CALR3

calreticulin 3

Basic information

Region (hg38): 19:16479061-16496167

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 (286 variants)
not_specified (54 variants)
not_provided (27 variants)
CALR3-related_disorder (8 variants)
Cardiovascular_phenotype (7 variants)
Hypertrophic_cardiomyopathy (6 variants)
Cardiomyopathy (4 variants)
Primary_dilated_cardiomyopathy (2 variants)
Primary_familial_hypertrophic_cardiomyopathy (1 variants)
Restrictive_cardiomyopathy (1 variants)
Arrhythmogenic_right_ventricular_cardiomyopathy (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. These statistics are base on transcript: NM_000145046.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	60 clinvar	6 clinvar	68
missense			155 clinvar	9 clinvar	2 clinvar	166
nonsense			5 clinvar			5
start loss			3			3
frameshift		1 clinvar	10 clinvar			11
splice donor/acceptor (+/-2bp)			6 clinvar	1 clinvar		7
Total	0	1	181	70	8

Highest pathogenic variant AF is 0.00012578

Loading clinvar variants...

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
ghis

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