ATP2A3
protein-codingATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3, the group of ATPases Ca2+ transporting
Gene summary
This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in calcium sequestration associated with muscular excitation and contraction. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~40.6 kbGenCC 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 ATP2A3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005173.4. 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 | 3 | 24 | 10 | 37 | ||
| missense | 134 | 8 | 3 | 145 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 139 | 32 | 13 | 184 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005164.2 | 21 | MANE Select | |
| Ensembl | ENSP00000380234.3 | 21 | MANE Select | |
| RefSeq | NP_777613.1 | 23 | Standard | |
| RefSeq | NP_777614.1 | 23 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Alzheimer,s disease - Homo sapiens (human)
- Calcium signaling pathway - Homo sapiens (human)
- Pancreatic secretion - Homo sapiens (human)
- cGMP-PKG signaling pathway - Homo sapiens (human)
- Celecoxib Pathway, Pharmacodynamics
Biological Process
- calcium ion transport
- cellular calcium ion homeostasis
- ion transmembrane transport
- calcium ion transmembrane transport
- ATP hydrolysis coupled cation transmembrane transport
Molecular Function
- calcium-transporting ATPase activity
- ATP binding
- proton-exporting ATPase activity, phosphorylative mechanism
- metal ion binding
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- integral component of membrane
- sarcoplasmic reticulum
- platelet dense tubular network membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000359983
- Coding exons
- 23
- Length
- 40568
- Individuals with no LoFs
- 125703
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 45
- Defined
- 125748
- p
- 0.000179
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.83 | 537 | 671 | 0.801 | 0.0000498 | 6711 |
| Missense (PolyPhen) | 230 | 351.92 | 0.65356 | 3550 | ||
| Synonymous | -2.53 | 352 | 297 | 1.19 | 0.0000244 | 2219 |
| Loss of Function | 3.51 | 23 | 49.7 | 0.463 | 0.00000279 | 518 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00026 | 0.00025 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00050 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. Transports calcium ions from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction. {ECO:0000269|PubMed:11956212, ECO:0000269|PubMed:15028735}.;
Recessive Scores
- pRec
- 0.198
Intolerance Scores
- LoFtool
- 0.00675
- RVIS EVS
- -1.47
- RVIS percentile EVS
- 3.74
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.615
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |