CALR

calreticulin, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 19:12938578-12944489

Links

ENSG00000179218 ∙ NCBI:811 ∙ OMIM:109091 ∙ HGNC:1455 ∙ Uniprot:P27797 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• Thrombocythemia 1 (2 variants)
• Essential thrombocythemia (1 variants)
• Primary myelofibrosis (1 variants)
• Primary myelofibrosis;Thrombocythemia 1 (1 variants)
• Acute myeloid leukemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CALR 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				3	2	5
missense			15	1	3	19
nonsense						0
start loss						0
frameshift	2		1			3
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding				2	8	10
Total	2	0	17	6	13

Highest pathogenic variant AF is 0.0000197

Variants in CALR

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

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

Position	Type	Phenotype	Significance	ClinVar
19-12938601-C-T			Likely benign (Nov 10, 2018)
19-12938659-T-C			Benign (May 10, 2021)
19-12938676-C-T			Benign (May 05, 2021)
19-12938696-C-T		not specified	Uncertain significance (Mar 29, 2024)
19-12938729-C-G		not specified	Uncertain significance (May 18, 2023)
19-12938729-C-T		not specified	Uncertain significance (May 26, 2023)
19-12938767-G-C		not specified	Uncertain significance (Jul 19, 2022)
19-12939143-C-T		not specified	Uncertain significance (Aug 30, 2022)
19-12939156-C-G		not specified	Uncertain significance (Oct 03, 2023)
19-12939190-G-C		not specified	Uncertain significance (Jul 09, 2021)
19-12939212-A-G			Benign (Aug 20, 2018)
19-12939276-C-G			Benign (May 10, 2021)
19-12939387-A-G			Benign (May 10, 2021)
19-12939465-G-T			Likely benign (Jul 31, 2018)
19-12939496-G-C			Uncertain significance (Jun 01, 2024)
19-12939511-G-A		not specified	Uncertain significance (Nov 30, 2022)
19-12939563-T-C			Uncertain significance (Aug 01, 2024)
19-12939613-G-C		not specified	Uncertain significance (Sep 10, 2024)
19-12939896-C-G			Likely benign (Feb 19, 2021)
19-12940257-A-T		CALR-related disorder	Likely benign (Jul 02, 2018)
19-12940286-A-G		not specified	Uncertain significance (Sep 14, 2021)
19-12940316-G-C		CALR-related disorder	Likely benign (Feb 01, 2022)
19-12940336-T-G		not specified	Uncertain significance (Sep 14, 2022)
19-12940356-C-T			Benign (Aug 21, 2018)
19-12940397-C-T		not specified	Uncertain significance (Aug 02, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CALR	protein_coding	protein_coding	ENST00000316448	9	5912

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.891	0.109	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.291	213	225	0.946	0.0000127	2816
Missense in Polyphen		54	80.4	0.67164		985
Synonymous	-2.55	125	93.6	1.34	0.00000643	701
Loss of Function	3.57	3	20.4	0.147	9.14e-7	253

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000148	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000571	0.0000544
Finnish	0.0000949	0.0000924
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.0000571	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently with almost all of the monoglucosylated glycoproteins that are synthesized in the ER. Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export. Involved in maternal gene expression regulation. May participate in oocyte maturation via the regulation of calcium homeostasis (By similarity). {ECO:0000250, ECO:0000269|PubMed:11149926, ECO:0000269|PubMed:7876246}.
• Pathway: Antigen processing and presentation - Homo sapiens (human);Phagosome - Homo sapiens (human);Protein processing in endoplasmic reticulum - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Androgen receptor signaling pathway;ATF6 (ATF6-alpha) activates chaperone genes;Human Complement System;Photodynamic therapy-induced unfolded protein response;Calcium Regulation in the Cardiac Cell;Disease;Vesicle-mediated transport;nfat and hypertrophy of the heart ;Calnexin/calreticulin cycle;Post-translational protein modification;Assembly of Viral Components at the Budding Site;Metabolism of proteins;Virus Assembly and Release;Influenza Life Cycle;Influenza Infection;Infectious disease;Immune System;Adaptive Immune System;Antigen processing-Cross presentation;Class I MHC mediated antigen processing & presentation;Asparagine N-linked glycosylation;ER-Phagosome pathway;TSH;N-glycan trimming in the ER and Calnexin/Calreticulin cycle;Binding and Uptake of Ligands by Scavenger Receptors;Scavenging by Class A Receptors;Antigen Presentation: Folding, assembly and peptide loading of class I MHC;Scavenging by Class F Receptors (Consensus)

Recessive Scores

• pRec: 0.869

Intolerance Scores

• loftool: 0.0524
• rvis_EVS: -0.62
• rvis_percentile_EVS: 17.16

Haploinsufficiency Scores

• pHI: 0.898
• hipred: Y
• hipred_score: 0.831
• ghis: 0.594

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.997

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Calr
• Phenotype: growth/size/body region phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; embryo 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;antigen processing and presentation of peptide antigen via MHC class I;antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent;peptide antigen assembly with MHC class I protein complex;regulation of transcription, DNA-templated;protein folding;protein export from nucleus;cellular calcium ion homeostasis;receptor-mediated endocytosis;spermatogenesis;positive regulation of cell population proliferation;positive regulation of endothelial cell migration;positive regulation of gene expression;negative regulation of translation;protein maturation by protein folding;cortical actin cytoskeleton organization;response to estradiol;negative regulation of intracellular steroid hormone receptor signaling pathway;response to testosterone;protein localization to nucleus;protein folding in endoplasmic reticulum;ATF6-mediated unfolded protein response;regulation of meiotic nuclear division;response to drug;glucocorticoid receptor signaling pathway;regulation of apoptotic process;negative regulation of neuron differentiation;positive regulation of cell cycle;negative regulation of transcription, DNA-templated;negative regulation of retinoic acid receptor signaling pathway;positive regulation of phagocytosis;protein stabilization;sequestering of calcium ion;cardiac muscle cell differentiation;chaperone-mediated protein folding;negative regulation of cell cycle arrest;cellular response to lithium ion;cellular senescence;positive regulation of substrate adhesion-dependent cell spreading;negative regulation of trophoblast cell migration;positive regulation of NIK/NF-kappaB signaling;vesicle fusion with endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane;positive regulation of dendritic cell chemotaxis
• Cellular component: acrosomal vesicle;extracellular region;extracellular space;nucleus;nuclear envelope;cytoplasm;endoplasmic reticulum;endoplasmic reticulum lumen;smooth endoplasmic reticulum;Golgi apparatus;cytosol;polysome;focal adhesion;external side of plasma membrane;cell surface;membrane;phagocytic vesicle membrane;sarcoplasmic reticulum lumen;endoplasmic reticulum-Golgi intermediate compartment membrane;MHC class I peptide loading complex;endoplasmic reticulum quality control compartment;perinuclear region of cytoplasm;collagen-containing extracellular matrix;extracellular exosome;integral component of lumenal side of endoplasmic reticulum membrane;endocytic vesicle lumen
• Molecular function: complement component C1q binding;DNA binding;RNA binding;mRNA binding;integrin binding;iron ion binding;calcium ion binding;protein binding;zinc ion binding;carbohydrate binding;ubiquitin protein ligase binding;peptide binding;hormone binding;protein folding chaperone;androgen receptor binding;unfolded protein binding;chaperone binding