C		Isolated anhidrosis with normal sweat glands	Benign/Likely benign (Jan 20, 2022)
12-26439249-C-T		not specified	Uncertain significance (Jul 05, 2023)
12-26439302-C-T			Likely benign (Jun 01, 2022)
12-26475302-G-C		ITPR2-related disorder	Likely benign (Mar 08, 2019)
12-26475318-T-A		not specified	Uncertain significance (Apr 06, 2022)
12-26475329-A-G		ITPR2-related disorder	Likely benign (May 22, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ITPR2	protein_coding	protein_coding	ENST00000381340	57	495790

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.71e-29	1.00	124656	0	146	124802	0.000585

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.71	1030	1.42e+3	0.723	0.0000750	17914
Missense in Polyphen		244	460.39	0.52999		5940
Synonymous	-0.618	541	523	1.03	0.0000291	4943
Loss of Function	5.45	71	141	0.505	0.00000763	1755

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00111	0.00110
Ashkenazi Jewish	0.00	0.00
East Asian	0.000448	0.000445
Finnish	0.000325	0.000325
European (Non-Finnish)	0.000640	0.000627
Middle Eastern	0.000448	0.000445
South Asian	0.000885	0.000850
Other	0.000837	0.000825

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. This release is regulated by cAMP both dependently and independently of PKA (By similarity). {ECO:0000250|UniProtKB:Q9Z329}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:25329695}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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);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);Alzheimers Disease;Myometrial Relaxation and Contraction Pathways;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;Signaling by the B Cell Receptor (BCR);CLEC7A (Dectin-1) induces NFAT activation;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;BCR;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;Platelet homeostasis;G alpha (q) signalling events;GPCR downstream signalling;Intracellular signaling by second messengers;VEGFR2 mediated cell proliferation (Consensus)

Recessive Scores

• pRec: 0.206

Intolerance Scores

• loftool: 0.139
• rvis_EVS: -1.64
• rvis_percentile_EVS: 2.78

Haploinsufficiency Scores

• pHI: 0.901
• hipred: Y
• hipred_score: 0.578
• ghis: 0.576

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.726

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Itpr2
• Phenotype: homeostasis/metabolism 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; digestive/alimentary phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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)

Gene ontology

• Biological process: response to hypoxia;signal transduction;platelet activation;inositol phosphate-mediated signaling;regulation of insulin secretion;release of sequestered calcium ion into cytosol;cellular response to cAMP;cellular response to ethanol;regulation of cardiac conduction
• Cellular component: nucleus;endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;cell cortex;membrane;integral component of membrane;sarcoplasmic reticulum;cytoplasmic vesicle membrane;secretory granule membrane;platelet dense tubular network membrane;sarcoplasmic reticulum membrane;receptor complex
• Molecular function: inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity;calcium ion binding;calcium ion transmembrane transporter activity;phosphatidylinositol binding;inositol 1,4,5 trisphosphate binding;scaffold protein binding