ATP2A1

Summary

ATP2A1 (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1, HGNC:811) is a protein-coding gene on chromosome 16p11.2, encoding Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (O14983). Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum.

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 muscular excitation and contraction. Mutations in this gene cause some autosomal recessive forms of Brody disease, characterized by increasing impairment of muscular relaxation during exercise. Alternative splicing results in three transcript variants encoding different isoforms.

Source: NCBI Gene 487 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Brody myopathy (Strong, GenCC)
• GWAS associations: 42
• Clinical variants (ClinVar): 980 total — 76 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 19
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_004320

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:811
Approved symbol	ATP2A1
Name	ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	SERCA1
Ensembl gene	ENSG00000196296
Ensembl biotype	protein_coding
OMIM	108730
Entrez	487

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000357084, ENST00000395503, ENST00000536376, ENST00000562185, ENST00000563975, ENST00000564112, ENST00000564470, ENST00000564732, ENST00000565042, ENST00000971325, ENST00000971326, ENST00000971327, ENST00000971328, ENST00000971329

RefSeq mRNA: 3 — MANE Select: NM_004320 NM_001286075, NM_004320, NM_173201

CCDS: CCDS10643, CCDS42139, CCDS66997

Canonical transcript exons

ENST00000395503 — 23 exons

Exon	Start	End
ENSE00001237135	28903323	28903440
ENSE00001237140	28903030	28903147
ENSE00001237145	28902778	28902911
ENSE00001237149	28902580	28902665
ENSE00001237153	28902184	28902386
ENSE00001237165	28900581	28900916
ENSE00001237188	28894505	28894607
ENSE00001237192	28894155	28894243
ENSE00001237197	28888787	28888953
ENSE00001237204	28887425	28887722
ENSE00001237210	28887189	28887274
ENSE00001237229	28879501	28879583
ENSE00001403134	28878488	28878789
ENSE00001521894	28903700	28903741
ENSE00001652278	28879099	28879116
ENSE00001676802	28901863	28902083
ENSE00001805227	28884575	28884655
ENSE00002593016	28904180	28904466
ENSE00003508882	28880915	28881019
ENSE00003602172	28882451	28882589
ENSE00003611775	28894822	28894953
ENSE00003625287	28898000	28898125
ENSE00003680626	28898233	28898451

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 99.86.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 19.9807 / max 4992.9618, expressed in 141 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153419	19.3834	128
153418	0.2562	24
153435	0.0690	16
153426	0.0561	14
153425	0.0524	12
153433	0.0473	14
153424	0.0331	14
153427	0.0245	6
153434	0.0232	12
153432	0.0205	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	99.86	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.81	gold quality
diaphragm	UBERON:0001103	99.78	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.77	gold quality
vastus lateralis	UBERON:0001379	99.72	gold quality
quadriceps femoris	UBERON:0001377	99.71	gold quality
triceps brachii	UBERON:0001509	99.70	gold quality
biceps brachii	UBERON:0001507	99.68	gold quality
skeletal muscle tissue	UBERON:0001134	99.62	gold quality
gastrocnemius	UBERON:0001388	99.56	gold quality
body of tongue	UBERON:0011876	99.42	gold quality
gluteal muscle	UBERON:0002000	99.38	gold quality
deltoid	UBERON:0001476	98.64	gold quality
muscle organ	UBERON:0001630	98.38	gold quality
tibialis anterior	UBERON:0001385	98.28	gold quality
muscle of leg	UBERON:0001383	97.88	gold quality
tongue	UBERON:0001723	92.68	gold quality
muscle tissue	UBERON:0002385	92.25	gold quality
pharyngeal mucosa	UBERON:0000355	90.96	gold quality
superior surface of tongue	UBERON:0007371	87.99	gold quality
right testis	UBERON:0004534	87.20	gold quality
left testis	UBERON:0004533	86.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.19	gold quality
mucosa of transverse colon	UBERON:0004991	83.78	gold quality
testis	UBERON:0000473	83.15	gold quality
right uterine tube	UBERON:0001302	81.21	gold quality
right lobe of liver	UBERON:0001114	79.37	gold quality
vena cava	UBERON:0004087	79.22	gold quality
minor salivary gland	UBERON:0001830	78.95	gold quality
adenohypophysis	UBERON:0002196	78.61	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYOG

miRNA regulators (miRDB)

33 targeting ATP2A1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-1248	98.47	67.54	1314
HSA-MIR-624-3P	98.37	67.06	1067
HSA-MIR-4782-5P	98.35	69.33	1474
HSA-MIR-5706	98.35	69.33	1463
HSA-MIR-92A-1-5P	98.28	64.51	631
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-7154-3P	97.65	65.02	985
HSA-MIR-597-5P	96.82	67.57	732

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 32)

• Modeling of the inhibitory interaction of phospholamban with the Ca2+ ATPase. (PMID:12525698)
• regulation by sarcolipin’s involvement in binding to transmembrane helices alone or in association with phospholamban (PMID:12692302)
• kinetic analysis of SERCA1 and SERCA2 isoforms and the effects of mutation (PMID:12975374)
• The coexistence of SERCA1 and -2, together with complex mixtures of MyHCs in most of the fibers provide the human EOMs with a unique molecular portfolio that allows a highly specific fine-tuning regimen of contraction and relaxation. (PMID:14638697)
• The combination of these histological and immunoblot results is consistent with the hypothesis that diaphragm remodeling elicited by severe COPD is characterized by a fast-to-slow SERCA isoform transformation. (PMID:15718407)
• SERCA1 gene transfer increased fractional myocardial cell shortening (compared to LacZ) and accelerated relengthening kinetics. (PMID:15767202)
• We suggest that aberrant splicing of SERCA1 mRNAs might contribute to impaired Ca2+ homeostasis in DM1 muscle (PMID:15972723)
• The maximal turnover rates of the ATPase activity for SPCA1 isoforms were 4.7-6.4-fold lower than that of SERCA1a (lowest for the shortest SPCA1a isoform). (PMID:16192278)
• SERCA1, 2, and 3 sensitivity to thapsigargin is dependent on a phenylalanine 256 to valine mutation (PMID:16410239)
• a functional abnormality in SERCA1 may have a role in inferior oblique overaction, an ocular motor disorder (PMID:16642550)
• Preload stimulates SERCA expression. BNP antagonizes this mechanism. Inhibition of cGMP-dependent protein kinase restored preload-dependent SERCA upregulation in the presence of recombinant human BNP. (PMID:16754798)
• 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)
• Our studies point to an important regulation of SERCA1b expression at the protein level and hints to a role in the growth of the developing muscle. (PMID:17010426)
• Overexpression of the CUG repeat expansion of DMPK mRNA resulted in exclusion of exon 22 of SERCA1. (PMID:17728322)
• Ca (2+) binding to Site I of SERCA1a in fact slightly reduces Trp fluorescence, and consequently that the rise in this fluorescence generally observed when two Ca (2+) ions bind to WT SERCA1a mainly reflects Ca (2+) binding at Site II of SERCA1a. (PMID:18947188)
• the increase in mechanical efficiency of cycling occurring during first weeks of endurance training may be due to down-regulation of SERCA pumps (PMID:18953100)
• The truncated variant of the sarcoendoplasmic reticulum Ca(2+)-ATPase 1 (S1T) amplifies endoplasmic reticulum stress through the PERK-eIF2alpha-ATF4-CHOP pathway. (PMID:19061639)
• Differential SERCA1a S-nitrosylation and SERCA1a/2a co-expression in subsets of slow myofibers should be considered as signs of an altered cytosolic Ca(2+) homeostasis following chronic muscle disuse (PMID:19644701)
• both topology and function of PLN are shaped by the interactions with lipids, which fine-tune the regulation of SERCA (PMID:21576492)
• These results indicate that PKC signaling is involved in the splicing of SERCA1 and provide new evidence for a link between alternative splicing and PKC signaling. (PMID:22609207)
• Aberrant splicing of SERCA1 may alter intracellular Ca(2+) signalling in myotonic dystrophy 1 and 2 myotubes. The differing dysregulation of intracellular Ca(2+) handling in DM1 and DM2 may explain their distinct sarcolemmal hyperexcitabilities. (PMID:23888875)
• We performed a detailed study of SERCA1 protein expression in muscle of patients with BD and BS, and evaluated the alternative splicing of SERCA1 in primary cultures of normal human muscle (PMID:23911890)
• We conclude that PLB C-terminal residues are critical for localization, oligomerization, and regulatory function. In particular, the PLB C terminus is an important determinant of the quaternary structure of the SERCA regulatory complex. (PMID:25074938)
• Thus the human SERCA1b has a different expression pattern from that of rodents and it is associated with DM2. (PMID:25487304)
• Formalin evokes calcium transients from the endoplasmatic reticulum via SERCA1-dependent, TRPA1-independent mechanism that may underlie formaldehyde-induced pan-neuronal excitation and subsequent inflammation. (PMID:25875358)
• The sphingolipid sphingosine increases the [Ca(2+)]i by inhibiting the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), in a similar manner to thapsigargin (Tg), a specific inhibitor of this Ca(2+) pump. (PMID:27033604)
• CAPN3 deficiency leads to degradation of SERCA proteins and Ca2+ dysregulation in the skeletal muscle. (PMID:27055500)
• Study demonstrated that (a) the distribution and the expression levels of total SERCA1 and SERCA2, the activity of SR Ca2+ ATPase, and the oligomerization of SERCA1 are similar in patients with myotonic dystrophy 1, myotonic dystrophy 2, hypothyroid myopathy and control subjects; and (b) SERCA1b is expressed in patients with myotonic dystrophy, mainly in myotonic dystrophy 2 muscles. (PMID:27133661)
• These results suggest that sAnk1 interacts with SLN both directly and in complex with SERCA1 and reduces SLN’s inhibitory effect on SERCA1 activity. (PMID:28487373)
• Atomistic Structure and Dynamics of the Ca(2+)-ATPase Bound to Phosphorylated Phospholamban. (PMID:33019581)
• Crosstalk among Calcium ATPases: PMCA, SERCA and SPCA in Mental Diseases. (PMID:33801794)
• Sorcin Activates the Brain PMCA and Blocks the Inhibitory Effects of Molecular Markers of Alzheimer’s Disease on the Pump Activity. (PMID:34205207)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Atp2a1	ENSMUSG00000030730
rattus_norvegicus	Atp2a1	ENSRNOG00000047124
drosophila_melanogaster	SPoCk	FBGN0052451
drosophila_melanogaster	CG45062	FBGN0266432
drosophila_melanogaster	CG45063	FBGN0266433
caenorhabditis_elegans		WBGENE00000834
caenorhabditis_elegans	pmr-1	WBGENE00004063
caenorhabditis_elegans		WBGENE00015338
caenorhabditis_elegans		WBGENE00015660

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

Protein

Protein identifiers

Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 — O14983 (reviewed: O14983)

Alternative names: Calcium pump 1, Calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform, Endoplasmic reticulum class 1/2 Ca(2+) ATPase

All UniProt accessions (6): O14983, H3BTF1, H3BTW4, H3BUT9, H3BUU3, H3BVB2

UniProt curated annotations — full annotation on UniProt →

Function. Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic 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.

Subcellular location. Endoplasmic reticulum membrane. Sarcoplasmic reticulum membrane.

Tissue specificity. Skeletal muscle, fast twitch muscle (type II) fibers.

Disease relevance. Brody disease (BROD) [MIM:601003] An autosomal recessive muscular disorder characterized by exercise-induced muscle stiffness and cramps primarily affecting the arms, legs, and eyelids, although more generalized muscle involvement may also occur. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by sarcolipin (SLN) and myoregulin (MRLN). Has also been shown to be reversibly inhibited by phospholamban (PLN) at low calcium concentrations in vitro. Dephosphorylated PLN decreases the apparent affinity of the ATPase for calcium and this inhibition is regulated by the phosphorylation of PLN in vitro. Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN).

Domain organisation. Ca(2+) and ATP binding cause major rearrangements of the cytoplasmic and transmembrane domains. According to the E1-E2 model, Ca(2+) binding to the cytosolic domain of the pump in the high-affinity E1 conformation is followed by the ATP-dependent phosphorylation of the active site Asp, giving rise to E1P. A conformational change of the phosphoenzyme gives rise to the low-affinity E2P state that exposes the Ca(2+) ions to the lumenal side and promotes Ca(2+) release. Dephosphorylation of the active site Asp mediates the subsequent return to the E1 conformation. PLN and SLN both have a single transmembrane helix; both occupy a similar binding site on ATP2A1 that is situated between the ATP2A1 transmembrane helices.

Induction. Increased contractile activity leads to a decrease in SERCA1 expression, while decreased contractile activity leads to an increase in SERCA1 expression.

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

Isoforms (3)

UniProt ID	Names	Canonical?
O14983-1	SERCA1B, ATP2A1B, Neonatal	yes
O14983-2	SERCA1A, ATP2A1A, Adult
O14983-3	3

RefSeq proteins (3): NP_001273004, NP_004311, NP_775293 (=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 (46 total): binding site 25, transmembrane region 10, modified residue 3, region of interest 2, splice variant 2, chain 1, active site 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14983-F1	88.65	0.56

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 (3): 441, 569, 581

Disulfide bonds (1): 876–888

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: 267 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, REACTOME_SIGNALING_BY_NOTCH, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_POSITIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, HUMMERICH_BENIGN_SKIN_TUMOR_DN, HUMMERICH_MALIGNANT_SKIN_TUMOR_DN, GOBP_MULTICELLULAR_ORGANISMAL_MOVEMENT, GOBP_SKELETAL_MUSCLE_CONTRACTION, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_MITOCHONDRIAL_CALCIUM_ION_HOMEOSTASIS, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_TRANSPORT

GO Biological Process (22): calcium ion transport (GO:0006816), intracellular calcium ion homeostasis (GO:0006874), regulation of striated muscle contraction (GO:0006942), apoptotic mitochondrial changes (GO:0008637), positive regulation of fast-twitch skeletal muscle fiber contraction (GO:0031448), positive regulation of endoplasmic reticulum calcium ion concentration (GO:0032470), negative regulation of endoplasmic reticulum calcium ion concentration (GO:0032471), monoatomic ion transmembrane transport (GO:0034220), response to endoplasmic reticulum stress (GO:0034976), negative regulation of striated muscle contraction (GO:0045988), positive regulation of mitochondrial calcium ion concentration (GO:0051561), maintenance of mitochondrion location (GO:0051659), intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059), calcium ion import (GO:0070509), calcium ion transmembrane transport (GO:0070588), relaxation of skeletal muscle (GO:0090076), positive regulation of cardiac muscle cell contraction (GO:0106134), positive regulation of ATPase-coupled calcium transmembrane transporter activity (GO:1901896), positive regulation of calcium ion import into sarcoplasmic reticulum (GO:1902082), regulation of cardiac conduction (GO:1903779), calcium ion import into sarcoplasmic reticulum (GO:1990036), monoatomic ion transport (GO:0006811)

GO Molecular Function (10): P-type calcium transporter activity (GO:0005388), calcium ion binding (GO:0005509), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), calcium-dependent ATPase activity (GO:0030899), protein homodimerization activity (GO:0042803), nucleotide binding (GO:0000166), transporter activity (GO:0005215), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (12): mitochondrion (GO:0005739), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), membrane (GO:0016020), sarcoplasmic reticulum (GO:0016529), platelet dense tubular network membrane (GO:0031095), H zone (GO:0031673), I band (GO:0031674), sarcoplasmic reticulum membrane (GO:0033017), calcium channel complex (GO:0034704), perinuclear region of cytoplasm (GO:0048471), endoplasmic reticulum (GO:0005783)

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
cytoplasm	4
cellular anatomical structure	4
intracellular membrane-bounded organelle	3
striated muscle contraction	2
endoplasmic reticulum calcium ion homeostasis	2
calcium ion transport	2
ATP-dependent activity	2
bounding membrane of organelle	2
metal ion transport	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
regulation of muscle contraction	1
apoptotic process	1
mitochondrion organization	1
fast-twitch skeletal muscle fiber contraction	1
regulation of fast-twitch skeletal muscle fiber contraction	1
positive regulation of striated muscle contraction	1
monoatomic ion transport	1
transmembrane transport	1
cellular response to stress	1
regulation of striated muscle contraction	1
negative regulation of muscle contraction	1
mitochondrial calcium ion homeostasis	1
mitochondrion localization	1
maintenance of organelle location	1
response to endoplasmic reticulum stress	1
intrinsic apoptotic signaling pathway	1
monoatomic cation transmembrane transport	1
relaxation of muscle	1
cardiac muscle cell contraction	1
regulation of cardiac muscle cell contraction	1
positive regulation of actin filament-based movement	1
P-type calcium transporter activity	1
positive regulation of ion transmembrane transporter activity	1
positive regulation of ATP-dependent activity	1
regulation of ATPase-coupled calcium transmembrane transporter activity	1
positive regulation of intracellular transport	1
positive regulation of calcium ion transport	1
regulation of calcium ion import into sarcoplasmic reticulum	1
calcium ion import into sarcoplasmic reticulum	1

Protein interactions and networks

STRING

2294 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP2A1	SLN	O00631	991
ATP2A1	RYR1	P21817	928
ATP2A1	CLCN1	P35523	844
ATP2A1	MBNL1	Q9NR56	835
ATP2A1	SRL	Q86TD4	756
ATP2A1	PLN	P26678	752
ATP2A1	CASQ1	P31415	752
ATP2A1	DMPK	Q09013	740
ATP2A1	STIM1	Q13586	721
ATP2A1	TRDN	Q13061	701
ATP2A1	CELF1	Q92879	687
ATP2A1	FXYD2	P54710	680
ATP2A1	BCL2	P10415	657
ATP2A1	SIX5	Q8N196	640
ATP2A1	TNNT2	P45379	634

IntAct

68 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SETDB1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
MRAP2	PODXL	psi-mi:“MI:0914”(association)	0.530
NPTN	TNPO2	psi-mi:“MI:0914”(association)	0.530
ST6GAL1	ATP2A1	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
ATP2A1	CCR8	psi-mi:“MI:0915”(physical association)	0.370
JUN		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
COX15	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
DLST		psi-mi:“MI:0914”(association)	0.350
PDHA1		psi-mi:“MI:0914”(association)	0.350
COX15	SAP18	psi-mi:“MI:0914”(association)	0.350
METTL14	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
	TSPO	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
SH3BGRL	MYO1C	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (447): ATP2A1 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS)

ESM2 similar proteins: O14983, O22218, O23087, O46674, O55143, O77696, O81108, P04191, P07038, P09626, P11507, P11607, P13585, P16615, P18596, P19156, P20647, P20648, P22700, P27112, P35315, P35316, P50996, P54209, P70083, P92939, Q00779, Q03669, Q0VCY0, Q292Q0, Q2QY12, Q2RAS0, Q42883, Q4WND5, Q64436, Q64518, Q64578, Q7PPA5, Q8R429, Q8RUN1

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

4 interactions.

A	Effect	B	Mechanism
“MYOD1/SWI/SNF complex”	“up-regulates quantity by expression”	ATP2A1	“transcriptional regulation”
SLN	“down-regulates activity”	ATP2A1	binding
ANK1	“down-regulates activity”	ATP2A1	binding
ATP2A1	“down-regulates quantity”	calcium(2+)	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	76
Likely pathogenic	17
Uncertain significance	437
Likely benign	348
Benign	43

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1031711	NM_004320.6(ATP2A1):c.1672_1673dup (p.Leu559fs)	Pathogenic
1073847	NC_000016.9:g.(?28888809)(28916830_?)del	Pathogenic
1073848	NC_000016.9:g.(?28900098)(28900284_?)del	Pathogenic
1323768	NM_004320.6(ATP2A1):c.592del (p.Arg198fs)	Pathogenic
1323776	NM_004320.6(ATP2A1):c.706C>T (p.Arg236Ter)	Pathogenic
1323799	NM_004320.6(ATP2A1):c.2574C>G (p.Tyr858Ter)	Pathogenic
1330187	GRCh37/hg19 16p11.2(chr16:28784627-29230353)x1	Pathogenic
1335911	NM_004320.6(ATP2A1):c.178del (p.Leu60fs)	Pathogenic
1335913	NM_004320.6(ATP2A1):c.704T>A (p.Ile235Asn)	Pathogenic
1340944	GRCh37/hg19 16p11.2(chr16:28837905-29088624)x1	Pathogenic
1360311	NM_004320.6(ATP2A1):c.1966C>T (p.Arg656Ter)	Pathogenic
1412650	NM_004320.6(ATP2A1):c.2262C>G (p.Tyr754Ter)	Pathogenic
1414230	NM_004320.6(ATP2A1):c.2056_2057del (p.Lys686fs)	Pathogenic
1451853	NM_004320.6(ATP2A1):c.2615_2618del (p.His872fs)	Pathogenic
1451898	NM_004320.6(ATP2A1):c.888dup (p.Lys297Ter)	Pathogenic
148434	GRCh38/hg38 16p11.2(chr16:28850210-29032639)x1	Pathogenic
148525	GRCh38/hg38 16p11.2(chr16:28722418-29033455)x1	Pathogenic
149239	GRCh38/hg38 16p11.2(chr16:28813473-29032639)x1	Pathogenic
149412	GRCh38/hg38 16p11.2(chr16:28813473-29033455)x1	Pathogenic
149864	GRCh38/hg38 16p11.2(chr16:28832433-29019750)x1	Pathogenic
151536	GRCh38/hg38 16p11.2(chr16:28809422-29033455)x1	Pathogenic
153218	GRCh38/hg38 16p11.2(chr16:28696852-29039870)x1	Pathogenic
155233	GRCh38/hg38 16p11.2(chr16:28677764-29039870)x1	Pathogenic
155463	GRCh38/hg38 16p11.2(chr16:28807707-29039870)x1	Pathogenic
1679691	Single allele	Pathogenic
1703523	GRCh37/hg19 16p11.2(chr16:28689085-29051191)	Pathogenic
17802	NM_004320.6(ATP2A1):c.592C>T (p.Arg198Ter)	Pathogenic
17803	NM_004320.6(ATP2A1):c.2025C>A (p.Cys675Ter)	Pathogenic
17805	NM_004320.6(ATP2A1):c.440del (p.Pro147fs)	Pathogenic
1938875	NM_004320.6(ATP2A1):c.1912C>T (p.Arg638Ter)	Pathogenic

SpliceAI

2672 predictions. Top by Δscore:

Variant	Effect	Δscore
16:28878788:TGGTA:T	donor_loss	1.0000
16:28878790:GT:G	donor_loss	1.0000
16:28878791:TAAG:T	donor_loss	1.0000
16:28879497:CCAG:C	acceptor_loss	1.0000
16:28879499:A:C	acceptor_loss	1.0000
16:28879500:G:T	acceptor_loss	1.0000
16:28879500:GGGAA:G	acceptor_gain	1.0000
16:28879579:CCTTC:C	donor_gain	1.0000
16:28879580:CTTC:C	donor_gain	1.0000
16:28879581:TTC:T	donor_gain	1.0000
16:28879582:TC:T	donor_gain	1.0000
16:28879584:G:GG	donor_gain	1.0000
16:28881017:CAG:C	donor_loss	1.0000
16:28881018:AGGT:A	donor_loss	1.0000
16:28881019:GG:G	donor_loss	1.0000
16:28881020:G:T	donor_loss	1.0000
16:28881021:T:A	donor_loss	1.0000
16:28882436:ACCCT:A	acceptor_gain	1.0000
16:28882440:T:A	acceptor_gain	1.0000
16:28882447:TCA:T	acceptor_loss	1.0000
16:28882448:CAGG:C	acceptor_gain	1.0000
16:28882449:A:AC	acceptor_loss	1.0000
16:28882449:A:AG	acceptor_gain	1.0000
16:28882449:AG:A	acceptor_gain	1.0000
16:28882449:AGGA:A	acceptor_gain	1.0000
16:28882450:G:GT	acceptor_gain	1.0000
16:28882450:GG:G	acceptor_gain	1.0000
16:28882450:GGA:G	acceptor_gain	1.0000
16:28882450:GGAG:G	acceptor_gain	1.0000
16:28882450:GGAGC:G	acceptor_gain	1.0000

AlphaMissense

6481 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:28880967:C:A	P91H	1.000
16:28880967:C:G	P91R	1.000
16:28880988:T:A	L98H	1.000
16:28880988:T:C	L98P	1.000
16:28882478:G:C	A118P	1.000
16:28882482:T:C	L119P	1.000
16:28884655:G:C	G182R	1.000
16:28884655:G:T	G182C	1.000
16:28887189:G:A	G182D	1.000
16:28887189:G:T	G182V	1.000
16:28887444:G:A	G217D	1.000
16:28887573:T:C	L260P	1.000
16:28887596:T:C	C268R	1.000
16:28887597:G:A	C268Y	1.000
16:28887598:T:G	C268W	1.000
16:28887608:T:A	W272R	1.000
16:28887608:T:C	W272R	1.000
16:28887702:C:A	A303D	1.000
16:28887708:C:A	A305D	1.000
16:28887710:G:C	A306P	1.000
16:28887711:C:A	A306D	1.000
16:28887717:C:A	P308H	1.000
16:28887722:G:C	G310R	1.000
16:28888790:T:C	L311P	1.000
16:28888814:T:C	L319P	1.000
16:28888817:C:A	A320D	1.000
16:28888849:G:C	A331P	1.000
16:28888883:T:C	L342P	1.000
16:28888885:G:C	G343R	1.000
16:28888886:G:A	G343D	1.000

dbSNP variants (sampled 300 via entrez): RS1000013334 (16:28898999 A>C), RS1000122501 (16:28877464 A>G), RS1000279807 (16:28880763 G>A), RS1000284992 (16:28893348 A>G), RS1000444158 (16:28886680 G>C), RS1000481694 (16:28887797 CTTTTT>C,CT,CTTTT,CTTTTTT), RS1000500343 (16:28881357 C>T), RS1000533181 (16:28899946 C>T), RS1000899556 (16:28884509 G>A), RS1001044530 (16:28881725 T>TC), RS1001135745 (16:28887360 C>T), RS1001363572 (16:28892918 C>T), RS1001482647 (16:28904504 G>A), RS1001640287 (16:28899653 C>A,G,T), RS1001795995 (16:28892848 C>T)

Disease associations

OMIM: gene MIM:108730 | disease phenotypes: MIM:601003, MIM:611913, MIM:613444, MIM:606215

GenCC curated gene-disease

Disease	Classification	Inheritance
Brody myopathy	Strong	Autosomal recessive

Mondo (5): Brody myopathy (MONDO:0010977), proximal 16p11.2 microdeletion syndrome (MONDO:0012756), distal 16p11.2 microdeletion syndrome (MONDO:0013267), autism spectrum disorder (MONDO:0005258), familial atrioventricular septal defect (MONDO:0020290)

Orphanet (5): Brody myopathy (Orphanet:53347), Proximal 16p11.2 microdeletion syndrome (Orphanet:261197), Distal 16p11.2 microdeletion syndrome (Orphanet:261222), Atrioventricular septal defect (Orphanet:98722), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001270	Motor delay
HP:0001324	Muscle weakness
HP:0001371	Flexion contracture
HP:0002047	Malignant hyperthermia
HP:0002380	Fasciculations
HP:0002411	Myokymia
HP:0002486	Myotonia
HP:0003326	Myalgia
HP:0003474	Somatic sensory dysfunction
HP:0003623	Neonatal onset
HP:0003710	Exercise-induced muscle cramps
HP:0003712	Skeletal muscle hypertrophy
HP:0008967	Exercise-induced muscle stiffness
HP:0009046	Difficulty running
HP:0010548	Percussion myotonia
HP:0011463	Childhood onset
HP:0031826	Abnormal reflex
HP:0100284	EMG: myotonic discharges

GWAS associations

42 associations (top):

Study	Trait	p-value
GCST000296_2	Body mass index	3.000000e-10
GCST000299_2	Weight	1.000000e-09
GCST002783_112	Body mass index	4.000000e-12
GCST002783_126	Body mass index	3.000000e-23
GCST002783_356	Body mass index	3.000000e-25
GCST002783_595	Body mass index	1.000000e-17
GCST004066_127	Hip circumference	9.000000e-22
GCST004066_17	Hip circumference	3.000000e-14
GCST004066_49	Hip circumference	1.000000e-11
GCST004131_83	Inflammatory bowel disease	2.000000e-12
GCST004132_69	Crohn’s disease	3.000000e-10
GCST004364_11	Intelligence	4.000000e-08
GCST004364_31	Intelligence	1.000000e-08
GCST004495_1	BMI (adjusted for smoking behaviour)	6.000000e-11
GCST004495_144	BMI (adjusted for smoking behaviour)	6.000000e-10
GCST004495_145	BMI (adjusted for smoking behaviour)	2.000000e-18
GCST004497_73	Body mass index (joint analysis main effects and smoking interaction)	6.000000e-18
GCST004497_74	Body mass index (joint analysis main effects and smoking interaction)	2.000000e-11
GCST004497_75	Body mass index (joint analysis main effects and smoking interaction)	3.000000e-08
GCST004499_5	BMI in non-smokers	2.000000e-07
GCST004499_6	BMI in non-smokers	4.000000e-15
GCST004499_7	BMI in non-smokers	1.000000e-10
GCST004904_183	Body mass index	2.000000e-31
GCST005316_513	Intelligence (MTAG)	5.000000e-12
GCST006421_6	Cannabis use	1.000000e-09
GCST006802_29	Body mass index	8.000000e-09
GCST007044_23	Extremely high intelligence	2.000000e-08
GCST007293_116	Body fat distribution (arm fat ratio)	2.000000e-08
GCST007293_16	Body fat distribution (arm fat ratio)	4.000000e-09
GCST007293_43	Body fat distribution (arm fat ratio)	2.000000e-12

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004338	body weight
EFO:0004337	intelligence
EFO:0004318	smoking behavior
EFO:0007585	Cannabis use
EFO:0004341	body fat distribution
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C579850	16p11.2 Deletion Syndrome (supp.)
C536607	Brody myopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3136 (SINGLE PROTEIN), CHEMBL3831290 (PROTEIN FAMILY)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3888190	ATP2A1	3	2.25	1	amisulpride;aripiprazole;clozapine;lithium;mirtazapine;olanzapine;paliperidone;quetiapine;risperidone;valproic acid

GtoPdb / IUPHAR curated pharmacology

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

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

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
TGN4	Negative	8.92	pIC50
CDN1163	Activation	5.22	pEC50

ChEMBL bioactivities

8 potent at pChembl≥5 of 9 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	Ki	0.1	nM	THAPSIGARGIN
8.92	IC50	1.2	nM	CHEMBL365703
8.68	IC50	2.08	nM	CHEMBL191633
7.77	Ki	17	nM	CHEMBL4216774
7.72	Ki	19	nM	CHEMBL4207081
7.70	IC50	19.83	nM	CHEMBL191927
5.75	Ki	1800	nM	CYCLOPIAZONIC ACID
5.04	IC50	9038	nM	CHEMBL362947

PubChem BioAssay actives

8 with measured affinity, of 55 total; 8 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
[(3S,3aR,4S,6S,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	1370815: Inhibition of SERCA1a (unknown origin) ATPase activity	ki	0.0001	uM
5-[[12-[[(3S,3aR,4S,6S,6aR,7S,9bS)-6-acetyloxy-3,3a-dihydroxy-3,6,9-trimethyl-7-octanoyloxy-2,8-dioxo-5,6a,7,9b-tetrahydro-4H-azuleno[4,5-b]furan-4-yl]oxy]-12-oxododecyl]amino]-2-amino-5-oxopentanoic acid	241355: Inhibitory activity against sarco- endoplasmic reticulum calcium-ATPase	ic50	0.0012	uM
12-[[(3S,3aR,4S,6S,6aR,7S,9bS)-6-acetyloxy-3,3a-dihydroxy-3,6,9-trimethyl-7-octanoyloxy-2,8-dioxo-5,6a,7,9b-tetrahydro-4H-azuleno[4,5-b]furan-4-yl]oxy]-12-oxododecanoic acid	241355: Inhibitory activity against sarco- endoplasmic reticulum calcium-ATPase	ic50	0.0021	uM
(4S,5E,8S,9E,11S,13E,15E,18R)-4-hydroxy-8-methoxy-9,11-dimethyl-18-[(1Z,4E)-2-methylhexa-1,4-dienyl]-1-oxacyclooctadeca-5,9,13,15-tetraen-2-one	1370815: Inhibition of SERCA1a (unknown origin) ATPase activity	ki	0.0170	uM
(4S,5E,8S,9E,11S,13E,15E,18R)-4-[(2R,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-methoxyoxan-2-yl]oxy-8-methoxy-9,11-dimethyl-18-[(1Z,4E)-2-methylhexa-1,4-dienyl]-1-oxacyclooctadeca-5,9,13,15-tetraen-2-one	1370815: Inhibition of SERCA1a (unknown origin) ATPase activity	ki	0.0190	uM
5-[[(3S,3aR,4S,6S,6aR,7S,9bS)-6-acetyloxy-3,3a-dihydroxy-3,6,9-trimethyl-7-octanoyloxy-2,8-dioxo-5,6a,7,9b-tetrahydro-4H-azuleno[4,5-b]furan-4-yl]oxy]-5-oxopentanoic acid	241355: Inhibitory activity against sarco- endoplasmic reticulum calcium-ATPase	ic50	0.0198	uM
(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	1370815: Inhibition of SERCA1a (unknown origin) ATPase activity	ki	1.8000	uM
[(3S,3aR,4S,6S,6aR,7S,9bS)-6-acetyloxy-4-[4-(3-amino-4-methylanilino)-4-oxobutanoyl]oxy-3,3a-dihydroxy-3,6,9-trimethyl-2,8-dioxo-5,6a,7,9b-tetrahydro-4H-azuleno[4,5-b]furan-7-yl] octanoate	241355: Inhibitory activity against sarco- endoplasmic reticulum calcium-ATPase	ic50	9.0380	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression, decreases reaction	1
oxymatrine	decreases expression, decreases reaction	1
methacrylaldehyde	affects cotreatment, increases expression	1
monomethylarsonous acid	increases expression	1
jinfukang	decreases expression, affects cotreatment	1
theaflavin-3,3’-digallate	affects expression	1
Bortezomib	affects reaction, decreases expression, affects response to substance	1
Acrolein	affects cotreatment, increases expression	1
Aspirin	increases expression	1
Cisplatin	decreases expression, affects cotreatment	1
Diethylhexyl Phthalate	decreases expression	1
Furaldehyde	affects cotreatment, decreases expression	1
Ozone	increases expression, affects cotreatment	1
Quercetin	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Sodium Chloride	affects cotreatment, decreases expression, increases expression	1
Sulindac	decreases expression	1
Testosterone	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases expression, decreases methylation	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4184982	Binding	Inhibition of SERCA1a (unknown origin) ATPase activity	Design, synthesis and anti-malarial activities of synthetic analogs of biselyngbyolide B, a Ca2+ pump inhibitor from marine cyanobacteria. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder