ATP2B2

Summary

ATP2B2 (ATPase plasma membrane Ca2+ transporting 2, HGNC:815) is a protein-coding gene on chromosome 3p25.3, encoding Plasma membrane calcium-transporting ATPase 2 (Q01814). ATP-driven Ca(2+) ion pump involved in the maintenance of basal intracellular Ca(2+) levels in specialized cells of cerebellar circuit and vestibular and cochlear systems.

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 2. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 491 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant nonsyndromic hearing loss (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 632 total — 30 pathogenic, 21 likely-pathogenic
• Phenotypes (HPO): 7
• MANE Select transcript: NM_001001331

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:815
Approved symbol	ATP2B2
Name	ATPase plasma membrane Ca2+ transporting 2
Location	3p25.3
Locus type	gene with protein product
Status	Approved
Aliases	PMCA2
Ensembl gene	ENSG00000157087
Ensembl biotype	protein_coding
OMIM	108733
Entrez	491

Gene structure

Transcript identifiers

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

ENST00000352432, ENST00000360273, ENST00000397077, ENST00000452124, ENST00000460129, ENST00000467702, ENST00000468426, ENST00000480680, ENST00000638646, ENST00000643662, ENST00000644553, ENST00000644807, ENST00000645850, ENST00000646379

RefSeq mRNA: 5 — MANE Select: NM_001001331 NM_001001331, NM_001330611, NM_001353564, NM_001363862, NM_001683

CCDS: CCDS2601, CCDS33701, CCDS82733, CCDS87040

Canonical transcript exons

ENST00000360273 — 23 exons

Exon	Start	End
ENSE00003501657	10449345	10449862
ENSE00003556510	10324023	10329125
ENSE00003558162	10402091	10402348
ENSE00003602092	10410618	10410815
ENSE00003669676	10400953	10401078
ENSE00003850847	10505465	10505586
ENSE00003889108	10346031	10346137
ENSE00003889171	10371809	10372051
ENSE00003889807	10359882	10360123
ENSE00003890151	10345384	10345575
ENSE00003890596	10379243	10379284
ENSE00003891890	10375430	10375644
ENSE00003892527	10342752	10342965
ENSE00003892688	10386480	10386512
ENSE00003894175	10340493	10340704
ENSE00003894475	10358691	10358925
ENSE00003894488	10350112	10350199
ENSE00003894669	10338176	10338358
ENSE00003895107	10340242	10340349
ENSE00003895716	10388277	10388402
ENSE00003895726	10350398	10350577
ENSE00003895771	10385268	10385327
ENSE00003895857	10378252	10378410

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 99.53.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.8314 / max 174.6930, expressed in 150 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41054	4.3105	154
41067	0.9944	110
41065	0.7811	99
41055	0.7341	115
41057	0.1963	89
41066	0.0796	44
41052	0.0261	9
41056	0.0198	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	99.53	gold quality
endothelial cell	CL:0000115	98.91	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.86	gold quality
pons	UBERON:0000988	98.79	gold quality
middle temporal gyrus	UBERON:0002771	98.75	gold quality
lateral globus pallidus	UBERON:0002476	98.70	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.45	gold quality
parietal lobe	UBERON:0001872	98.41	gold quality
occipital lobe	UBERON:0002021	98.41	gold quality
postcentral gyrus	UBERON:0002581	98.27	gold quality
superior frontal gyrus	UBERON:0002661	98.26	gold quality
primary visual cortex	UBERON:0002436	98.24	gold quality
orbitofrontal cortex	UBERON:0004167	97.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.58	gold quality
cerebellar cortex	UBERON:0002129	97.55	gold quality
cerebellar hemisphere	UBERON:0002245	97.55	gold quality
cerebellum	UBERON:0002037	97.14	gold quality
entorhinal cortex	UBERON:0002728	96.65	gold quality
parotid gland	UBERON:0001831	96.58	gold quality
substantia nigra pars compacta	UBERON:0001965	96.41	gold quality
superior vestibular nucleus	UBERON:0007227	96.06	gold quality
prefrontal cortex	UBERON:0000451	95.99	gold quality
frontal cortex	UBERON:0001870	95.93	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.78	gold quality
right frontal lobe	UBERON:0002810	95.76	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.43	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.35	gold quality
neocortex	UBERON:0001950	94.80	gold quality
ventral tegmental area	UBERON:0002691	94.41	gold quality
cerebellar vermis	UBERON:0004720	94.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.37

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

299 targeting ATP2B2, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3925-3P	100.00	69.95	1237
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-MIR-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
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-196A-1-3P	99.99	72.15	2772
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4789-3P	99.99	70.75	2484

Literature-anchored findings (GeneRIF, showing 28)

• Alternative splicing of the first intracellular loop of PMCA2 alters its membrane targeting (PMID:12624087)
• 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)
• Decrease in PMCA2 transcript and protein levels and correlation between expression and disease course in two different allergic encephalomyelitis models further highlight the importance of this calcium pump in neuronal dysfunction during inflammation. (PMID:15926914)
• We conclude that PMCA2 mRNA can be highly overexpressed in some breast cancer cells. (PMID:16216224)
• plasma-membrane calcium-pump isoform 2 mutants have roles in causing digenic deafness (PMID:17234811)
• Our results indicate that a loss of PMCA such as occurs in aging brain likely leads to subtle disruptions in normal Ca(2+) signaling and enhanced susceptibility to stresses that can alter the regulation of Ca(2+) homeostasis. (PMID:17488275)
• The deaf-waddler isoform of PMCA2, operating at 30% efficacy, showed a significantly decreased ability to rescue the Ca(2+) loading of cells expressing TRPML3(A419P). (PMID:19299509)
• These data indicate that alternative splicing differentially affects the lipid interactions of PMCA2w/b and PMCA2z/b and that the apical localization of PMCA2w/b is lipid raft-dependent and sensitive to cholesterol depletion. (PMID:19379709)
• Report a novel interaction between endogenous plasma membrane calcium ATPase (PMCA) and eNOS in endothelial cells. PMCA may negatively modulate eNOS activity, and NO-dependent signal transduction pathways. (PMID:20211863)
• Apical scaffolding protein NHERF2 modulates the localization of alternatively spliced plasma membrane Ca2+ pump 2B variants in polarized epithelial cells. (PMID:20663896)
• It appears that Ca extrusion via the sarcolemmal Ca ATPase occurs only at the t-tubules, and is not regulated by basal PKA activity. (PMID:20971118)
• these data suggest that full polarization is a prerequisite for proper positioning of the PMCA2w variants in the apical membrane domain of polarized cells. (PMID:21672522)
• These results provide converging evidence for an association between ATP2B2 gene variants and autism in male subjects (PMID:21757185)
• The human mutant of PMCA2 exacerbated the deafness produced by a cadherin 23 mutation. The human mutant failed to impair the Ca(2+) ejection by the pump. (PMID:22047666)
• G293S and V586M mutations in the PMCA2 Calcium Transporting ATPase of the stereocilia are associated with deafness. (Review) (PMID:22349217)
• ATP2B2 might play a role in the etiology of autism in Chinese Han population. (PMID:23620727)
• SERCA and PMCA pump activities are strongly affected by the localization of F508del-CFTR protein. (PMID:25661196)
• PMCA2b resulted in rapid and highly PMCA abundance-sensitive clearance of store-operated Ca2+ entry-mediated Ca2+ transients. (PMID:25690014)
• PMCA2 interacts with HER2 in specific actin-rich membrane domains. (PMID:26729871)
• PMCA2 regulates breast cancer cell proliferation and sensitivity to doxorubicin in basal cell carcinoma. (PMID:27148852)
• Data show that ATPase, calcium transporting, plasma membrane 2 protein (PMCA2) silencing augmented B-cell leukemia 2 family proteins (Bcl-2) inhibitor ABT-263-mediated MDA-MB-231 breast cancer cell death. (PMID:27613092)
• NHERF1 acts with PMCA2 to regulate HER2 signaling and membrane retention in breast cancers (PMID:28235801)
• Cytoskeleton dynamics regulates plasma membrane PMCA2 activity. (PMID:28527708)
• critical role played by the PMCA2w/a pump in the control of hair cell function and survival, and provide mechanistic insight into the etiology of deafness and vestibular disorders. (PMID:29452611)
• PMCA2 loss plays a role in the ataxic phenotype, but can paradoxically also minimise calcium rises in cerebellar Purkinje neurons, thereby ensuring their resilience and survival. (PMID:29452612)
• A V1143F substitution in PMAC2 alters the binding of caslmodulin to the calmodulin-binding domain leading to impaired calcium signaling. (PMID:29655659)
• Loss-of-function variants of ATP2B2 are associated with rapidly progressive hearing impairment. (PMID:30535804)
• ATP2B2 de novo variants as a cause of variable neurodevelopmental disorders that feature dystonia, ataxia, intellectual disability, behavioral symptoms, and seizures. (PMID:37675773)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-28b4.8	ENSDARG00000002840
danio_rerio	atp1a3a	ENSDARG00000018259
danio_rerio	atp2b2	ENSDARG00000063433
danio_rerio	atp1a3b	ENSDARG00000104139
mus_musculus	Atp2b2	ENSMUSG00000030302
rattus_norvegicus	Atp2b2	ENSRNOG00000030269
drosophila_melanogaster	anne	FBGN0052000
drosophila_melanogaster	SPoCk	FBGN0052451
drosophila_melanogaster	CG45062	FBGN0266432
drosophila_melanogaster	CG45063	FBGN0266433
caenorhabditis_elegans		WBGENE00000834
caenorhabditis_elegans		WBGENE00003153
caenorhabditis_elegans	pmr-1	WBGENE00004063
caenorhabditis_elegans		WBGENE00012341
caenorhabditis_elegans		WBGENE00015338
caenorhabditis_elegans		WBGENE00015660
caenorhabditis_elegans		WBGENE00019875

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), ATP13A2 (ENSG00000159363), ATP1A1 (ENSG00000163399), ATP7A (ENSG00000165240), ATP2A2 (ENSG00000174437), ATP13A5 (ENSG00000187527), ATP2A1 (ENSG00000196296)

Protein

Protein identifiers

Plasma membrane calcium-transporting ATPase 2 — Q01814 (reviewed: Q01814)

Alternative names: Plasma membrane calcium ATPase isoform 2, Plasma membrane calcium pump isoform 2

All UniProt accessions (5): Q01814, A0A2R8Y4R4, A0A2R8Y535, A0A2U3TZI3, A0A2U3U055

UniProt curated annotations — full annotation on UniProt →

Function. ATP-driven Ca(2+) ion pump involved in the maintenance of basal intracellular Ca(2+) levels in specialized cells of cerebellar circuit and vestibular and cochlear systems. Uses ATP as an energy source to transport cytosolic Ca(2+) ions across the plasma membrane to the extracellular compartment. Has fast activation and Ca(2+) clearance rate suited to control fast neuronal Ca(2+) dynamics. At parallel fiber to Purkinje neuron synapse, mediates presynaptic Ca(2+) efflux in response to climbing fiber-induced Ca(2+) rise. Provides for fast return of Ca(2+) concentrations back to their resting levels, ultimately contributing to long-term depression induction and motor learning. Plays an essential role in hearing and balance. In cochlear hair cells, shuttles Ca(2+) ions from stereocilia to the endolymph and dissipates Ca(2+) transients generated by the opening of the mechanoelectrical transduction channels. Regulates Ca(2+) levels in the vestibular system, where it contributes to the formation of otoconia. In non-excitable cells, regulates Ca(2+) signaling through spatial control of Ca(2+) ions extrusion and dissipation of Ca(2+) transients generated by store-operated channels. In lactating mammary gland, allows for the high content of Ca(2+) ions in the milk.

Subunit / interactions. Interacts with PDZD11.

Subcellular location. Cell membrane. Synapse Apical cell membrane. Basolateral cell membrane Apical cell membrane. Basolateral cell membrane Basolateral cell membrane Basolateral cell membrane Basolateral cell membrane.

Tissue specificity. Mainly expressed in brain cortex. Found in low levels in skeletal muscle, heart muscle, stomach, liver, kidney and lung. Isoforms containing segment B are found in brain cortex and at low levels in other tissues. Isoforms containing segments X and W are found at low levels in all tissues. Isoforms containing segment A and segment Z are found at low levels in skeletal muscle and heart muscle.

Disease relevance. May act as a disease modifier. ATP2B2 variants may exacerbate the severity of non-syndromic sensorineural hearing loss in patients carrying causative variants in the CDH23 gene. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. Deafness, autosomal dominant, 82 (DFNA82) [MIM:619804] A form of non-syndromic, sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DNFA82 is characterized by onset of rapidly progressive bilateral sensorineural hearing loss usually early in the first decade. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Up-regulated by calmodulin which increases the affinity of the pump for Ca(2+) ions.

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

Isoforms (8)

UniProt ID	Names	Canonical?
Q01814-1	WB, AIIICI	yes
Q01814-2	WA, AIIICII
Q01814-3	YA, AIICII
Q01814-4	ZA, AICII
Q01814-5	YB, AIICI
Q01814-6	ZB, AICI
Q01814-7	XA
Q01814-8	XB

RefSeq proteins (5): NP_001001331, NP_001317540, NP_001340493, NP_001350791, NP_001674 (=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 (61 total): modified residue 14, topological domain 11, transmembrane region 10, region of interest 5, sequence variant 5, sequence conflict 5, splice variant 4, compositionally biased region 3, binding site 2, chain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01814-F1	73.83	0.20

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): 499 (4-aspartylphosphate intermediate)

Ligand- & substrate-binding residues (2): 820; 824

Post-translational modifications (14): 18, 1139, 1178, 1188, 1201, 1211, 1165, 1177, 1151, 1163, 1120, 1132, 1134, 1146

Function

Pathways and Gene Ontology

Reactome pathways

12 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-9662361	Sensory processing of sound by outer 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-983712	Ion channel transport

MSigDB gene sets: 308 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_CIRCULATORY_SYSTEM_PROCESS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, TTCCGTT_MIR191, CMYB_01, AAGCCAT_MIR135A_MIR135B, GOBP_NEUROGENESIS, MORF_RAD51L3, SREBP1_02, GOBP_MONOATOMIC_CATION_TRANSPORT, MODULE_66, CATRRAGC_UNKNOWN, JAZAG_TGFB1_SIGNALING_DN, CATTTCA_MIR203

GO Biological Process (9): calcium ion transport (GO:0006816), sensory perception of sound (GO:0007605), neuron differentiation (GO:0030182), monoatomic ion transmembrane transport (GO:0034220), regulation of cytosolic calcium ion concentration (GO:0051480), regulation of cardiac conduction (GO:1903779), monoatomic ion transport (GO:0006811), calcium ion transmembrane transport (GO:0070588), regulation of postsynaptic cytosolic calcium ion concentration (GO:0099566)

GO Molecular Function (11): P-type calcium transporter activity (GO:0005388), calcium ion binding (GO:0005509), calmodulin binding (GO:0005516), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), PDZ domain binding (GO:0030165), metal ion binding (GO:0046872), P-type calcium transporter activity involved in regulation of postsynaptic cytosolic calcium ion concentration (GO:1905059), nucleotide binding (GO:0000166), transporter activity (GO:0005215), protein binding (GO:0005515)

GO Cellular Component (11): cytoplasm (GO:0005737), plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), dendritic spine membrane (GO:0032591), extracellular exosome (GO:0070062), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), membrane (GO:0016020), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Sensory processing of sound	2
Platelet calcium homeostasis	1
Cardiac conduction	1
Ion channel transport	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
cellular anatomical structure	2
plasma membrane region	2
synapse	2
metal ion transport	1
sensory perception of mechanical stimulus	1
cell differentiation	1
generation of neurons	1
monoatomic ion transport	1
transmembrane transport	1
intracellular calcium ion homeostasis	1
regulation of heart contraction	1
cardiac conduction	1
transport	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
regulation of cytosolic calcium ion concentration	1
postsynapse	1
calcium ion transmembrane transporter activity	1
P-type ion transporter activity	1
ATPase-coupled monoatomic cation transmembrane transporter activity	1
metal ion binding	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
protein domain specific binding	1
cation binding	1
P-type calcium transporter activity	1
regulation of postsynaptic cytosolic calcium ion concentration	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
basal plasma membrane	1
apical part of cell	1
neuron projection membrane	1

Protein interactions and networks

STRING

3524 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP2B2	CDH23	Q9H251	897
ATP2B2	CALM1	P02593	895
ATP2B2	CALML3	P27482	892
ATP2B2	CALML5	Q9NZT1	892
ATP2B2	CALML6	Q8TD86	887
ATP2B2	CALML4	Q96GE6	887
ATP2B2	PCDH15	Q96QU1	800
ATP2B2	OC90	Q02509	789
ATP2B2	OTOP1	Q7RTM1	759
ATP2B2	NHERF1	O14745	728
ATP2B2	NHERF2	Q15599	697
ATP2B2	MYO7A	P78427	689
ATP2B2	SLC8A1	P32418	671
ATP2B2	ITPR1	Q14643	670
ATP2B2	E9PNW1	E9PNW1	667

IntAct

113 interactions, top by confidence:

A	B	Type	Score
RXYLT1	FKTN	psi-mi:“MI:0914”(association)	0.710
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
EIF2B2	SLC27A2	psi-mi:“MI:0914”(association)	0.640
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
LPAR4	POTEF	psi-mi:“MI:0914”(association)	0.530
SLC2A5	RBFOX3	psi-mi:“MI:0914”(association)	0.530
VSIG4	TCAF2	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
EFNB2	FAM171A2	psi-mi:“MI:0914”(association)	0.530
NUFIP1	PDE2A	psi-mi:“MI:0914”(association)	0.530
SPRING1	PLSCR1	psi-mi:“MI:0914”(association)	0.530
GALNT6	NDUFS4	psi-mi:“MI:0914”(association)	0.530
GPR161	USP12	psi-mi:“MI:0914”(association)	0.530
PTGIR	TMEM63A	psi-mi:“MI:0914”(association)	0.530
SLC22A16	APBA3	psi-mi:“MI:0914”(association)	0.530
ENTPD7	PGK2	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CCR6	PODXL	psi-mi:“MI:0914”(association)	0.530
NPTN	TNPO2	psi-mi:“MI:0914”(association)	0.530
CALCA	ATP2B4	psi-mi:“MI:0914”(association)	0.500
ATP2B2	CALCA	psi-mi:“MI:0915”(physical association)	0.500
SCRIB	ATP2B2	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRQ	NHERF1	psi-mi:“MI:0914”(association)	0.350
	TSPO	psi-mi:“MI:0914”(association)	0.350
CD81	PVR	psi-mi:“MI:0914”(association)	0.350
SST	ATP1A2	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
ATP2B2	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (295): ATP2B2 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B2 (Affinity Capture-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: A3FIN4, B1AWN4, C7EXK4, D4AA47, G0S196, G2X7W6, O43520, O54827, O60312, O94296, O94823, P11506, P32660, P39524, P54678, P57792, P70704, P98196, P98197, P98198, P98199, P98200, P98204, Q01814, Q09891, Q12675, Q148W0, Q29449, Q5BL50, Q6DFW5, Q6UQ17, Q8K2X1, Q8TF62, Q9GKS6, Q9LI83, Q9LK90, Q9LNQ4, Q9LVK9, Q9N0Z4, Q9NTI2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ATP8B1	up-regulates	ATP2B2
ATP2B2	“down-regulates quantity”	calcium(2+)	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 168 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
Ion transport by P-type ATPases	6	10.9×	3e-03
Class A/1 (Rhodopsin-like receptors)	10	6.5×	2e-03
G alpha (s) signalling events	9	5.8×	3e-03
GPCR ligand binding	10	5.6×	3e-03
Signaling by GPCR	12	4.2×	3e-03
GPCR downstream signalling	11	4.2×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of cytosolic calcium ion concentration	5	12.9×	6e-03
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	6	8.9×	8e-03
positive regulation of cytosolic calcium ion concentration	11	8.7×	7e-05
phospholipase C-activating G protein-coupled receptor signaling pathway	9	8.0×	6e-04
adenylate cyclase-activating G protein-coupled receptor signaling pathway	10	7.6×	3e-04
G protein-coupled receptor signaling pathway	18	4.4×	8e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	30
Likely pathogenic	21
Uncertain significance	290
Likely benign	165
Benign	98

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1360768	NM_001001331.4(ATP2B2):c.3058dup (p.Arg1020fs)	Pathogenic
1400721	NM_001001331.4(ATP2B2):c.1713C>A (p.Cys571Ter)	Pathogenic
148687	GRCh38/hg38 3p25.3(chr3:9875909-10572677)x1	Pathogenic
148942	GRCh38/hg38 3p26.3-24.1(chr3:32241-30064208)x3	Pathogenic
1525986	NM_001001331.4(ATP2B2):c.955del (p.Ala319fs)	Pathogenic
1525987	NM_001001331.4(ATP2B2):c.2329C>T (p.Arg777Ter)	Pathogenic
1525988	NM_001001331.4(ATP2B2):c.1963G>T (p.Glu655Ter)	Pathogenic
1525989	NM_001001331.4(ATP2B2):c.1998C>A (p.Cys666Ter)	Pathogenic
1699521	NM_001001331.4(ATP2B2):c.2461G>A (p.Gly821Arg)	Pathogenic
1997758	NM_001001331.4(ATP2B2):c.532C>T (p.Gln178Ter)	Pathogenic
2006763	NM_001001331.4(ATP2B2):c.2920G>T (p.Glu974Ter)	Pathogenic
2018216	NM_001001331.4(ATP2B2):c.2726_2729dup (p.Met910fs)	Pathogenic
2080750	NM_001001331.4(ATP2B2):c.1924dup (p.Ala642fs)	Pathogenic
2424613	NC_000003.11:g.(?10094051)(11078652_?)del	Pathogenic
2816938	NM_001001331.4(ATP2B2):c.1989del (p.Met664fs)	Pathogenic
2836858	NM_001001331.4(ATP2B2):c.1123A>T (p.Lys375Ter)	Pathogenic
2844808	NM_001001331.4(ATP2B2):c.178del (p.Leu60fs)	Pathogenic
2976958	NM_001001331.4(ATP2B2):c.896_899del (p.Lys299fs)	Pathogenic
3067646	NM_001001331.4(ATP2B2):c.2515del (p.Ile839fs)	Pathogenic
3336824	NM_001001331.4(ATP2B2):c.3259del (p.Ser1087fs)	Pathogenic
3366952	NM_001001331.4(ATP2B2):c.1043-2A>G	Pathogenic
3661593	NM_001001331.4(ATP2B2):c.2492C>T (p.Ala831Val)	Pathogenic
3722000	NM_001001331.4(ATP2B2):c.1761dup (p.Arg588fs)	Pathogenic
3728302	NM_001001331.4(ATP2B2):c.1503del (p.Gly502fs)	Pathogenic
4690272	NM_001001331.4(ATP2B2):c.358G>A (p.Gly120Arg)	Pathogenic
4714251	NM_001001331.4(ATP2B2):c.2870del (p.Gly957fs)	Pathogenic
4724146	NM_001001331.4(ATP2B2):c.2261_2264del (p.Phe754fs)	Pathogenic
4730226	NM_001001331.4(ATP2B2):c.272del (p.Lys91fs)	Pathogenic
4822875	NM_001001331.4(ATP2B2):c.2152del (p.Arg718fs)	Pathogenic
917514	NM_001001331.4(ATP2B2):c.1033C>T (p.Gln345Ter)	Pathogenic

SpliceAI

4103 predictions. Top by Δscore:

Variant	Effect	Δscore
3:10329121:CGGAT:C	acceptor_gain	1.0000
3:10329123:GATCT:G	acceptor_loss	1.0000
3:10329126:C:CC	acceptor_gain	1.0000
3:10329127:T:G	acceptor_loss	1.0000
3:10336215:T:TA	donor_gain	1.0000
3:10338171:TGTAC:T	donor_loss	1.0000
3:10338172:GTAC:G	donor_loss	1.0000
3:10338173:TA:T	donor_loss	1.0000
3:10338175:C:CG	donor_loss	1.0000
3:10338357:ACC:A	acceptor_loss	1.0000
3:10338359:C:CC	acceptor_gain	1.0000
3:10338359:C:T	acceptor_loss	1.0000
3:10338360:T:A	acceptor_loss	1.0000
3:10340346:CTAT:C	acceptor_gain	1.0000
3:10340360:C:CT	acceptor_gain	1.0000
3:10340361:A:T	acceptor_gain	1.0000
3:10340368:C:CT	acceptor_gain	1.0000
3:10340369:A:T	acceptor_gain	1.0000
3:10340489:CTA:C	donor_gain	1.0000
3:10340490:TAC:T	donor_loss	1.0000
3:10340492:C:CA	donor_loss	1.0000
3:10340700:CTCGC:C	acceptor_gain	1.0000
3:10340702:CGC:C	acceptor_gain	1.0000
3:10340703:GC:G	acceptor_gain	1.0000
3:10340704:CC:C	acceptor_gain	1.0000
3:10340705:C:CC	acceptor_gain	1.0000
3:10340705:CTG:C	acceptor_loss	1.0000
3:10340709:C:CT	acceptor_gain	1.0000
3:10342746:GCTCA:G	donor_loss	1.0000
3:10342747:CTCA:C	donor_loss	1.0000

AlphaMissense

8226 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:10329105:G:C	F1147L	1.000
3:10329105:G:T	F1147L	1.000
3:10329107:A:G	F1147L	1.000
3:10338186:A:T	I1137N	1.000
3:10338189:C:G	R1136P	1.000
3:10338208:A:G	W1130R	1.000
3:10338208:A:T	W1130R	1.000
3:10340250:A:G	W1077R	1.000
3:10340250:A:T	W1077R	1.000
3:10340289:A:G	W1064R	1.000
3:10340289:A:T	W1064R	1.000
3:10340311:G:C	C1056W	1.000
3:10340581:C:G	R1014P	1.000
3:10340582:G:T	R1014S	1.000
3:10340625:G:C	F999L	1.000
3:10340625:G:T	F999L	1.000
3:10340627:A:G	F999L	1.000
3:10342832:A:T	L946H	1.000
3:10342859:C:A	R937M	1.000
3:10342892:G:T	A926D	1.000
3:10342895:A:G	L925P	1.000
3:10342895:A:T	L925Q	1.000
3:10342901:A:G	L923P	1.000
3:10342907:G:T	A921D	1.000
3:10342915:G:C	D918E	1.000
3:10342915:G:T	D918E	1.000
3:10342916:T:A	D918V	1.000
3:10342916:T:C	D918G	1.000
3:10342916:T:G	D918A	1.000
3:10342917:C:G	D918H	1.000

dbSNP variants (sampled 300 via entrez): RS1000003964 (3:10608361 C>A), RS1000007150 (3:10457920 C>G,T), RS1000012612 (3:10385770 C>A), RS1000017550 (3:10656472 C>A,T), RS1000019117 (3:10491412 G>A), RS1000022263 (3:10451165 G>T), RS1000027214 (3:10644926 T>C), RS1000032727 (3:10604934 C>T), RS1000043229 (3:10418104 G>A,C), RS1000046425 (3:10611047 C>T), RS1000053378 (3:10383099 T>C,G), RS1000062082 (3:10374649 G>A), RS1000078556 (3:10610783 C>T), RS1000087894 (3:10336088 G>A), RS1000088384 (3:10460251 C>T)

Disease associations

OMIM: gene MIM:108733 | disease phenotypes: MIM:619804, MIM:218000, MIM:616421, MIM:601386, MIM:124900

GenCC curated gene-disease

Disease	Classification	Inheritance
hearing loss, autosomal dominant 82	Definitive	Autosomal dominant
autosomal dominant nonsyndromic hearing loss	Definitive	Autosomal dominant
neurodevelopmental disorder	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
autosomal dominant nonsyndromic hearing loss	Definitive	AD

Mondo (8): hearing loss disorder (MONDO:0005365), neurodevelopmental disorder (MONDO:0700092), hearing loss, autosomal dominant 82 (MONDO:0030719), agenesis of the corpus callosum with peripheral neuropathy (MONDO:0000902), epilepsy with myoclonic atonic seizures (MONDO:0014633), autosomal recessive nonsyndromic hearing loss 12 (MONDO:0011067), intellectual disability (MONDO:0001071), autosomal dominant nonsyndromic hearing loss (MONDO:0019587)

Orphanet (5): Corpus callosum agenesis-neuronopathy syndrome (Orphanet:1496), Epilepsy with myoclonic-atonic seizures (Orphanet:1942), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000360	Tinnitus
HP:0000407	Sensorineural hearing impairment
HP:0003577	Congenital onset
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0011463	Childhood onset

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000274_8	Metabolite levels	1.000000e-07
GCST002337_149	Amyotrophic lateral sclerosis (sporadic)	7.000000e-06
GCST002932_14	Manganese levels	7.000000e-06
GCST003075_81	Cognitive decline rate in late mild cognitive impairment	5.000000e-07
GCST004521_106	Autism spectrum disorder or schizophrenia	2.000000e-08
GCST008103_75	Bipolar disorder	9.000000e-07
GCST012490_371	Femur bone mineral density x serum urate levels interaction	3.000000e-08
GCST90020028_769	Hip circumference adjusted for BMI	7.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005001	phenylalanine measurement
EFO:0007710	cognitive decline measurement
EFO:0004531	urate measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C536446	Corpus callosum agenesis neuronopathy (supp.)
C563327	Deafness, Autosomal Recessive 12 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Valproic Acid	affects expression, increases methylation	2
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	2
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
methyleugenol	decreases expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
ethyl-p-hydroxybenzoate	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	decreases expression, increases methylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
perfluoro-n-nonanoic acid	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Sunitinib	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Carbamazepine	affects expression	1
Methapyrilene	increases methylation	1
Triclosan	decreases expression	1
Urethane	decreases expression	1
Vanadium	increases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Uranium Compounds	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E9XZ	HEK293-ATP2B2-RFP	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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,
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
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
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
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
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
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
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC