ATP2A3

Summary

ATP2A3 (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3, HGNC:813) is a protein-coding gene on chromosome 17p13.2, encoding Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (Q93084). This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium.

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.

Source: NCBI Gene 489 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 211 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005173

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:813
Approved symbol	ATP2A3
Name	ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	SERCA3
Ensembl gene	ENSG00000074370
Ensembl biotype	protein_coding
OMIM	601929
Entrez	489

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 15 protein_coding, 7 retained_intron

ENST00000309890, ENST00000352011, ENST00000359983, ENST00000397035, ENST00000397041, ENST00000397043, ENST00000570773, ENST00000570845, ENST00000571245, ENST00000572116, ENST00000572176, ENST00000572694, ENST00000574202, ENST00000574999, ENST00000576957, ENST00000905320, ENST00000905321, ENST00000905322, ENST00000905323, ENST00000905324, ENST00000905325, ENST00000916223

RefSeq mRNA: 7 — MANE Select: NM_005173 NM_005173, NM_174953, NM_174954, NM_174955, NM_174956, NM_174957, NM_174958

CCDS: CCDS11041, CCDS11042, CCDS42234, CCDS45579, CCDS45580

Canonical transcript exons

ENST00000397041 — 21 exons

Exon	Start	End
ENSE00003462115	3944704	3944806
ENSE00003466219	3947391	3947855
ENSE00003476477	3943391	3943522
ENSE00003476805	3923873	3925441
ENSE00003491358	3953693	3953710
ENSE00003512535	3937416	3937636
ENSE00003516743	3936267	3936469
ENSE00003523994	3951251	3951389
ENSE00003533871	3945060	3945148
ENSE00003551375	3953347	3953429
ENSE00003556297	3950511	3950596
ENSE00003565108	3940971	3941306
ENSE00003571908	3951581	3951685
ENSE00003596849	3929328	3929445
ENSE00003604483	3950693	3950773
ENSE00003611696	3942606	3942731
ENSE00003621807	3930301	3930434
ENSE00003625424	3935192	3935277
ENSE00003628547	3941436	3941654
ENSE00003668246	3928663	3928780
ENSE00003850309	3964174	3964437

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 98.55.

FANTOM5 (CAGE): breadth broad, TPM avg 16.9649 / max 475.9939, expressed in 793 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163895	14.5770	735
163896	1.4325	410
163897	0.8787	356
163894	0.0767	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.55	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.12	gold quality
spleen	UBERON:0002106	97.11	gold quality
mucosa of transverse colon	UBERON:0004991	96.96	gold quality
nasal cavity mucosa	UBERON:0001826	96.63	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.27	gold quality
thymus	UBERON:0002370	96.25	gold quality
lymph node	UBERON:0000029	96.21	gold quality
blood	UBERON:0000178	96.13	gold quality
bone marrow cell	CL:0002092	95.87	gold quality
type B pancreatic cell	CL:0000169	95.61	gold quality
vermiform appendix	UBERON:0001154	95.50	gold quality
minor salivary gland	UBERON:0001830	95.00	gold quality
transverse colon	UBERON:0001157	94.98	gold quality
saliva-secreting gland	UBERON:0001044	94.87	gold quality
nasal cavity epithelium	UBERON:0005384	94.80	gold quality
rectum	UBERON:0001052	94.64	gold quality
small intestine	UBERON:0002108	94.57	gold quality
islet of Langerhans	UBERON:0000006	94.28	gold quality
tonsil	UBERON:0002372	94.15	gold quality
ileal mucosa	UBERON:0000331	93.81	gold quality
mucosa of stomach	UBERON:0001199	93.51	gold quality
leukocyte	CL:0000738	93.29	gold quality
monocyte	CL:0000576	93.07	gold quality
body of stomach	UBERON:0001161	93.06	gold quality
mononuclear cell	CL:0000842	92.92	gold quality
pancreas	UBERON:0001264	92.53	gold quality
body of pancreas	UBERON:0001150	92.51	gold quality
trachea	UBERON:0003126	92.39	gold quality
caecum	UBERON:0001153	92.13	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	16.63
E-GEOD-81608	yes	16.28
E-ENAD-27	yes	14.03
E-ANND-3	yes	13.34
E-GEOD-83139	yes	9.94
E-MTAB-8410	yes	5.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1, SP1, SP3

miRNA regulators (miRDB)

62 targeting ATP2A3, 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-6833-3P	100.00	70.63	3197
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084

Literature-anchored findings (GeneRIF, showing 31)

• novel sarco/endoplasmic isoforms; data suggest that the SERCA3 gene products have a more widespread role in cellular Ca2+ signaling than previously appreciated (PMID:11956212)
• SERCA3 constitutes an interesting new differentiation marker that may prove useful for the analysis of the phenotype of gastrointestinal adenocarcinomas. (PMID:11986315)
• Results describe the catalytic cycle of three human SERCA3 isoenzymes: SERCA3a, b, and c. (PMID:12207029)
• A method is described for a calcium-activated ATPase technique to be peformed. (PMID:12503734)
• monoclonal antibody PL/IM430 inhibits SERCA3 activity by sterically preventing movement of the actuator domain into a catalytically critical position in the E2 conformation of the enzyme. (PMID:12540840)
• SERCA3 isoforms have a more widespread role in cellular Ca(2+) signaling: analysis of SERCA3f isoform (PMID:15028735)
• link SERCA3 expression to the state of differentiation of colonic epithelial cells (PMID:15972967)
• By increasing the rate of Ca2+ sequestration, up-regulation of SERCA 3 counteracts the cytosolic increase in Ca2+ concentration. (PMID:16250893)
• SERCA1, 2, and 3 sensitivity to thapsigargin is dependent on a phenylalanine 256 to valine mutation (PMID:16410239)
• Data showed that overexpression of SERCA3b affected cell adhesion and SERCA3f overexpression resulted in an increase in endoplasmic reticulum stress markers. (PMID:16725111)
• found abnormal expression of both PMCA and SERCA-type CA2+-ATPases in platelets of patients with adolescent idiopathic scoliosis (PMID:16973504)
• These results suggest that SERCA2b and 3 modulate thrombin-stimulated store-operated Ca(2+)entry probably by direct interaction with the hTRPC1 channel in human platelets. (PMID:18068335)
• Ca2+ ATPase sarcoplasmic/endoplasmic reticulum calcium ATPase 3 are involved in an increased susceptibility to develop head and neck squamous cell carcinoma in humans. (PMID:18295663)
• These findings revisit the human heart’s Ca(2+)ATPase system and indicate that SERCA3f may account for the mechanism of endoplasmic reticulum stress in vivo in heart failure. (PMID:18947868)
• ATP2A3 gene is involved in cancer susceptibility. (PMID:19100511)
• two distinct SERCA3 fragmentation profiles sign the co-expression of SERCA3 proteins in two conformational states in platelet membranes. (PMID:19135027)
• affinity for Ca(2+) is inherently lower for SERCA3 expressed in situ than for other SERCA isoforms (PMID:19225163)
• Data show that low Ca2+-affinity SERCA3, and the high Ca2+-affinity SERCA2 enzymes are simultaneously expressed in B cells, and decreased SERCA3 expression during EBV-infection. (PMID:19650915)
• SERCA2 and SERCA3 isoforms have roles in the failing and failing human heart (PMID:19962989)
• High SERCA3 expression is associated with pathogenesis, invasion, metastasis of gastric carcinomas. (PMID:22948776)
• Loss of SERCA3 expression is associated with lung cancer. (PMID:23157274)
• The Ca2+-ATPase activity in cloned Plasmodiuim falciparum strain D6 protein is higher than in cloned strain W2 protein. The Ca2+-ATPase activity in isolates from malaria patients varied widely. (PMID:23235306)
• aberrant SERCA3 expression is closely linked to the adenoma-adenocarcinoma sequence and progression of colorectal carcinomas. (PMID:24213720)
• Normal choroid plexus epithelial cells express SERCA3 abundantly, SERCA3 expression is strongly decreased in papillomas, and is absent in choroid plexus carcinoma, while expression in hyperplastic epithelium is high, similarly to normal epithelium. (PMID:24224513)
• we make a comprehensive analysis of the current knowledge of the role of the SERCA pumps in the pathophysiology of insulin-dependent diabetes mellitus type 1 (TIDM) and type 2 (T2DM) in the heart and beta-cells in the pancreas (PMID:25270119)
• Sp1, Sp3, and Klf-4 transcription factors bind to ATP2A3 proximal promoter elements and regulate basal gene expression. The study showed that these factors participated in the increase of ATP2A3 expression during cancer cell differentiation. (PMID:27433831)
• Together, these data provide evidence for the interaction of Bcl-2 with SERCA3b in vitro and in cell culture, and for Bcl-2-dependent conformational and functional changes of SERCA3b. (PMID:27639965)
• ATP2A3 methylation was not altered between patients with type 2 diabetes and healthy men. Moreover, a glucose challenge did not alter ATP2A3 methylation. (PMID:28011458)
• Data show that the nucleotide sequence from -280 to -135 position is an ATP2A3 epigenetic regulatory CpG region. SERCA3 mRNA expression is decreased during gastric and colorectal carcinoma development and tumors with high SERCA3 expression are associated with increased overall survival. These results suggest an essential role for SERCA3 in the regulation of cellular identity and growth, through cellular Ca2+ management. (PMID:30657210)
• This study demonstrates that ATP2A3 might be one of the potential targets for salinomycin, which can inhibit Ca(2+) release and trigger ER stress to exert anti-cancer effects. (PMID:31023247)
• Sarco/endoplasmic reticulum calcium ATPase 3 (SERCA3) expression in gastrointestinal stromal tumours. (PMID:38184384)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp2a3	ENSDARG00000060978
mus_musculus	Atp2a3	ENSMUSG00000020788
rattus_norvegicus	Atp2a3	ENSRNOG00000017912
drosophila_melanogaster	SERCA	FBGN0263006
caenorhabditis_elegans		WBGENE00004736

Paralogs (21): ATP2C1 (ENSG00000017260), ATP1A2 (ENSG00000018625), ATP2B4 (ENSG00000058668), ATP2C2 (ENSG00000064270), ATP2B3 (ENSG00000067842), ATP2B1 (ENSG00000070961), 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

Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 — Q93084 (reviewed: Q93084)

Alternative names: Calcium pump 3

All UniProt accessions (3): Q93084, A0A0C4DGN1, A0A0C4DGN3

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with sarcolipin (SLN). Interacts with phospholamban (PLN). Interacts with myoregulin (MRLN). Interacts with DWORF. Interacts with VMP1. Interacts with TUNAR; the interaction occurs at low levels in low glucose conditions and is increased by high glucose levels.

Subcellular location. Nucleus membrane. Endoplasmic reticulum membrane. Sarcoplasmic reticulum membrane.

Tissue specificity. Found in most tissues. Most abundant in thymus, trachea, salivary gland, spleen, bone marrow, lymph node, peripheral leukocytes, pancreas and colon. Also detected in fetal tissues. Expressed in cell lineages of hematopoietic, epithelial, or embryonic origin and also expressed in several cancer cell lines.

Activity regulation. Inhibited by sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN).

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

Isoforms (7)

UniProt ID	Names	Canonical?
Q93084-2	SERCA3A, HuS3-II	yes
Q93084-1	SERCA3B
Q93084-3	SERCA3C, HuS3-IV
Q93084-4	SERCA3G, HuS3-I
Q93084-5	SERCA3E
Q93084-6	SERCA3D
Q93084-7	SERCA3F

RefSeq proteins (7): NP_005164, NP_777613, NP_777614, NP_777615, NP_777616, NP_777617, NP_777618 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001757	P_typ_ATPase	Family
IPR004014	ATPase_P-typ_cation-transptr_N	Domain
IPR005782	P-type_ATPase_IIA	Family
IPR006068	ATPase_P-typ_cation-transptr_C	Domain
IPR008250	ATPase_P-typ_transduc_dom_A_sf	Homologous_superfamily
IPR018303	ATPase_P-typ_P_site	PTM
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, PF13246

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (67 total): binding site 25, topological domain 11, transmembrane region 10, modified residue 6, splice variant 6, sequence conflict 3, region of interest 2, sequence variant 2, chain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q93084-F1	86.75	0.45

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): 351 (4-aspartylphosphate intermediate)

Ligand- & substrate-binding residues (25): 304; 305; 307; 309; 351; 353; 353; 442; 489; 515; 560; 625 …

Post-translational modifications (6): 1, 17, 19, 25, 415, 662

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-1912420	Pre-NOTCH Processing in Golgi
R-HSA-418359	Reduction of cytosolic Ca++ levels
R-HSA-5578775	Ion homeostasis
R-HSA-936837	Ion transport by P-type ATPases
R-HSA-109582	Hemostasis
R-HSA-157118	Signaling by NOTCH
R-HSA-162582	Signal Transduction
R-HSA-1912422	Pre-NOTCH Expression and Processing
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-983712	Ion channel transport

MSigDB gene sets: 340 (showing top): ELVIDGE_HYPOXIA_DN, REACTOME_SIGNALING_BY_NOTCH, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, MODULE_45, GOZGIT_ESR1_TARGETS_DN, MEF2_02, GOBP_MONOATOMIC_CATION_TRANSPORT, NKX62_Q2, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GATA6_01, MODULE_301, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_SYSTEM_PROCESS

GO Biological Process (9): calcium ion transport (GO:0006816), intracellular calcium ion homeostasis (GO:0006874), monoatomic ion transmembrane transport (GO:0034220), intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059), calcium ion transmembrane transport (GO:0070588), transport across blood-brain barrier (GO:0150104), calcium ion transport from cytosol to endoplasmic reticulum (GO:1903515), regulation of cardiac conduction (GO:1903779), monoatomic ion transport (GO:0006811)

GO Molecular Function (12): calcium channel regulator activity (GO:0005246), P-type calcium transporter activity (GO:0005388), ATP binding (GO:0005524), cysteine-type endopeptidase activator activity involved in apoptotic process (GO:0008656), calcium ion transmembrane transporter activity (GO:0015085), ATP hydrolysis activity (GO:0016887), calcium-dependent ATPase activity (GO:0030899), transmembrane transporter binding (GO:0044325), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), transporter activity (GO:0005215), protein binding (GO:0005515)

GO Cellular Component (9): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), sarcoplasmic reticulum (GO:0016529), organelle membrane (GO:0031090), platelet dense tubular network membrane (GO:0031095), nuclear membrane (GO:0031965), sarcoplasmic reticulum membrane (GO:0033017), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Pre-NOTCH Expression and Processing	1
Platelet calcium homeostasis	1
Cardiac conduction	1
Ion channel transport	1
Signal Transduction	1
Signaling by NOTCH	1
Hemostasis	1
Platelet homeostasis	1
Muscle contraction	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
calcium ion transmembrane transport	2
ATP-dependent activity	2
intracellular membrane-bounded organelle	2
organelle membrane	2
bounding membrane of organelle	2
metal ion transport	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
monoatomic ion transport	1
transmembrane transport	1
response to endoplasmic reticulum stress	1
intrinsic apoptotic signaling pathway	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
vascular transport	1
cytosol to endoplasmic reticulum transport	1
regulation of heart contraction	1
cardiac conduction	1
transport	1
calcium channel activity	1
ion channel regulator activity	1
calcium ion transmembrane transporter activity	1
P-type ion transporter activity	1
ATPase-coupled monoatomic cation transmembrane transporter activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
peptidase activator activity involved in apoptotic process	1
cysteine-type endopeptidase regulator activity involved in apoptotic process	1
metal ion transmembrane transporter activity	1
ribonucleoside triphosphate phosphatase activity	1
protein binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
cytoplasm	1
endomembrane system	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

2174 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP2A3	SLN	O00631	857
ATP2A3	PLN	P26678	798
ATP2A3	TRAM2	Q15035	766
ATP2A3	STIM1	Q13586	752
ATP2A3	GTF3C1	Q12789	689
ATP2A3	ORAI1	Q96D31	663
ATP2A3	SLC8A1	P32418	601
ATP2A3	ITPR1	Q14643	592
ATP2A3	TRPC6	Q9Y210	590
ATP2A3	ITPR3	Q14573	577
ATP2A3	ATXN2L	Q8WWM7	550
ATP2A3	ITPR2	Q14571	532
ATP2A3	RYR3	Q15413	527
ATP2A3	STIM2	Q9P246	495
ATP2A3	RYR2	Q92736	486

IntAct

131 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
GNAI3	RGS12	psi-mi:“MI:0914”(association)	0.640
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
KCNA5	TMEM223	psi-mi:“MI:0914”(association)	0.530
BTN2A1	POTEF	psi-mi:“MI:0914”(association)	0.530
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
MCOLN3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
TSPAN17	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
EVA1C	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
KCNS3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
LRRTM1	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
CNGA3	C2CD2L	psi-mi:“MI:0914”(association)	0.530
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
VSIG1	TNPO2	psi-mi:“MI:0914”(association)	0.530
PIEZO1	CLGN	psi-mi:“MI:0914”(association)	0.530
SYT12	B4GALT5	psi-mi:“MI:0914”(association)	0.530
LRRC8B	SLC25A17	psi-mi:“MI:0914”(association)	0.530
TREML2	SNX2	psi-mi:“MI:0914”(association)	0.530
TMED6	SMPD2	psi-mi:“MI:0914”(association)	0.530
HTR3E	ARL6IP5	psi-mi:“MI:0914”(association)	0.530
SRPRB	CTDNEP1	psi-mi:“MI:0914”(association)	0.530
CST7	CTSL	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
CD40	EXOC5	psi-mi:“MI:0914”(association)	0.530

BioGRID (288): BCL2 (Affinity Capture-Luminescence), ATP2A3 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS)

ESM2 similar proteins: A1A4J6, D4ABB8, F1Q4S1, G5EBH1, O14072, O43520, O43861, O70228, O75110, P09626, P19156, P20648, P27112, P40527, P50996, P57792, P90747, P98195, P98196, P98197, P98198, P98199, Q10309, Q27533, Q3TYU2, Q4VNC1, Q4WYP6, Q5XF89, Q5XF90, Q5ZKB7, Q64436, Q6DFW5, Q8NB49, Q92126, Q93084, Q95JN5, Q9EPE9, Q9H7F0, Q9HD20, Q9LI83

Diamond homologs: A0A143ZZK9, A2VDL6, A7L9Z8, B9QMJ0, D2WKD8, O13397, O13398, O14983, O23087, O34431, O46674, O55143, O75185, O77696, P04074, P04191, P05023, P06685, P07038, P09572, P09626, P09627, P11507, P11607, P11718, P12522, P13585, P13586, P16615, P17326, P18596, P18907, P19156, P20431, P20647, P20648, P22189, P22700, P25489, P27112

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ETS1	“up-regulates quantity by expression”	ATP2A3	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	135
Likely benign	33
Benign	25

Top pathogenic / likely-pathogenic (0)

SpliceAI

3942 predictions. Top by Δscore:

Variant	Effect	Δscore
17:3928659:TCA:T	donor_loss	1.0000
17:3928660:CACCG:C	donor_loss	1.0000
17:3928661:A:AC	donor_gain	1.0000
17:3928661:ACCGT:A	donor_loss	1.0000
17:3928662:C:CC	donor_gain	1.0000
17:3928662:C:CG	donor_loss	1.0000
17:3928662:CCGTG:C	donor_gain	1.0000
17:3928776:ATGAG:A	acceptor_gain	1.0000
17:3928777:TGAG:T	acceptor_gain	1.0000
17:3928778:GAG:G	acceptor_gain	1.0000
17:3928779:AG:A	acceptor_gain	1.0000
17:3928781:C:CC	acceptor_gain	1.0000
17:3928785:C:CT	acceptor_gain	1.0000
17:3929326:A:AC	donor_gain	1.0000
17:3929327:C:CC	donor_gain	1.0000
17:3929444:CG:C	acceptor_gain	1.0000
17:3930446:G:C	acceptor_gain	1.0000
17:3930450:C:CT	acceptor_gain	1.0000
17:3930455:C:CT	acceptor_gain	1.0000
17:3935191:CCAG:C	donor_gain	1.0000
17:3935276:CA:C	acceptor_gain	1.0000
17:3935278:C:CC	acceptor_gain	1.0000
17:3936263:TCACC:T	donor_loss	1.0000
17:3936264:CAC:C	donor_loss	1.0000
17:3936265:A:AC	donor_gain	1.0000
17:3936265:ACCT:A	donor_gain	1.0000
17:3936266:C:CC	donor_gain	1.0000
17:3936266:CCT:C	donor_gain	1.0000
17:3936266:CCTC:C	donor_gain	1.0000
17:3937465:T:TA	donor_gain	1.0000

AlphaMissense

6461 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:3937617:T:G	D707A	1.000
17:3937619:G:C	N706K	1.000
17:3937619:G:T	N706K	1.000
17:3937626:C:T	G704E	1.000
17:3941019:C:A	K684N	1.000
17:3941019:C:G	K684N	1.000
17:3942690:G:C	F487L	1.000
17:3942690:G:T	F487L	1.000
17:3942692:A:G	F487L	1.000
17:3947434:T:G	D351A	1.000
17:3947435:C:G	D351H	1.000
17:3936401:A:G	L797P	0.999
17:3936403:G:C	N796K	0.999
17:3936403:G:T	N796K	0.999
17:3936411:A:G	W794R	0.999
17:3936411:A:T	W794R	0.999
17:3936413:A:T	L793H	0.999
17:3937485:C:G	R751P	0.999
17:3937501:C:G	A746P	0.999
17:3937581:G:T	A719D	0.999
17:3937597:C:G	A714P	0.999
17:3937605:A:G	L711P	0.999
17:3937616:G:C	D707E	0.999
17:3937616:G:T	D707E	0.999
17:3937617:T:A	D707V	0.999
17:3937617:T:C	D707G	0.999
17:3937618:C:G	D707H	0.999
17:3937627:C:G	G704R	0.999
17:3937627:C:T	G704R	0.999
17:3937629:T:A	D703V	0.999

dbSNP variants (sampled 300 via entrez): RS1000002237 (17:3947595 CT>C), RS1000081932 (17:3938905 C>T), RS1000102237 (17:3953081 G>A,C), RS1000246036 (17:3933810 G>A), RS1000305152 (17:3931749 C>T), RS1000450548 (17:3963977 C>T), RS1000457153 (17:3936678 G>C,T), RS1000491874 (17:3929514 G>A), RS1000521363 (17:3927011 C>A,G), RS1000551788 (17:3924530 A>T), RS1000646616 (17:3924639 C>T), RS1000666622 (17:3953513 G>A,T), RS1000874924 (17:3948536 C>A), RS1000947420 (17:3958162 C>G), RS1000950161 (17:3923403 G>A)

Disease associations

OMIM: gene MIM:601929 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002726_63	Glucose homeostasis traits	3.000000e-06
GCST007094_200	Diastolic blood pressure	1.000000e-08
GCST007430_60	Peak expiratory flow	2.000000e-08
GCST007431_56	Lung function (FEV1/FVC)	7.000000e-24
GCST009391_1905	Metabolite levels	3.000000e-06
GCST010002_118	Refractive error	6.000000e-14
GCST010241_232	Apolipoprotein A1 levels	2.000000e-09
GCST90026416_14	Mild age-related type 2 diabetes	5.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006831	acute insulin response measurement
EFO:0006336	diastolic blood pressure
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0010463	asymmetric dimethylarginine measurement
EFO:0004614	apolipoprotein A 1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2401 (SINGLE PROTEIN), CHEMBL3831290 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 93,882 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL140	CURCUMIN	3	93,882

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — P2A P-type ATPases: Ca²⁺-ATPases

ChEMBL bioactivities

6 potent at pChembl≥5 of 6 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.05	IC50	90	nM	CHEMBL468766
6.68	IC50	210	nM	CHEMBL4534285
5.70	IC50	2000	nM	CHEMBL480626
5.30	IC50	5000	nM	PAXILLINE
5.16	IC50	7000	nM	CURCUMIN
5.07	Ki	8600	nM	CURCUMIN

PubChem BioAssay actives

6 with measured affinity, of 6 total; 5 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2R,3S,5Z,9R)-5-(1-hydroxyethylidene)-8,8-dimethyl-7,16-diazapentacyclo[9.6.1.02,9.03,7.015,18]octadeca-1(17),11(18),12,14-tetraene-4,6-dione	1605041: Inhibition of human SERCA3a expressed in COS7 cells microsomal membranes preincubated for 10 mins followed by addition of ATP and measured after 40 mins by ELISA method	ic50	0.0900	uM
[(3S,3aR,4S,6R,6aR,7S,8S,9bS)-6-acetyloxy-4-butanoyloxy-3,3a-dihydroxy-3,6,9-trimethyl-8-[(Z)-2-methylbut-2-enoyl]oxy-2-oxo-4,5,6a,7,8,9b-hexahydroazuleno[4,5-b]furan-7-yl] octanoate	1605041: Inhibition of human SERCA3a expressed in COS7 cells microsomal membranes preincubated for 10 mins followed by addition of ATP and measured after 40 mins by ELISA method	ic50	0.2100	uM
2,5-ditert-butylbenzene-1,4-diol	1605041: Inhibition of human SERCA3a expressed in COS7 cells microsomal membranes preincubated for 10 mins followed by addition of ATP and measured after 40 mins by ELISA method	ic50	2.0000	uM
(1S,2R,5S,7R,11S,14S)-11-hydroxy-7-(2-hydroxypropan-2-yl)-1,2-dimethyl-6-oxa-23-azahexacyclo[12.10.0.02,11.05,10.016,24.017,22]tetracosa-9,16(24),17,19,21-pentaen-8-one	1605060: Inhibition of SERCA3 in human platelet microsomes by enzyme-coupled method	ic50	5.0000	uM
Curcumin	1605060: Inhibition of SERCA3 in human platelet microsomes by enzyme-coupled method	ic50	7.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects expression	4
Estradiol	affects reaction, decreases expression, affects cotreatment, increases expression	3
bisphenol A	affects reaction, decreases expression, decreases methylation	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
entinostat	increases expression, affects cotreatment	2
Resveratrol	affects cotreatment, decreases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, increases methylation	2
GSK-J4	decreases expression	1
sotorasib	affects cotreatment, decreases expression	1
propionaldehyde	increases expression	1
trichostatin A	affects expression, decreases reaction	1
16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
benzo(e)pyrene	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
bisphenol S	affects cotreatment, increases methylation	1
jinfukang	affects cotreatment, decreases expression, increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Benztropine	increases expression	1
Cadmium	increases expression	1
Calcitriol	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4404230	Binding	Inhibition of human SERCA3a expressed in COS7 cells microsomal membranes preincubated for 10 mins followed by addition of ATP and measured after 40 mins by ELISA method	Sarco/Endoplasmic Reticulum Calcium ATPase Inhibitors: Beyond Anticancer Perspective. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7KT	Ubigene A-549 ATP2A3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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