CALR3

calreticulin 3

Basic information

Region (hg38): 19:16479060-16496167

Links

ENSG00000269058 ∙ NCBI:125972 ∙ OMIM:611414 ∙ HGNC:20407 ∙ Uniprot:Q96L12 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertrophic cardiomyopathy (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, familial hypertrophic, 19	AD	Cardiovascular	Surveillance (eg, including echocardiography) for manifestations can allow early diagnosis, preventive measures relating to disease sequelae, and prompt treatment, which may reduce morbidity and mortality	Cardiovascular	16199542; 17655857

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CALR3 gene.

• Hypertrophic cardiomyopathy 19 (217 variants)
• not provided (52 variants)
• not specified (20 variants)
• Cardiovascular phenotype (10 variants)
• Inborn genetic diseases (8 variants)
• Hypertrophic cardiomyopathy (4 variants)
• Cardiomyopathy (2 variants)
• Primary dilated cardiomyopathy (2 variants)
• Cardiomyopathy;Restrictive cardiomyopathy (1 variants)
• Arrhythmogenic right ventricular cardiomyopathy (1 variants)
• Hypertrophic cardiomyopathy;Cardiomyopathy (1 variants)
• CALR3-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CALR3 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			2	49	8	59
missense			108	5	2	115
nonsense			4			4
start loss			2			2
frameshift			6			6
inframe indel						0
splice donor/acceptor (+/-2bp)			6	1		7
splice region			4	4	3	11
non coding				20	30	50
Total	0	0	128	75	40

Variants in CALR3

This is a list of pathogenic ClinVar variants found in the CALR3 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-16479134-A-C		Hypertrophic cardiomyopathy 19	Likely benign (Jun 21, 2020)
19-16479139-C-T		Hypertrophic cardiomyopathy 19 • CALR3-related disorder	Uncertain significance (Nov 27, 2023)
19-16479152-A-T		Hypertrophic cardiomyopathy 19	Uncertain significance (Aug 04, 2023)
19-16479153-AATTG-A		Hypertrophic cardiomyopathy 19	Uncertain significance (Jan 17, 2023)
19-16479155-T-C		Hypertrophic cardiomyopathy 19	Uncertain significance (Dec 28, 2021)
19-16479157-G-C		Hypertrophic cardiomyopathy 19	Uncertain significance (Apr 26, 2023)
19-16479157-G-T		Hypertrophic cardiomyopathy 19	Uncertain significance (Oct 23, 2023)
19-16479166-A-C		Hypertrophic cardiomyopathy 19	Uncertain significance (May 09, 2021)
19-16479172-C-A		Hypertrophic cardiomyopathy 19	Uncertain significance (Nov 21, 2022)
19-16479172-C-G		Hypertrophic cardiomyopathy 19 • not specified	Conflicting classifications of pathogenicity (Dec 21, 2023)
19-16479172-C-T		Hypertrophic cardiomyopathy 19	Uncertain significance (Aug 20, 2023)
19-16479173-G-A		Hypertrophic cardiomyopathy 19	Likely benign (Jan 22, 2022)
19-16479176-C-T		Hypertrophic cardiomyopathy 19	Likely benign (Dec 27, 2023)
19-16479182-A-T		Hypertrophic cardiomyopathy 19	Likely benign (Feb 15, 2017)
19-16479191-C-G		Hypertrophic cardiomyopathy 19	Likely benign (Jan 18, 2024)
19-16479191-C-T		Hypertrophic cardiomyopathy 19	Likely benign (Jul 10, 2023)
19-16479192-G-A		Hypertrophic cardiomyopathy 19	Uncertain significance (Jul 07, 2023)
19-16479197-C-A		Hypertrophic cardiomyopathy 19	Likely benign (Mar 06, 2020)
19-16479199-G-A		Hypertrophic cardiomyopathy 19	Benign (Jan 22, 2024)
19-16479206-C-T		Hypertrophic cardiomyopathy 19	Likely benign (Aug 01, 2021)
19-16479216-TCG-T			Uncertain significance (-)
19-16479217-C-T		Hypertrophic cardiomyopathy 19 • not specified	Uncertain significance (Oct 28, 2023)
19-16479218-G-A		Hypertrophic cardiomyopathy 19	Likely benign (Aug 14, 2023)
19-16479219-C-A		Hypertrophic cardiomyopathy 19 • Cardiovascular phenotype • Primary dilated cardiomyopathy • not specified	Benign (Jan 31, 2024)
19-16479219-C-T		Hypertrophic cardiomyopathy 19	Uncertain significance (Aug 23, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CALR3	protein_coding	protein_coding	ENST00000269881	9	17136

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.98e-10	0.435	125683	0	65	125748	0.000258

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.353	195	209	0.931	0.0000117	2561
Missense in Polyphen		68	80.621	0.84345		1028
Synonymous	-0.215	87	84.5	1.03	0.00000581	650
Loss of Function	1.05	17	22.4	0.760	0.00000117	246

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000565	0.000504
Ashkenazi Jewish	0.00	0.00
East Asian	0.000113	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000354	0.000352
Middle Eastern	0.000113	0.000109
South Asian	0.000295	0.000294
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: During spermatogenesis, may act as a lectin-independent chaperone for specific client proteins such as ADAM3. Required for sperm fertility (By similarity). CALR3 capacity for calcium- binding may be absent or much lower than that of CALR. {ECO:0000250, ECO:0000269|PubMed:21590275}.
• Disease: DISEASE: Cardiomyopathy, familial hypertrophic 19 (CMH19) [MIM:613875]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:17655857}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• loftool: 0.918
• rvis_EVS: 0.15
• rvis_percentile_EVS: 64.74

Haploinsufficiency Scores

• pHI: 0.0992
• hipred: N
• hipred_score: 0.197

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.883

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Calr3
• Phenotype: reproductive system phenotype

Zebrafish Information Network

• Gene name: calr3a
• Affected structure: neuromast
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: protein folding;spermatogenesis;biological_process;cell differentiation
• Cellular component: nuclear envelope;endoplasmic reticulum lumen
• Molecular function: calcium ion binding;carbohydrate binding;protein folding chaperone;unfolded protein binding