CALR

protein-coding

calreticulin, the group of MicroRNA protein coding host genes

Gene summary

Calreticulin is a highly conserved chaperone protein which resides primarily in the endoplasmic reticulum, and is involved in a variety of cellular processes, among them, cell adhesion. Additionally, it functions in protein folding quality control and calcium homeostasis. Calreticulin is also found in the nucleus, suggesting that it may have a role in transcription regulation. Systemic lupus erythematosus is associated with increased autoantibody titers against calreticulin. Recurrent mutations in calreticulin have been linked to various neoplasms, including the myeloproliferative type.[provided by RefSeq, May 2020]

MANE transcript

NM_004343.4

Inheritance

—

ClinVar variants

P:7U:55B:11

Top phenotype

Myeloproliferative neoplasm

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr19:12,938,578-12,944,489

External References & Databases

Ensembl (ENSG00000179218)

Transcript & Mutation Effects

hg38 • Region Span ~5.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CALR variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 36

not providedTotal: 22

Myeloproliferative neoplasmTotal: 8

CALR-related disorderTotal: 7

Primary myelofibrosisTotal: 3

Essential thrombocythemiaTotal: 3

Thrombocythemia 1Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004343.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	4 clinvar	2 clinvar	7
missense			44 clinvar	2 clinvar	3 clinvar	49
nonsense			1 clinvar			1
start loss						0
frameshift	1 clinvar	6 clinvar	2 clinvar			9
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	1	6	55	6	5	73

Highest pathogenic variant AF is 0.000029149167

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004343.4	RefSeq	NP_004334.1	9	MANE Select
ENST00000316448.10	Ensembl	ENSP00000320866.4	9	MANE Select
ENST00000586760.2	Ensembl	ENSP00000465918.2	10	Standard
ENST00000586760.3	Ensembl	ENSP00000465918.2	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

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

Molecular Function

complement component C1q binding
DNA binding
RNA binding
mRNA binding
integrin binding

Cellular Component

acrosomal vesicle
extracellular region
extracellular space
nucleus
nuclear envelope

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000316448
Coding exons: 9
Length: 5912
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125748
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.291	213	225	0.946	0.0000127	2816
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000057	0.000054	rare
Finnish	0.000095	0.000092	rare
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.869

Intolerance Scores

LoFtool: 0.0524
RVIS EVS: -0.62
RVIS percentile EVS: 17.16

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.997

Gene Damage Prediction

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