ATP2B2

ATPase plasma membrane Ca2+ transporting 2, the group of ATPases Ca2+ transporting|MicroRNA protein coding host genes

Basic information

Region (hg38): 3:10324023-10708007

Links

ENSG00000157087 ∙ NCBI:491 ∙ OMIM:108733 ∙ HGNC:815 ∙ Uniprot:Q01814 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 12 (Strong), mode of inheritance: AD
• hearing loss, autosomal dominant 82 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 82	AD	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	30535804

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATP2B2 gene.

• not provided (12 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP2B2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	71	25	99
missense	1	1	130	8	2	142
nonsense	4	1				5
start loss			1			1
frameshift	7	2	1			10
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)		4		1		5
splice region			8	8	2	18
non coding			2	13	65	80
Total	12	9	138	93	92

Variants in ATP2B2

This is a list of pathogenic ClinVar variants found in the ATP2B2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-10328802-G-C			Benign (May 10, 2021)
3-10328812-A-G		ATP2B2-related disorder	Likely benign (Aug 10, 2020)
3-10328823-C-T		ATP2B2-related disorder	Likely benign (Apr 01, 2023)
3-10328838-G-T			Likely benign (Sep 27, 2022)
3-10328892-G-A			Likely benign (Mar 01, 2023)
3-10328907-G-A		ATP2B2-related disorder	Likely benign (Apr 30, 2019)
3-10328937-C-T			Likely benign (Sep 08, 2023)
3-10328940-C-T			Likely benign (Nov 07, 2023)
3-10328947-G-A			Uncertain significance (May 09, 2023)
3-10328961-C-T			Likely benign (Apr 20, 2023)
3-10328962-G-A			Uncertain significance (Jan 15, 2023)
3-10328963-C-T			Likely benign (Nov 10, 2023)
3-10328964-G-A			Likely benign (Oct 19, 2023)
3-10328983-G-C			Uncertain significance (Nov 22, 2022)
3-10329025-C-T			Uncertain significance (Jan 21, 2022)
3-10329074-G-C		not specified	Uncertain significance (Aug 28, 2023)
3-10329089-CAT-C			Uncertain significance (Jul 21, 2022)
3-10329108-C-T			Likely benign (Nov 22, 2022)
3-10329116-C-T		Hearing loss, autosomal dominant 82	Likely pathogenic (Apr 18, 2024)
3-10329121-C-T		not specified	Uncertain significance (Mar 07, 2024)
3-10331823-A-G			Benign (May 24, 2021)
3-10335966-C-T			Benign (May 10, 2021)
3-10336128-C-T		ATP2B2-related disorder	Uncertain significance (Dec 27, 2023)
3-10336131-C-G			Uncertain significance (Feb 01, 2024)
3-10336178-C-A			Uncertain significance (Mar 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATP2B2	protein_coding	protein_coding	ENST00000360273	22	384010

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	7.49e-7	125728	0	20	125748	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.55	431	791	0.545	0.0000554	8189
Missense in Polyphen		216	466.62	0.46291		4759
Synonymous	-0.802	366	347	1.05	0.0000282	2469
Loss of Function	6.33	3	52.5	0.0572	0.00000254	614

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000158	0.000158
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.
• Pathway: Aldosterone synthesis and secretion - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Calcium Regulation in the Cardiac Cell;Ion channel transport;Purine metabolism;Ion homeostasis;Transport of small molecules;Cardiac conduction;Muscle contraction;Ion transport by P-type ATPases;Hemostasis;Reduction of cytosolic Ca++ levels;Platelet calcium homeostasis;Platelet homeostasis (Consensus)

Recessive Scores

• pRec: 0.180

Intolerance Scores

• loftool: 0.00400
• rvis_EVS: -1.94
• rvis_percentile_EVS: 1.89

Haploinsufficiency Scores

• pHI: 0.699
• hipred: Y
• hipred_score: 0.736
• ghis: 0.692

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.744

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Atp2b2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype; cellular phenotype

Gene ontology

• Biological process: calcium ion transport;cellular calcium ion homeostasis;sensory perception of sound;neuron differentiation;ion transmembrane transport;regulation of cytosolic calcium ion concentration;calcium ion transmembrane transport;ATP hydrolysis coupled cation transmembrane transport;regulation of presynaptic cytosolic calcium ion concentration;regulation of postsynaptic cytosolic calcium ion concentration;regulation of cardiac conduction
• Cellular component: cytoplasm;plasma membrane;integral component of plasma membrane;cell junction;extracellular exosome;presynapse;postsynaptic density membrane;glutamatergic synapse;GABA-ergic synapse
• Molecular function: calcium-transporting ATPase activity;protein binding;calmodulin binding;ATP binding;PDZ domain binding;metal ion binding;calcium-transporting ATPase activity involved in regulation of presynaptic cytosolic calcium ion concentration;calcium-transporting ATPase activity involved in regulation of postsynaptic cytosolic calcium ion concentration