CALR3 Gene: Calreticulin 3 – Function, Disease Associations, and Expression
A comprehensive biomedical overview of CALR3, including genomic context, expression, mutations, and clinical significance.
Gene Information Card
| Symbol | CALR3 |
|---|---|
| Full Name | calreticulin 3 |
| Gene Type | protein coding |
| Chromosomal Location | 19p13.11 |
| NCBI Gene ID | 126731 ncbi.nlm.nih.gov/gene/126731 |
| Ensembl ID | ENSG00000108405 |
| UniProt ID | Q96L12 |
| OMIM ID | 611414 |
| HGNC ID | 20409 |
| Aliases | cC1qR, CRT2 |
Description
CALR3 (calreticulin 3) is a protein-coding gene located on chromosome 19p13.11. It encodes a calreticulin-like protein that is predominantly expressed in the testis and is involved in spermatogenesis, particularly in sperm capacitation and acrosome reaction. CALR3 belongs to the calreticulin family of calcium-binding chaperones, though its function is more specialized in male reproduction. Mutations in CALR3 have been associated with male infertility due to sperm dysfunction.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Male infertility | Mutations in CALR3 impair sperm calcium homeostasis and acrosome reaction, leading to fertilization failure. | ClinVar, PubMed (e.g., PMID: 28130356) |
| Spermatogenic failure | Altered CALR3 expression disrupts spermatogenesis, resulting in reduced sperm count or quality. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Fallopian tube | 3.1 | Low |
| Kidney | 2.0 | Low |
| Liver | 1.5 | Low |
| Brain | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 0.5 | Low expression |
| K562 | 0.3 | Very low |
| MCF7 | 0.2 | Very low |
| HEK293 | 0.4 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.109C>T (p.Arg37Cys) | Missense | Rare (MAF <0.01) | Impairs protein folding and calcium binding, leading to sperm dysfunction. |
| c.547G>A (p.Gly183Arg) | Missense | Rare | Disrupts chaperone activity, affecting acrosome reaction. |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of translation initiation, likely loss-of-function. |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce CALR3 protein levels or disrupt its calcium-binding/chaperone function, leading to impaired sperm function.
Gain of Function (GOF)
No evidence of gain-of-function mutations; CALR3 is not known to be oncogenic.
Dominant Negative (DN)
Potential dominant-negative effects if mutant CALR3 interferes with wild-type function in sperm, but not well documented.
View complete mutation data：
Gene Ontology (GO)
| • calcium ion binding | • chaperone binding |
| • protein folding | • sperm capacitation |
| • acrosome reaction | • response to endoplasmic reticulum stress |
Pathways
• Calcium signaling pathway
• Protein processing in endoplasmic reticulum
• Spermatogenesis
Protein Summary
The CALR3 protein is a 383-amino-acid calreticulin family member with a signal peptide, an N-terminal domain, a proline-rich domain, and a C-terminal domain containing an ER retention signal (KDEL). It localizes to the endoplasmic reticulum and is involved in calcium storage and chaperone activity. In sperm, CALR3 is crucial for the acrosome reaction and sperm-egg fusion. It interacts with other proteins such as PDIA3 (ERp57) to regulate calcium flux during capacitation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CALR3 Knockout HEK293 Cell Line | EDJ-KQ8842 | Human | 125972 | Details Get a Quote |
| CALR3 Knockout HeLa Cell Line | EDJ-KQ58159 | Human | 125972 | Details Get a Quote |
| CALR3 Knockout A-549 Cell Line | EDJ-KQ66644 | Human | 125972 | Details Get a Quote |
| CALR3 Knockout HCT 116 Cell Line | EDJ-KQ75064 | Human | 125972 | Details Get a Quote |
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