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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ATP2C2
ATPase secretory pathway Ca2+ transporting 2
Chromosome 16 · 16q24.1
NCBI Gene: 9914Ensembl: ENSG00000064270.15HGNC: HGNC:29103UniProt: B3KR57
31PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
P-type manganese transporter activityP-type calcium transporter activityprotein bindingGolgi membranecorneal degenerationchronic obstructive pulmonary diseasepoisoningCannabis use
✦AI Summary

ATP2C2 encodes SPCA2, a P-type ATPase that transports calcium and manganese ions into the Golgi lumen, essential for protein processing and secretory pathway function 1. The pump operates through ATP-driven conformational changes, acquiring cytoplasmic ions and delivering them to the Golgi lumen 2. Beyond ATP-driven transport, ATP2C2 mediates store-independent calcium influx by interacting with the ORAI1 channel at the plasma membrane, potentially facilitating transepithelial calcium transport in mammary epithelial cells for milk secretion 3. Clinically, ATP2C2 variants are implicated in neurodevelopmental disorders. A rare missense variant associates with language impairment at higher frequency (1.8%) in affected individuals compared to controls (0.9%), with carriers showing reduced performance on reading and language measures 4. Multiple studies confirm ATP2C2's role in specific language impairment, particularly affecting phonological short-term memory through independent genetic effects 5. Beyond language, genome-wide association identified ATP2C2 variants associated with age at cannabis initiation, consistent with calcium signaling's role in substance use pathways 6. In cancer biology, ATP2C2 expression correlates with breast cancer prognosis and tumor microenvironment composition, negatively predicting survival while regulating immune cell infiltration 7. These findings establish ATP2C2 as a multifunctional calcium regulator with significant implications for neurodevelopmental and oncological disease pathways.

Sources cited
1
ATP2C2/SPCA2 supplies Golgi with Ca2+ and Mn2+ essential for protein processing and trafficking
PMID: 15677451
2
ATP-driven pump mechanism with transient phosphorylation coupling ion transport to ATP hydrolysis
PMID: 15831496
3
ATP2C2 mediates store-independent Ca2+ influx via ORAI1 interaction at basolateral membrane
PMID: 20887894
4
Rare ATP2C2 missense variant associates with language impairment (1.8% vs 0.9% controls) and reduced reading/language performance
PMID: 33864365
5
ATP2C2 variants modulate phonological short-term memory in specific language impairment through independent genetic effects
PMID: 19646677
6
ATP2C2 genome-wide association with age at cannabis initiation, consistent with calcium signaling in substance use
PMID: 30003630
7
ATP2C2 expression predicts breast cancer prognosis and correlates with tumor immune microenvironment composition
PMID: 33936088
Disease Associationsⓘ20
corneal degenerationOpen Targets
0.34Weak
chronic obstructive pulmonary diseaseOpen Targets
0.34Weak
poisoningOpen Targets
0.31Weak
Cannabis useOpen Targets
0.30Weak
cholelithiasisOpen Targets
0.27Weak
neurodegenerative diseaseOpen Targets
0.22Weak
heart diseaseOpen Targets
0.18Weak
gastrointestinal diseaseOpen Targets
0.18Weak
triple-negative breast cancerOpen Targets
0.09Suggestive
neuroendocrine neoplasmOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.04Suggestive
hemoglobin D diseaseOpen Targets
0.04Suggestive
breast cancerOpen Targets
0.04Suggestive
hemolytic anemia due to diphosphoglycerate mutase deficiencyOpen Targets
0.04Suggestive
Kimura diseaseOpen Targets
0.03Suggestive
papillary thyroid carcinomaOpen Targets
0.02Suggestive
language impairmentOpen Targets
0.02Suggestive
cancerOpen Targets
0.01Suggestive
ischemiaOpen Targets
0.01Suggestive
dyslexiaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DCDC2Protein interaction98%CMIPProtein interaction94%ORAI1Protein interaction89%F7Protein interaction82%TMEM165Shared pathway80%KIAA0319Protein interaction75%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
16%
Brain
1%
Liver
1%
Ovary
1%
Heart
0%
Gene Interaction Network
Click a node to explore
ATP2C2DCDC2CMIPORAI1F7TMEM165KIAA0319
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt O75185
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.71LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.50 [1.32–1.71]
RankingsWhere ATP2C2 stands among ~20K protein-coding genes
  • #11,667of 20,598
    Most Researched31
  • #16,160of 17,882
    Most Constrained (LOEUF)1.71
Genes detectedATP2C2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
A rare missense variant in the ATP2C2 gene is associated with language impairment and related measures.
PMID: 33864365
Hum Mol Genet · 2021
1.00
2
Genome-wide association meta-analysis of age at first cannabis use.
PMID: 30003630
Addiction · 2018
0.90
3
Store-independent Orai1-mediated Ca
PMID: 30921687
Cell Calcium · 2019
0.80
4
Genetic advances in the study of speech and language disorders.
PMID: 20955937
Neuron · 2010
0.70
5
ATP2C2 Has Potential to Define Tumor Microenvironment in Breast Cancer.
PMID: 33936088
Front Immunol · 2021
0.60