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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
ATP2B1
ATPase plasma membrane Ca2+ transporting 1
Chromosome 12 Β· 12q21.33
NCBI Gene: 490Ensembl: ENSG00000070961.18HGNC: HGNC:814UniProt: P20020
214PubMed Papers
21Diseases
0Drugs
41Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTransporter
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
membraneATP hydrolysis activityregulation of cytosolic calcium ion concentrationnegative regulation of cytosolic calcium ion concentrationintellectual developmental disorder, autosomal dominant 66Neurodevelopmental disorderhypertensioncoronary artery disease
✦AI Summary

ATP2B1 encodes a plasma membrane calcium-ATPase that catalyzes ATP hydrolysis to export calcium from the cytoplasm, maintaining intracellular calcium homeostasis 1. The protein functions as a calmodulin-dependent calcium pump critical for regulating intracellular free Ca2+ levels 1. Mechanism: ATP2B1 operates through calcium/calmodulin signaling pathways. In vascular smooth muscle cells, it regulates blood pressure by controlling intracellular calcium concentration and nitric oxide production 2. The gene also modulates endothelial barrier function and monocyte inflammatory responses 3. Disease relevance: De novo ATP2B1 variants cause neurodevelopmental disorder characterized by global developmental delay, autism, and seizures; functional studies show these variants significantly impair calcium export capacity and cause protein mislocalization 1. Common polymorphisms (rs2681472, rs17249754) are strongly associated with hypertension susceptibility and blood pressure elevation across multiple populations 4. ATP2B1 genetic variants also correlate with eclampsia risk, cerebral infarction, and skeletal fluorosis 567. Notably, ATP2B1 knockout showed no effect on doxorubicin-induced cardiotoxicity in functional studies 8. Clinical significance: ATP2B1 represents a validated hypertension-susceptibility gene with strong ethnicity-dependent associations, making it relevant for personalized risk assessment and potential therapeutic targeting of calcium-handling pathways in cardiovascular and neurological disorders.

Sources cited
1
De novo ATP2B1 variants cause neurodevelopmental delay through impaired calcium export; all missense variants showed decreased Ca2+ export capacity and incorrect protein localization
PMID: 35358416
2
ATP2B1 is a hypertension-susceptibility gene confirmed by GWAS; vascular smooth muscle ATP2B1 affects blood pressure regulation through calcium homeostasis
PMID: 23324996
3
ATP2B1 polymorphisms rs17249754 and rs2681472 are associated with hypertension susceptibility and elevated systolic/diastolic blood pressure
PMID: 33847678
4
ATP2B1 is upregulated in monocytes of ARDS patients and functions as a calcium pump implicated in endothelial barrier disruption
PMID: 32554932
5
ATP2B1 gene polymorphisms rs71454161, rs73196661, and rs73196675 are associated with eclampsia occurrence and progression
PMID: 35253182
6
ATP2B1 promoter polymorphisms rs19203 and rs13412 are correlated with cerebral infarction onset and vascular endothelial growth factor expression
PMID: 31173308
7
ATP2B1 polymorphisms rs17249754 and rs7136259 are associated with skeletal fluorosis risk
PMID: 37211801
8
ATP2B1 knockout had no significant effect on doxorubicin-induced cardiotoxicity in hiPSC-cardiomyocytes
PMID: 38510289
Disease Associationsβ“˜21
intellectual developmental disorder, autosomal dominant 66Open Targets
0.78Strong
Neurodevelopmental disorderOpen Targets
0.56Moderate
hypertensionOpen Targets
0.53Moderate
coronary artery diseaseOpen Targets
0.50Moderate
myocardial infarctionOpen Targets
0.49Moderate
essential hypertensionOpen Targets
0.48Moderate
prostate carcinomaOpen Targets
0.46Moderate
Abnormality of the skeletal systemOpen Targets
0.46Moderate
hair colorOpen Targets
0.45Moderate
atrial fibrillationOpen Targets
0.44Moderate
alcohol drinkingOpen Targets
0.44Moderate
major depressive disorderOpen Targets
0.43Moderate
genetic disorderOpen Targets
0.41Moderate
Increased blood pressureOpen Targets
0.41Moderate
cardiovascular diseaseOpen Targets
0.41Moderate
brain aneurysmOpen Targets
0.40Moderate
hypertension, pregnancy-inducedOpen Targets
0.40Moderate
coronary atherosclerosisOpen Targets
0.38Weak
heart diseaseOpen Targets
0.38Weak
complex neurodevelopmental disorderOpen Targets
0.37Weak
Intellectual developmental disorder, autosomal dominant 66UniProt
Pathogenic Variants41
NM_001366521.1(ATP2B1):c.1370_1373del (p.Val457fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 457
NM_001366521.1(ATP2B1):c.1789C>T (p.Arg597Ter)Pathogenic
Neurodevelopmental disorder|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 597
NM_001366521.1(ATP2B1):c.2750del (p.Tyr917fs)Likely pathogenic
Intellectual developmental disorder, autosomal dominant 66
β˜…β˜†β˜†β˜†2026β†’ Residue 917
NM_001366521.1(ATP2B1):c.2331del (p.Gly779fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 779
NM_001366521.1(ATP2B1):c.2533G>T (p.Gly845Ter)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 845
NM_001366521.1(ATP2B1):c.333_337del (p.Leu111fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 111
NM_001366521.1(ATP2B1):c.559C>T (p.Arg187Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 187
NM_001366521.1(ATP2B1):c.1339_1342del (p.Val447fs)Pathogenic
Intellectual developmental disorder, autosomal dominant 66
β˜…β˜†β˜†β˜†2025β†’ Residue 447
NM_001366521.1(ATP2B1):c.661+2dupLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_001366521.1(ATP2B1):c.2855del (p.Lys952fs)Likely pathogenic
Intellectual developmental disorder, autosomal dominant 66
β˜…β˜†β˜†β˜†2025β†’ Residue 952
NM_001366521.1(ATP2B1):c.2230C>T (p.Arg744Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 744
NM_001366521.1(ATP2B1):c.1311del (p.Ala438fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 438
NM_001366521.1(ATP2B1):c.937C>T (p.Gln313Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 313
NM_001366521.1(ATP2B1):c.2443-2A>GPathogenic
Intellectual developmental disorder, autosomal dominant 66
β˜…β˜†β˜†β˜†2024
NM_001366521.1(ATP2B1):c.1925C>A (p.Ser642Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 642
NM_001366521.1(ATP2B1):c.1829+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_001366521.1(ATP2B1):c.2954del (p.Phe985fs)Pathogenic
Intellectual developmental disorder, autosomal dominant 66
β˜…β˜†β˜†β˜†2024β†’ Residue 985
NM_001366521.1(ATP2B1):c.3215C>T (p.Ala1072Val)Likely pathogenic
Intellectual developmental disorder, autosomal dominant 66
β˜…β˜†β˜†β˜†2024β†’ Residue 1072
NM_001366521.1(ATP2B1):c.458G>A (p.Trp153Ter)Likely pathogenic
Neurodevelopmental disorder|Intellectual developmental disorder, autosomal dominant 66
β˜…β˜†β˜†β˜†2024β†’ Residue 153
NM_001366521.1(ATP2B1):c.139C>T (p.Arg47Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 47
View on ClinVar β†—
Related Genes
CALML4Protein interaction100%CALML5Protein interaction100%CALML3Protein interaction100%CALML6Protein interaction100%PRKACGProtein interaction99%PRKACBProtein interaction99%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
90%
Lung
15%
Heart
11%
Ovary
11%
Liver
11%
Gene Interaction Network
Click a node to explore
ATP2B1CALML4CALML5CALML3CALML6PRKACGPRKACB
PROTEIN STRUCTURE
Preparing viewer…
PDB6A69 Β· 4.11 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.17Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.11 [0.07–0.17]
RankingsWhere ATP2B1 stands among ~20K protein-coding genes
  • #1,935of 20,598
    Most Researched214 Β· top 10%
  • #1,507of 5,498
    Most Pathogenic Variants41
  • #303of 17,882
    Most Constrained (LOEUF)0.17 Β· top 5%
Genes detectedATP2B1
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
De novo variants in ATP2B1 lead to neurodevelopmental delay.
PMID: 35358416
Am J Hum Genet Β· 2022
1.00
2
Single cell RNA sequencing identifies an early monocyte gene signature in acute respiratory distress syndrome.
PMID: 32554932
JCI Insight Β· 2020
0.90
3
ATP2B1 gene rs71454161, rs73196661 and rs73196675 polymorphisms in eclampsia.
PMID: 35253182
Eur Rev Med Pharmacol Sci Β· 2022
0.80
4
ATP2B1 gene polymorphisms rs2681472 and rs17249754 are associated with susceptibility to hypertension and blood pressure levels: A systematic review and meta-analysis.
PMID: 33847678
Medicine (Baltimore) Β· 2021
0.70
5
Functional Validation of Doxorubicin-Induced Cardiotoxicity-Related Genes.
PMID: 38510289
JACC CardioOncol Β· 2024
0.60