ATP2B1

Summary

ATP2B1 (ATPase plasma membrane Ca2+ transporting 1, HGNC:814) is a protein-coding gene on chromosome 12q21.33, encoding Plasma membrane calcium-transporting ATPase 1 (P20020). Catalyzes the hydrolysis of ATP coupled with the transport of calcium from the cytoplasm to the extracellular space thereby maintaining intracellular calcium homeostasis. It is a selective cancer dependency (DepMap: 13.1% of cell lines).

The protein encoded by this gene belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. These enzymes remove bivalent calcium ions from eukaryotic cells against very large concentration gradients and play a critical role in intracellular calcium homeostasis. The mammalian plasma membrane calcium ATPase isoforms are encoded by at least four separate genes and the diversity of these enzymes is further increased by alternative splicing of transcripts. The expression of different isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. This gene encodes the plasma membrane calcium ATPase isoform 1. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 490 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder, autosomal dominant 66 (Strong, GenCC)
• GWAS associations: 157
• Clinical variants (ClinVar): 279 total — 17 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 24
• Cancer dependency (DepMap): dependent in 13.1% of screened cell lines
• MANE Select transcript: NM_001366521

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:814
Approved symbol	ATP2B1
Name	ATPase plasma membrane Ca2+ transporting 1
Location	12q21.33
Locus type	gene with protein product
Status	Approved
Aliases	PMCA1
Ensembl gene	ENSG00000070961
Ensembl biotype	protein_coding
OMIM	108731
Entrez	490

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 4 retained_intron

ENST00000359142, ENST00000428670, ENST00000549585, ENST00000549727, ENST00000550716, ENST00000551009, ENST00000551310, ENST00000552275, ENST00000635033, ENST00000705786, ENST00000705822, ENST00000900650, ENST00000900651, ENST00000900652, ENST00000939928, ENST00000939929, ENST00000939930, ENST00000939931, ENST00000939932, ENST00000960958, ENST00000960959, ENST00000960960, ENST00000960961

RefSeq mRNA: 30 — MANE Select: NM_001366521 NM_001001323, NM_001366520, NM_001366521, NM_001366522, NM_001366523, NM_001366524, NM_001366525, NM_001366526, NM_001366527, NM_001366528, NM_001366529, NM_001366530, NM_001366531, NM_001366532, NM_001413046, NM_001413047, NM_001413048, NM_001413049, NM_001413050, NM_001413051, NM_001413052, NM_001413053, NM_001413054, NM_001413055, NM_001413056, NM_001413057, NM_001413058, NM_001413059, NM_001413060, NM_001682

CCDS: CCDS41817, CCDS9035, CCDS91736

Canonical transcript exons

ENST00000428670 — 21 exons

Exon	Start	End
ENSE00000431395	89634778	89634903
ENSE00000431400	89621549	89621791
ENSE00000431401	89619999	89620240
ENSE00000752974	89627678	89627716
ENSE00000752975	89630505	89630645
ENSE00000752977	89634997	89635251
ENSE00000843464	89624183	89624397
ENSE00000843465	89626454	89626615
ENSE00000909422	89599117	89599299
ENSE00000909423	89601326	89601433
ENSE00000909436	89611193	89611372
ENSE00000909438	89616802	89617039
ENSE00001143498	89642158	89642355
ENSE00001212262	89603043	89603254
ENSE00001758012	89603712	89603925
ENSE00002332582	89655679	89656107
ENSE00002370349	89708596	89708838
ENSE00002374790	89588049	89591295
ENSE00003513817	89609937	89610043
ENSE00003595977	89610421	89610508
ENSE00003686903	89604155	89604346

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 98.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 62.3566 / max 1406.6542, expressed in 1815 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132492	35.8620	1784
132500	19.8524	1744
132501	2.5295	632
132495	1.3045	497
132494	0.5882	251
132491	0.5353	229
132496	0.4897	254
132493	0.2699	143
132476	0.2060	72
206831	0.1939	70

Top tissues by expression

301 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	98.79	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.73	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.51	gold quality
occipital lobe	UBERON:0002021	97.93	gold quality
primary visual cortex	UBERON:0002436	97.92	gold quality
jejunal mucosa	UBERON:0000399	97.73	gold quality
lateral globus pallidus	UBERON:0002476	97.65	gold quality
secondary oocyte	CL:0000655	97.62	gold quality
cartilage tissue	UBERON:0002418	97.37	gold quality
superior frontal gyrus	UBERON:0002661	97.04	gold quality
orbitofrontal cortex	UBERON:0004167	97.02	gold quality
stromal cell of endometrium	CL:0002255	96.98	gold quality
CA1 field of hippocampus	UBERON:0003881	96.95	gold quality
endothelial cell	CL:0000115	96.85	gold quality
prefrontal cortex	UBERON:0000451	96.74	gold quality
parietal lobe	UBERON:0001872	96.55	gold quality
cerebellar vermis	UBERON:0004720	96.46	gold quality
middle frontal gyrus	UBERON:0002702	96.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.18	gold quality
postcentral gyrus	UBERON:0002581	96.17	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.04	gold quality
frontal cortex	UBERON:0001870	96.03	gold quality
entorhinal cortex	UBERON:0002728	95.67	gold quality
caudate nucleus	UBERON:0001873	95.66	gold quality
putamen	UBERON:0001874	95.53	gold quality
neocortex	UBERON:0001950	95.50	gold quality
cortical plate	UBERON:0005343	95.49	gold quality
cauda epididymis	UBERON:0004360	95.36	gold quality
nucleus accumbens	UBERON:0001882	95.26	gold quality
middle temporal gyrus	UBERON:0002771	95.24	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-GEOD-114530	yes	1244.14
E-MTAB-11121	yes	743.55
E-HCAD-25	yes	80.75
E-HCAD-35	yes	39.39
E-MTAB-7316	yes	38.42
E-MTAB-9467	yes	34.13
E-GEOD-137537	yes	15.43
E-MTAB-8271	yes	9.02
E-MTAB-9388	yes	8.17
E-MTAB-9801	yes	7.77
E-CURD-89	no	787.71
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, GATA3, MYB, SLC8A1, SLC8A2

miRNA regulators (miRDB)

181 targeting ATP2B1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Plasma membrane Ca2+ ATPase isoform 2b interacts preferentially with Na+/H+ exchanger regulatory factor 2 in apical plasma membranes (PMID:11786550)
• role in the intracellular Ca(2+) extrusion of syncytiotrophoblast-like structure originating from the differentiation of cultured trophoblast cells isolated from human term placenta (PMID:12784250)
• PMCA1 has a high sensitivity to degradation by calpain (PMID:12851406)
• modulation of PMCA has important effects in regulating the proliferation of human breast cancer MCF-7 cells, involving changes in cell cycle kinetics but not cell cycle arrest (PMID:15911623)
• Inactivation of the PMCA1 gene is a frequent and early event during oral carcinogenesis, and gene expression may be regulated by an epigenetic mechanism. (PMID:16328033)
• PMCA activity is influenced by membrane lipid composition and structure. The naturally high degree of lipid order in plasma membranes such as those found in human lens may serve to support PMCA activity. (PMID:16412504)
• Alterations in the region of the alternative splicing site A change the sensitivity to Ca(2+) of the human isoform 4 of the PMCA. (PMID:16488415)
• This phenomenon correlates with the greater increase in [Ca2+]c induced by higher concentrations of thrombin, which further confirms that SERCA and PMCA activities are regulated by [Ca2+]c (PMID:16669348)
• Despite similar total calcium contents, lower SERCA and PMCA activities were found in sacs associated with hydrocele compared to those associated with undescended testis suggest a difference among the levels of cytosolic calcium. (PMID:16933204)
• PMCA1 is shown to be present in the human syncytiotrophoblast homogenate. (PMID:18657858)
• PMCA is the main mechanism involved in Ca(2+) efflux in ECV 304 cells. (PMID:18929409)
• Muscarinic-induced recruitment of plasma membrane Ca2+-ATPase involves PSD-95/Dlg/Zo-1-mediated interactions. (PMID:19017653)
• These results indicate that in intact cells the Ca(2+) pump is protected from glycation-induced inactivation. (PMID:19070897)
• Data show that the calcium dependencies of intracellular Ca(2+)-ATPase (SERCA and SPCA) activity are the same in human Alzheimer disease and normal brain but that of plasma membrane Ca(2+)-ATPase (PMCA) is different. (PMID:19144698)
• Data show that in the presence of plasma membrane Ca(2+) ATPase inhibitors, locally-released Ca(2+) propagates from one cell to another, indicating that Ca(2+) was self-amplified to mediate intercellular Ca(2+) waves. (PMID:19840794)
• The transmembrane domain of the PMCA undergoes major rearrangements resulting in altered lipid accessibility upon Ca(2+) binding and activation. (PMID:19892708)
• Consistent genetic factors for ATP2B1, CSK, ARSG and CSMD1 were present, which have been shown to be associated with high blood pressure and hypertension in two Korean cohorts. (PMID:19960030)
• this study confirmed common genetic variation in ATP2B1 to be associated with blood pressure levels and risk of hypertension (PMID:20921432)
• Cloned the C-terminal domain of the human PMCA isoform 1b, and characterized its properties in solution. The expressed protein maintains its tendency to oligomerize in aqueous solutions, but it is dissociated by amphipathic molecules. (PMID:21126504)
• Immunohistochemical analysis of the distribution of TRPV6 and PMCA1 in the uterus revealed that both proteins are abundantly expressed in the cytoplasm of endometrial and glandular epithelial cells during menstrual phases. (PMID:21400627)
• Polymorphism near the ATP2B1 gene is associated with hypertension risk in East Asians. (PMID:22229515)
• The authors provide data revealing both functional and physical links between the activation of stromal interacting molecule 1 (STIM1) and PMCA-mediated Ca(2+) clearance. (PMID:22246182)
• Association of the ATP2B1 gene and susceptibility to hypertension, blood pressure traits and carotid-femoral pulse wave velocities in a Chinese population. (PMID:23079715)
• The present study confirmed the significant association of ATP2B1 rs17249754 with risk of hypertension among Chinese children. (PMID:23759979)
• The downregulation of PMCA1 and the disruption of calcium homeostasis may play important roles in UVB-induced HLE B-3 cell apoptosis. (PMID:23817774)
• analysis of how human plasma membrane Ca2+ pump PMCA h4xb is hyperactivated by mutation of Glu99 to Lys (PMID:24584935)
• Report that ATP2B1 rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women. (PMID:24642721)
• ATP2B1 rs12817819 A allele is associated with increased risk for drug resistant hypertension. (PMID:25385345)
• An increase of phosphatidylcholine/detergent molar ratio leads to a biphasic behavior of the PMCA Ca2+-ATPase activity, whose maximum depends on phosphatidylcholine characteristics. (PMID:25605721)
• rs11105378 near ATP2B1 was associated with increased systolic and diastolic blood pressure in a Chinese population. (PMID:25618516)
• While PMCA1b has a housekeeping function in colon cancer cells, PMCA4b participates in the reorganization of the calcium signaling machinery during cell differentiation. (PMID:26116539)
• Data show that plasma membrane Ca(2+)-ATPase (PMCA) was associated with tubulin in normotensive and hypertensive erythrocytes. (PMID:26307527)
• Crossover analysis and stratified analysis indicated that BMI has a major effect on the development of hypertension, while ATP2B1 variants have a minor effect (PMID:26933664)
• Excessive sodium intake significantly modified the risk of developing Hypertension associated with ATP2B1 rs17249754 genetic trait. Homozygote carriers may be at higher risk of hypertension, when they consume excessive sodium intake. (PMID:27149052)
• people with the major allele of ATP2B1 rs17249754 are susceptible to hypertension especially in low intake of Ca and high ratio of Na and K (PMID:28934190)
• enhanced eNOS activity induced by ATP2B1 gene silencing may be mediated via higher levels of intracellular Ca(2+), and the effect was confirmed to be dependent on the eNOS-calmodulin interaction (PMID:29416109)
• rs17249754-A (OR = 0.43, p = 0.0002) and rs1401982-G (OR = 0.47, p = 0.0007) were associated with decreased susceptibility of concurrent extra and intracranial stenosis even after Bonferroni correction. These two minor alleles were also significantly associated with less stenotic arteries and moderate-to-severe stenosis. (PMID:29902063)
• No significant association was found between ATP2B1 gene polymorphism and the odds of high blood pressure. (PMID:29982197)
• Cryoelectron microscopy reveals the PMCA1 structure in complex with neuroplastin. (PMID:30190470)
• ATP2B1 rs17249754 is positively associated with the risk of developing essential hypertension in patients from Burkina Faso, West Africa. (PMID:31242870)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp2b1b	ENSDARG00000007788
danio_rerio	atp2b1a	ENSDARG00000012684
mus_musculus	Atp2b1	ENSMUSG00000019943
rattus_norvegicus	Atp2b1	ENSRNOG00000004026
drosophila_melanogaster	anne	FBGN0052000
drosophila_melanogaster	SPoCk	FBGN0052451
drosophila_melanogaster	CG45062	FBGN0266432
drosophila_melanogaster	CG45063	FBGN0266433
caenorhabditis_elegans		WBGENE00000834
caenorhabditis_elegans	pmr-1	WBGENE00004063
caenorhabditis_elegans		WBGENE00012341
caenorhabditis_elegans		WBGENE00015338
caenorhabditis_elegans		WBGENE00015660

Paralogs (21): ATP2C1 (ENSG00000017260), ATP1A2 (ENSG00000018625), ATP2B4 (ENSG00000058668), ATP2C2 (ENSG00000064270), ATP2B3 (ENSG00000067842), ATP2A3 (ENSG00000074370), ATP12A (ENSG00000075673), ATP1A3 (ENSG00000105409), ATP4A (ENSG00000105675), ATP13A1 (ENSG00000105726), ATP7B (ENSG00000123191), ATP13A4 (ENSG00000127249), ATP1A4 (ENSG00000132681), ATP13A3 (ENSG00000133657), ATP2B2 (ENSG00000157087), ATP13A2 (ENSG00000159363), ATP1A1 (ENSG00000163399), ATP7A (ENSG00000165240), ATP2A2 (ENSG00000174437), ATP13A5 (ENSG00000187527), ATP2A1 (ENSG00000196296)

Protein

Protein identifiers

Plasma membrane calcium-transporting ATPase 1 — P20020 (reviewed: P20020)

Alternative names: Plasma membrane calcium ATPase isoform 1, Plasma membrane calcium pump isoform 1

All UniProt accessions (5): P20020, A0A0U1RQU3, A0A994J4Z0, F8W1V5, H0YHH6

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of ATP coupled with the transport of calcium from the cytoplasm to the extracellular space thereby maintaining intracellular calcium homeostasis. Plays a role in blood pressure regulation through regulation of intracellular calcium concentration and nitric oxide production leading to regulation of vascular smooth muscle cells vasoconstriction. Positively regulates bone mineralization through absorption of calcium from the intestine. Plays dual roles in osteoclast differentiation and survival by regulating RANKL-induced calcium oscillations in preosteoclasts and mediating calcium extrusion in mature osteoclasts. Regulates insulin sensitivity through calcium/calmodulin signaling pathway by regulating AKT1 activation and NOS3 activation in endothelial cells. May play a role in synaptic transmission by modulating calcium and proton dynamics at the synaptic vesicles.

Subunit / interactions. Monomer. Dimer. Oligomer. Calmodulin binding. Interacts with PDZD11. Interacts with SLC35G1 and STIM1; inhibits calcium-transporting ATPase activity after store depletion. Interacts with YWHAE; interacts with the monomeric and dimeric forms of the YWHAE but prefer the monomer form; this interaction inhibits calcium-transporting ATPase activity. Interacts with NPTN; this interaction stabilizes ATP2B1 and increases ATPase activity; this interaction controls T cell calcium homeostasis following T cell activation. Interacts with EPB41; regulates small intestinal calcium absorption through regulation of membrane expression of ATP2B1.

Subcellular location. Cell membrane. Basolateral cell membrane. Synapse. Presynaptic cell membrane. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane.

Tissue specificity. Isoform B: Ubiquitously expressed. Isoform C: Found in brain cortex, skeletal muscle and heart muscle. Isoform D: Has only been found in fetal skeletal muscle. Isoform K: Found in small intestine and liver. Abundantly expressed in the endometrial epithelial cells and glandular epithelial cells in early-proliferative phase and early-secretory phases.

Disease relevance. Intellectual developmental disorder, autosomal dominant 66 (MRD66) [MIM:619910] An autosomal dominant disorder characterized by mild to moderate global development delay, impaired intellectual development, and speech delay. Additional common symptoms include autism, seizures, and distal limb abnormalities. Disease severity is highly variable. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Isoforms A, C, D and E contain an additional calmodulin-binding subdomain B which is different in the different splice variants and shows pH dependent calmodulin binding properties.

Induction. Up-regulated at the proliferative phase of the mentrual cycle. Up-regulated by estrogen.

Similarity. Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIB subfamily.

Isoforms (6)

UniProt ID	Names	Canonical?
P20020-3	B, CI, hPMCA1b	yes
P20020-1	D, CIV, hPMCA1d
P20020-2	A, CII, hPMCA1a
P20020-4	C, CIII, hPMCA1c
P20020-5	E, CV
P20020-6	K

RefSeq proteins (30): NP_001001323, NP_001353449, NP_001353450, NP_001353451, NP_001353452, NP_001353453, NP_001353454, NP_001353455, NP_001353456, NP_001353457, NP_001353458, NP_001353459, NP_001353460, NP_001353461, NP_001399975, NP_001399976, NP_001399977, NP_001399978, NP_001399979, NP_001399980, NP_001399981, NP_001399982, NP_001399983, NP_001399984, NP_001399985, NP_001399986, NP_001399987, NP_001399988, NP_001399989, NP_001673 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001757	P_typ_ATPase	Family
IPR004014	ATPase_P-typ_cation-transptr_N	Domain
IPR006068	ATPase_P-typ_cation-transptr_C	Domain
IPR006408	P-type_ATPase_IIB	Family
IPR008250	ATPase_P-typ_transduc_dom_A_sf	Homologous_superfamily
IPR018303	ATPase_P-typ_P_site	PTM
IPR022141	ATP_Ca_trans_C	Domain
IPR023214	HAD_sf	Homologous_superfamily
IPR023298	ATPase_P-typ_TM_dom_sf	Homologous_superfamily
IPR023299	ATPase_P-typ_cyto_dom_N	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily
IPR044492	P_typ_ATPase_HD_dom	Domain
IPR059000	ATPase_P-type_domA	Domain

Pfam: PF00122, PF00689, PF00690, PF08282, PF12424, PF13246

Enzyme classification (BRENDA):

• EC 7.2.2.10 — P-type Ca2+ transporter (BRENDA: 47 organisms, 90 substrates, 341 inhibitors, 34 Km, 18 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CA2+	—	11
ATP	—	6
CA2+/CIS	0.0007–0.0013	3
CA2+[SIDE 1]	0.0002–0.0003	2
SR2+	0.015–0.035	2
UTP	—	1

Catalyzed reactions (Rhea), 1 shown:

• Ca(2+)(in) + ATP + H2O = Ca(2+)(out) + ADP + phosphate + H(+) (RHEA:18105)

UniProt features (66 total): sequence variant 15, topological domain 11, transmembrane region 10, modified residue 10, splice variant 6, region of interest 4, compositionally biased region 3, binding site 3, initiator methionine 1, chain 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6A69	ELECTRON MICROSCOPY	4.11

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20020-F1	74.76	0.21

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 475 (4-aspartylphosphate intermediate)

Ligand- & substrate-binding residues (3): 475; 477; 797

Post-translational modifications (10): 2, 8, 17, 338, 1116, 1140, 1155, 1165, 1178, 1182

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-418359	Reduction of cytosolic Ca++ levels
R-HSA-5578775	Ion homeostasis
R-HSA-936837	Ion transport by P-type ATPases
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea
R-HSA-109582	Hemostasis
R-HSA-382551	Transport of small molecules
R-HSA-397014	Muscle contraction
R-HSA-418346	Platelet homeostasis
R-HSA-418360	Platelet calcium homeostasis
R-HSA-5576891	Cardiac conduction
R-HSA-9659379	Sensory processing of sound
R-HSA-9709957	Sensory Perception
R-HSA-983712	Ion channel transport

MSigDB gene sets: 516 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, TAATAAT_MIR126, GOBP_REGULATION_OF_BLOOD_PRESSURE, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, TTTGTAG_MIR520D, DITTMER_PTHLH_TARGETS_UP, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS

GO Biological Process (16): negative regulation of cytokine production (GO:0001818), regulation of vascular associated smooth muscle contraction (GO:0003056), regulation of blood pressure (GO:0008217), positive regulation of bone mineralization (GO:0030501), monoatomic ion transmembrane transport (GO:0034220), regulation of cytosolic calcium ion concentration (GO:0051480), negative regulation of cytosolic calcium ion concentration (GO:0051481), positive regulation of calcium ion transport (GO:0051928), regulation of cellular response to insulin stimulus (GO:1900076), regulation of cardiac conduction (GO:1903779), calcium ion export across plasma membrane (GO:1990034), monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816), intracellular calcium ion homeostasis (GO:0006874), transmembrane transport (GO:0055085), calcium ion transmembrane transport (GO:0070588)

GO Molecular Function (10): P-type calcium transporter activity (GO:0005388), calmodulin binding (GO:0005516), ATP binding (GO:0005524), calcium ion transmembrane transporter activity (GO:0015085), ATP hydrolysis activity (GO:0016887), metal ion binding (GO:0046872), molecular function inhibitor activity (GO:0140678), nucleotide binding (GO:0000166), transporter activity (GO:0005215), protein binding (GO:0005515)

GO Cellular Component (13): immunological synapse (GO:0001772), nucleoplasm (GO:0005654), plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), synaptic vesicle membrane (GO:0030672), presynaptic membrane (GO:0042734), extracellular exosome (GO:0070062), photoreceptor ribbon synapse (GO:0098684), glutamatergic synapse (GO:0098978), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Platelet calcium homeostasis	1
Cardiac conduction	1
Ion channel transport	1
Sensory processing of sound	1
Hemostasis	1
Platelet homeostasis	1
Muscle contraction	1
Sensory Perception	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of biological quality	2
calcium ion transport	2
calcium ion transmembrane transport	2
transport	2
cytokine production	1
regulation of cytokine production	1
negative regulation of gene expression	1
negative regulation of multicellular organismal process	1
regulation of smooth muscle contraction	1
vascular associated smooth muscle contraction	1
regulation of vasoconstriction	1
blood circulation	1
bone mineralization	1
regulation of bone mineralization	1
positive regulation of ossification	1
positive regulation of biomineral tissue development	1
monoatomic ion transport	1
transmembrane transport	1
intracellular calcium ion homeostasis	1
positive regulation of monoatomic ion transport	1
regulation of calcium ion transport	1
cellular response to insulin stimulus	1
regulation of response to stimulus	1
regulation of cellular process	1
regulation of heart contraction	1
cardiac conduction	1
export across plasma membrane	1
metal ion transport	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
cellular process	1
monoatomic cation transmembrane transport	1
calcium ion transmembrane transporter activity	1
P-type ion transporter activity	1
ATPase-coupled monoatomic cation transmembrane transporter activity	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
metal ion transmembrane transporter activity	1

Protein interactions and networks

STRING

2456 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP2B1	TRPV6	Q9H1D0	863
ATP2B1	UBE3B	Q7Z3V4	779
ATP2B1	SLC8A1	P32418	752
ATP2B1	CALM1	P02593	723
ATP2B1	CALML3	P27482	717
ATP2B1	TRPV4	Q9HBA0	711
ATP2B1	CALML5	Q9NZT1	708
ATP2B1	CALML4	Q96GE6	705
ATP2B1	CALML6	Q8TD86	704
ATP2B1	TRPV5	Q9NQA5	677
ATP2B1	S100G	P29377	654
ATP2B1	NPTN	Q9Y639	620
ATP2B1	ATP2A2	P16614	569
ATP2B1	MTHFR	P42898	551
ATP2B1	ATP1B1	P05026	543

IntAct

262 interactions, top by confidence:

A	B	Type	Score
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
SCRIB	ATP2B1	psi-mi:“MI:0407”(direct interaction)	0.620
ATP2B1	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.620
SLC35G1	ATP2B1	psi-mi:“MI:0915”(physical association)	0.620
ATP2B1	SLC35G1	psi-mi:“MI:0915”(physical association)	0.620
YWHAZ	SHTN1	psi-mi:“MI:0914”(association)	0.530
HSD17B6	NME2P1	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
NPTN	TNPO2	psi-mi:“MI:0914”(association)	0.530
OPALIN	BTAF1	psi-mi:“MI:0914”(association)	0.530
ETS1	ETS1	psi-mi:“MI:0914”(association)	0.500
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
sseJ	NPC1	psi-mi:“MI:0914”(association)	0.460
vpu	SCAMP3	psi-mi:“MI:0914”(association)	0.460
ATP2B1	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
SNX27	ATP2B1	psi-mi:“MI:0407”(direct interaction)	0.440
ATP2B1	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
ATP2B1	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (337): ATP2B1 (Affinity Capture-MS), ATP2B1 (Affinity Capture-MS), ATP2B1 (Affinity Capture-MS), ATP2B1 (Affinity Capture-MS), ATP2B1 (Affinity Capture-RNA), ATP1A1 (Co-fractionation), ATP2B1 (Co-fractionation), ATP2B1 (Co-fractionation), ATP2B1 (Co-fractionation), CANX (Co-fractionation), CLGN (Co-fractionation), ATP2B1 (Affinity Capture-MS), ATP2B1 (Proximity Label-MS), ATP2B1 (Proximity Label-MS), ATP2B1 (Proximity Label-MS)

ESM2 similar proteins: A0A143ZZK9, A5IYF2, A6ZQM4, B3LQ11, B9QMJ0, B9WLN5, D3K0R6, G5E829, G5EFR6, J9VQQ3, O13397, O13398, P11505, P11506, P13586, P13587, P20020, P22189, P23220, P23634, P32660, P38929, P39677, P54678, P54679, P58165, Q00804, Q01814, Q01896, Q06698, Q12675, Q12691, Q16720, Q54L53, Q54SW3, Q54TV1, Q54TV2, Q55CP6, Q5A6N1, Q64542

Diamond homologs: A0A0P0X004, A0AM16, B0R9M0, B2TMJ2, B2V2P3, B8DAW1, C1KZN5, D3K0R6, G0S196, G5E829, G5EFR6, J9VQQ3, O22218, O29777, O31688, O32328, O54827, O60312, O64806, O81108, P11505, P11506, P20020, P23220, P23634, P28774, P35317, P37279, P37367, P38929, P38995, P54678, P57698, P57699, P57700, P58165, P58342, P86911, P9WPS2, P9WPS3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKACA	“up-regulates activity”	ATP2B1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 209 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	7	27.9×	2e-06
Long-term potentiation	6	20.0×	8e-05
Unblocking of NMDA receptors, glutamate binding and activation	5	19.0×	5e-04
Negative regulation of NMDA receptor-mediated neuronal transmission	5	19.0×	5e-04
Dopamine Neurotransmitter Release Cycle	5	17.4×	7e-04
Assembly and cell surface presentation of NMDA receptors	8	14.2×	2e-05
Neurexins and neuroligins	9	12.4×	2e-05
NCAM signaling for neurite out-growth	6	11.4×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	8	25.4×	8e-07
protein localization to synapse	5	20.9×	9e-04
receptor clustering	6	20.5×	3e-04
regulation of postsynaptic membrane neurotransmitter receptor levels	6	16.2×	5e-04
regulation of synaptic vesicle exocytosis	5	12.4×	5e-03
long-term synaptic potentiation	6	9.2×	5e-03
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	10	4.3×	8e-03
chemical synaptic transmission	10	4.2×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

279 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	26
Uncertain significance	194
Likely benign	11
Benign	5

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1679165	NM_001366521.1(ATP2B1):c.2632C>T (p.Gln878Ter)	Pathogenic
1703507	NM_001366521.1(ATP2B1):c.2570A>G (p.Gln857Arg)	Pathogenic
1706695	NM_001366521.1(ATP2B1):c.2230C>T (p.Arg744Ter)	Pathogenic
2112721	NM_001366521.1(ATP2B1):c.1370_1373del (p.Val457fs)	Pathogenic
2317380	NM_001366521.1(ATP2B1):c.2533G>T (p.Gly845Ter)	Pathogenic
2601163	NM_001366521.1(ATP2B1):c.2331del (p.Gly779fs)	Pathogenic
3376629	NM_001366521.1(ATP2B1):c.658del (p.Tyr220fs)	Pathogenic
3377230	NM_001366521.1(ATP2B1):c.2954del (p.Phe985fs)	Pathogenic
3603000	NM_001366521.1(ATP2B1):c.139C>T (p.Arg47Ter)	Pathogenic
3651904	NM_001366521.1(ATP2B1):c.20_21insG (p.Asn7fs)	Pathogenic
3768438	NM_001366521.1(ATP2B1):c.2443-2A>G	Pathogenic
3900597	NM_001366521.1(ATP2B1):c.1925C>A (p.Ser642Ter)	Pathogenic
4074397	NM_001366521.1(ATP2B1):c.937C>T (p.Gln313Ter)	Pathogenic
4082342	NM_001366521.1(ATP2B1):c.1339_1342del (p.Val447fs)	Pathogenic
4591037	NM_001366521.1(ATP2B1):c.333_337del (p.Leu111fs)	Pathogenic
4755753	NM_001366521.1(ATP2B1):c.559C>T (p.Arg187Ter)	Pathogenic
833258	NC_000012.12:g.(?88516334)(89591295_?)del	Pathogenic
1334402	NM_001366521.1(ATP2B1):c.3060+2T>G	Likely pathogenic
1334403	NM_001366521.1(ATP2B1):c.2938G>T (p.Val980Leu)	Likely pathogenic
1679159	NM_001366521.1(ATP2B1):c.716A>G (p.Asp239Gly)	Likely pathogenic
1679160	NM_001366521.1(ATP2B1):c.791C>T (p.Thr264Ile)	Likely pathogenic
1679161	NM_001366521.1(ATP2B1):c.1274C>A (p.Thr425Lys)	Likely pathogenic
1679163	NM_001366521.1(ATP2B1):c.2470G>A (p.Glu824Lys)	Likely pathogenic
1679166	NM_001366521.1(ATP2B1):c.458G>A (p.Trp153Ter)	Likely pathogenic
1684514	NM_001366521.1(ATP2B1):c.1907_1908del (p.Val636fs)	Likely pathogenic
2580931	NM_001366521.1(ATP2B1):c.2959G>T (p.Glu987Ter)	Likely pathogenic
2626973	NM_001366521.1(ATP2B1):c.406+1G>A	Likely pathogenic
2627844	NM_001366521.1(ATP2B1):c.3110C>G (p.Ser1037Ter)	Likely pathogenic
2631726	NM_001366521.1(ATP2B1):c.2482ATT[1] (p.Ile829del)	Likely pathogenic
2683828	NM_001366521.1(ATP2B1):c.2509_2512del (p.Ser837fs)	Likely pathogenic

SpliceAI

3507 predictions. Top by Δscore:

Variant	Effect	Δscore
12:89591294:ATC:A	acceptor_loss	1.0000
12:89591295:TCTG:T	acceptor_loss	1.0000
12:89591296:C:CC	acceptor_gain	1.0000
12:89591296:CTGTA:C	acceptor_loss	1.0000
12:89591297:T:A	acceptor_loss	1.0000
12:89599173:C:CA	donor_gain	1.0000
12:89599296:TAAG:T	acceptor_gain	1.0000
12:89604150:CCTA:C	donor_gain	1.0000
12:89604153:A:AC	donor_gain	1.0000
12:89604154:C:CT	donor_gain	1.0000
12:89604196:C:CT	donor_gain	1.0000
12:89604197:T:TC	donor_gain	1.0000
12:89604342:ATACC:A	acceptor_gain	1.0000
12:89604343:TACC:T	acceptor_gain	1.0000
12:89604344:ACCC:A	acceptor_loss	1.0000
12:89604345:CC:C	acceptor_gain	1.0000
12:89604346:CCTG:C	acceptor_gain	1.0000
12:89604347:C:CC	acceptor_gain	1.0000
12:89604348:T:A	acceptor_loss	1.0000
12:89609933:TTAC:T	donor_loss	1.0000
12:89609934:TAC:T	donor_loss	1.0000
12:89609935:A:AC	donor_gain	1.0000
12:89609935:AC:A	donor_gain	1.0000
12:89609935:ACC:A	donor_loss	1.0000
12:89609936:C:CA	donor_gain	1.0000
12:89609936:CC:C	donor_gain	1.0000
12:89609936:CCA:C	donor_gain	1.0000
12:89610039:TATAC:T	acceptor_gain	1.0000
12:89610041:TAC:T	acceptor_gain	1.0000
12:89610041:TACC:T	acceptor_loss	1.0000

AlphaMissense

8015 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:89591275:A:C	F1124L	1.000
12:89591275:A:T	F1124L	1.000
12:89591277:A:G	F1124L	1.000
12:89599149:A:G	W1107R	1.000
12:89599149:A:T	W1107R	1.000
12:89603131:C:G	R991P	1.000
12:89603175:A:C	F976L	1.000
12:89603175:A:T	F976L	1.000
12:89603177:A:G	F976L	1.000
12:89603828:A:G	L911P	1.000
12:89603855:A:G	L902P	1.000
12:89603855:A:T	L902Q	1.000
12:89603861:A:G	L900P	1.000
12:89603867:G:T	A898D	1.000
12:89603875:A:C	D895E	1.000
12:89603875:A:T	D895E	1.000
12:89603876:T:C	D895G	1.000
12:89603876:T:G	D895A	1.000
12:89603877:C:G	D895H	1.000
12:89603885:A:G	L892P	1.000
12:89603885:A:T	L892H	1.000
12:89603887:G:C	N891K	1.000
12:89603887:G:T	N891K	1.000
12:89603895:A:G	W889R	1.000
12:89603895:A:T	W889R	1.000
12:89603897:A:G	L888P	1.000
12:89603897:A:T	L888Q	1.000
12:89603915:A:T	L882H	1.000
12:89604172:C:G	G873R	1.000
12:89604200:A:C	N863K	1.000

dbSNP variants (sampled 300 via entrez): RS1000005941 (12:89635551 G>T), RS1000008928 (12:89637487 C>A,G), RS1000020556 (12:89684885 C>A), RS1000051988 (12:89708955 G>C), RS1000064993 (12:89668198 C>A), RS1000073866 (12:89680635 G>A), RS1000080932 (12:89630418 A>T), RS1000082361 (12:89673913 T>A), RS1000117198 (12:89678926 C>T), RS1000119369 (12:89671707 A>C), RS1000119703 (12:89609063 T>C), RS1000120518 (12:89588484 GA>G), RS1000141083 (12:89635991 A>G), RS1000153516 (12:89617905 T>C), RS1000161794 (12:89628915 T>C)

Disease associations

OMIM: gene MIM:108731 | disease phenotypes: MIM:119800, MIM:261800, MIM:300049, MIM:619910, MIM:616083, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder, autosomal dominant 66	Strong	Autosomal dominant

Mondo (7): clubfoot (MONDO:0007342), isolated Pierre-Robin syndrome (MONDO:0009869), periventricular nodular heterotopia (MONDO:0020341), intellectual developmental disorder, autosomal dominant 66 (MONDO:0030891), neurodevelopmental disorder (MONDO:0700092), intellectual disability, autosomal dominant 30 (MONDO:0014486), autism (MONDO:0005260)

Orphanet (6): Familial clubfoot with or without associated lower limb anomalies (Orphanet:199315), Isolated Pierre Robin sequence (Orphanet:718), Periventricular nodular heterotopia (Orphanet:98892), Intellectual disability-expressive aphasia-facial dysmorphism syndrome (Orphanet:436151), ZMYND11-related developmental delay-speech delay-seizures-behavioral abnormalities-craniofacial dysmorphism syndrome (Orphanet:694304), ZMYND11-related developmental delay-speech delay-seizures-behavioral abnormalities-craniofacial dysmorphism syndrome due to a point mutation (Orphanet:694308)

HPO phenotypes

24 total (25 of 24 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000248	Brachycephaly
HP:0000369	Low-set ears
HP:0000729	Autistic behavior
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0001166	Arachnodactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001357	Plagiocephaly
HP:0001669	Transposition of the great arteries
HP:0001684	Secundum atrial septal defect
HP:0001863	Toe clinodactyly
HP:0002616	Aortic root aneurysm
HP:0002650	Scoliosis
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0004209	Clinodactyly of the 5th finger
HP:0008070	Sparse hair
HP:0011463	Childhood onset
HP:0012469	Infantile spasms
HP:0033522	Cerebral cavernous malformation
HP:0000717	Autism

GWAS associations

157 associations (top):

Study	Trait	p-value
GCST000381_3	Biomedical quantitative traits	1.000000e-07
GCST000381_4	Biomedical quantitative traits	3.000000e-06
GCST000393_5	Systolic blood pressure	4.000000e-11
GCST000396_2	Diastolic blood pressure	1.000000e-09
GCST000398_2	Hypertension	2.000000e-11
GCST000756_5	Magnesium levels	1.000000e-16
GCST001072_9	Blood pressure	8.000000e-20
GCST001074_3	Blood pressure	2.000000e-13
GCST001235_6	Blood pressure	6.000000e-10
GCST001236_5	Blood pressure	1.000000e-17
GCST001587_3	Coronary heart disease	6.000000e-10
GCST002167_3	Blood pressure	7.000000e-15
GCST002497_20	Blood pressure	4.000000e-08
GCST002497_21	Blood pressure	2.000000e-07
GCST002627_11	Hypertension	2.000000e-08
GCST002630_12	Systolic blood pressure	4.000000e-12
GCST002631_2	Diastolic blood pressure	2.000000e-10
GCST003116_27	Coronary artery disease	6.000000e-11
GCST003117_20	Myocardial infarction	6.000000e-09
GCST003272_12	Systolic blood pressure	3.000000e-06
GCST003272_16	Systolic blood pressure	8.000000e-20
GCST003272_9	Systolic blood pressure	3.000000e-17
GCST003273_10	Diastolic blood pressure	5.000000e-13
GCST003273_6	Diastolic blood pressure	9.000000e-15
GCST003274_1	Pulse pressure	3.000000e-09
GCST003275_11	Mean arterial pressure	2.000000e-16
GCST004143_3	Hypertension	2.000000e-07
GCST004257_4	Systolic blood pressure (long-term average)	1.000000e-17
GCST004258_3	Diastolic blood pressure (long-term average)	1.000000e-17
GCST004259_4	Mean arterial pressure (long-term average)	1.000000e-17

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0004845	magnesium measurement
EFO:0005763	pulse pressure measurement
EFO:0006340	mean arterial pressure
EFO:0004838	calcium measurement
EFO:0004329	alcohol drinking
EFO:0006527	smoking status measurement
EFO:0007620	volumetric bone mineral density
EFO:0008579	risk-taking behaviour
EFO:0008328	chronotype measurement
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0009928	Diuretic use measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:1001483	non-obstructive coronary artery disease
EFO:0007986	reticulocyte count

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D003025	Clubfoot	C05.330.488.655.063; C05.330.495.681.063; C05.660.585.512.380.813.063; C16.131.621.585.512.500.681.063
D065886	Neurodevelopmental Disorders	F03.625
D054091	Periventricular Nodular Heterotopia	C10.500.507.450.750; C16.131.666.507.450.750
D010855	Pierre Robin Syndrome	C05.500.460.606; C05.660.207.540.460.606; C07.320.440.606; C07.650.500.460.606; C16.131.621.207.540.460.606; C16.131.850.500.460.606

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12817819	Efficacy	3	Antihypertensives	Coronary Artery Disease;Hypertension

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12817819	ATP2B1	3	1.75	1	Antihypertensives
rs17381194	ATP2B1		0.00	0
rs1401982	ATP2B1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — P2B P-type ATPases: Ca²⁺-ATPases

CTD chemical–gene interactions

91 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	5
Air Pollutants	decreases expression, affects expression, increases abundance, increases expression	3
Estradiol	decreases reaction, affects cotreatment, decreases expression	3
bisphenol A	decreases expression, increases expression	2
Arsenic Trioxide	decreases expression	2
Acetaminophen	increases expression	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Plant Extracts	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	decreases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	increases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tetrahydropalmatine	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects expression	1
sodium arsenite	affects expression	1
tetrabromobisphenol A	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	affects cotreatment, decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1KP	Abcam HeLa ATP2B1 KO	Cancer cell line	Female
CVCL_C7XX	HAP1 ATP2B1 (-) 1	Cancer cell line	Male
CVCL_C7XY	HAP1 ATP2B1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

255 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04564430	PHASE4	UNKNOWN	Clonidine for Tourniquet-related Pain in Children
NCT04766684	PHASE4	COMPLETED	Clubfoot Tenotomy Trial
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT02815215	EARLY_PHASE1	UNKNOWN	Efficacy Analysis of Minimally Invasive Carroll’s Technique in Treatment of Congenital Idiopathic Clubfoot
NCT00175708	Not specified	COMPLETED	Pedobarographic Assessments of Clubfoot Treated Patients
NCT00474032	Not specified	UNKNOWN	Using Botox to Treat Patients With Idiopathic Clubfoot
NCT00474344	Not specified	COMPLETED	Genetic Linkage Study of Idiopathic Talipes Equinovarus (ITEV) (Clubfoot)
NCT00475631	Not specified	WITHDRAWN	Economic Evaluation of Clubfoot Treatment: One Centre’s Experience
NCT00607191	Not specified	COMPLETED	Clubfoot DNA Repository
NCT01050088	Not specified	UNKNOWN	Sucrose Analgesia in Infants Undergoing Casting for Club Foot
NCT01067651	Not specified	COMPLETED	Comparison of Casting Materials for the Treatment of Clubfoot Using the Ponseti Method
NCT01088828	Not specified	COMPLETED	Exploring the Causes of Clubfoot Using Magnetic Resonance Imaging, MRI
NCT01481324	Not specified	COMPLETED	Outcomes of Compliance With Brace Wear in Clubfoot
NCT02022267	Not specified	COMPLETED	Gait Analysis in Ponseti Clubfoot
NCT02395185	Not specified	COMPLETED	A Randomized Controlled Trial of Three Non-pharmacologic Analgesic Techniques for Casting of Clubfoot Infants
NCT02815306	Not specified	COMPLETED	Polyaxial Brace Fixing for the Treatment of Congenital Clubfoot
NCT03249805	Not specified	UNKNOWN	MiracleFeet Foot Abduction Brace Sensor Trial
NCT03580746	Not specified	WITHDRAWN	Comparison of Ponseti Method Versus Older Treatments in Talipes Equinovarus Through Gait Analysis and Clinical Results
NCT03671863	Not specified	COMPLETED	Children Born With Club Feet
NCT03749265	Not specified	UNKNOWN	Rate Of Residual Clubfoot Deformity With Correlation To Absence Of Peroneus Tertius Muscle
NCT03853811	Not specified	TERMINATED	Customized Orthosis for Children With Clubfoot
NCT03953430	Not specified	COMPLETED	Gait Analysis in Children With Clubfoot Treated With Tibialis Anterior Tendon Transfer
NCT04212663	Not specified	UNKNOWN	A Study on the Treatment of Recurrent Clubfoot With the Tendon Release of Musculi Tibialis Posterior
NCT04693065	Not specified	UNKNOWN	Pronostic Factors of Long Term Outcome in Patients With Clubfoot Treated by the Ponseti Method
NCT04737083	Not specified	UNKNOWN	CGH Array in Bilateral Clubfoot
NCT04897100	Not specified	COMPLETED	Outcome After Needle vs Blade Achilles Tenotomy in Clubfoot
NCT05293743	Not specified	COMPLETED	Novel Dynamic Foot Abduction Bar for Treatment of Clubfoot
NCT05456737	Not specified	COMPLETED	Functional Assessment in Children With Clubfoot
NCT05767762	Not specified	RECRUITING	Evertor Muscle Activity as a Predictor of Achilles Tenotomy in the Management of Idiopathic Varus Equinus Clubfoot