ATP2B1

ATPase plasma membrane Ca2+ transporting 1, the group of ATPases Ca2+ transporting

Basic information

Region (hg38): 12:89588049-89709366

Links

ENSG00000070961 ∙ NCBI:490 ∙ OMIM:108731 ∙ HGNC:814 ∙ Uniprot:P20020 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder, autosomal dominant 66 (Moderate), mode of inheritance: AD
• intellectual developmental disorder, autosomal dominant 66 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 66	AD	General	Among other findings, the condition can involve congenital heart anomalies, and awareness may allow prompt diagnosis and management	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic	35358416

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATP2B1 gene.

• not provided (3 variants)
• Intellectual developmental disorder, autosomal dominant 66 (1 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP2B1 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			1	2	4	7
missense	1	8	54			63
nonsense	2	4	2			8
start loss						0
frameshift	1	2	1			4
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)		2				2
splice region			1			1
non coding						0
Total	4	17	59	2	4

Highest pathogenic variant AF is 0.00000661

Variants in ATP2B1

This is a list of pathogenic ClinVar variants found in the ATP2B1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-89591006-T-C		Inborn genetic diseases	Uncertain significance (May 08, 2024)
12-89591012-G-A			Uncertain significance (Nov 01, 2023)
12-89591015-C-A		Intellectual developmental disorder, autosomal dominant 66	Uncertain significance (Aug 01, 2022)
12-89591050-T-G		Inborn genetic diseases	Uncertain significance (Mar 30, 2024)
12-89591054-A-G		Inborn genetic diseases	Uncertain significance (Mar 30, 2024)
12-89591090-T-C			Uncertain significance (Nov 28, 2022)
12-89591097-T-C		Inborn genetic diseases	Uncertain significance (May 15, 2023)
12-89591105-G-T		Inborn genetic diseases	Likely benign (Jun 14, 2024)
12-89591106-G-T		Inborn genetic diseases	Uncertain significance (Sep 14, 2021)
12-89591108-G-T		Inborn genetic diseases	Uncertain significance (Jul 06, 2021)
12-89591192-A-G		not specified	Uncertain significance (Mar 08, 2024)
12-89591194-C-G			Uncertain significance (Aug 16, 2022)
12-89591227-C-A			Benign (Aug 16, 2018)
12-89591280-C-A		Intellectual developmental disorder, autosomal dominant 66	Uncertain significance (Feb 23, 2023)
12-89599230-C-T		Inborn genetic diseases	Uncertain significance (Apr 12, 2022)
12-89601384-G-C		Neurodevelopmental disorder	Likely pathogenic (Aug 29, 2022)
12-89603041-A-C		Hypocalcemia;Neurodevelopmental delay;Clubfoot;Isolated Pierre-Robin syndrome;Periventricular nodular heterotopia	Likely pathogenic (Jan 12, 2022)
12-89603048-C-G		not specified	Uncertain significance (Aug 25, 2023)
12-89603068-A-G		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
12-89603103-G-T		Inborn genetic diseases	Uncertain significance (Aug 16, 2021)
12-89603131-C-T		Neurodevelopmental disorder	Likely pathogenic (Apr 11, 2022)
12-89603144-C-A		Intellectual disability, autosomal dominant 30	Likely pathogenic (-)
12-89603165-C-A		Hypocalcemia;Neurodevelopmental delay;Clubfoot;Isolated Pierre-Robin syndrome;Periventricular nodular heterotopia	Likely pathogenic (Jan 12, 2022)
12-89603191-T-C			Uncertain significance (Mar 09, 2024)
12-89603210-G-C		Inborn genetic diseases	Uncertain significance (Dec 29, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATP2B1	protein_coding	protein_coding	ENST00000428670	20	121250

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.69e-9	125731	0	6	125737	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.29	271	651	0.416	0.0000332	7990
Missense in Polyphen		86	309.61	0.27777		3785
Synonymous	1.05	202	222	0.910	0.0000114	2366
Loss of Function	6.83	1	56.3	0.0178	0.00000305	719

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000365	0.0000352
Middle Eastern	0.0000544	0.0000544
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);Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);Mineral absorption - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Vitamin D Receptor Pathway;Splicing factor NOVA regulated synaptic proteins;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;C-MYB transcription factor network;Reduction of cytosolic Ca++ levels;Platelet calcium homeostasis;Platelet homeostasis (Consensus)

Recessive Scores

• pRec: 0.230

Intolerance Scores

• loftool: 0.00551
• rvis_EVS: -1.02
• rvis_percentile_EVS: 7.94

Haploinsufficiency Scores

• pHI: 0.932
• hipred: Y
• hipred_score: 0.768
• ghis: 0.625

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.814

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atp2b1
• Phenotype: limbs/digits/tail phenotype; digestive/alimentary phenotype; renal/urinary system phenotype; skeleton phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: atp2b1a
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: has fewer parts of type

Gene ontology

• Biological process: neural retina development;cellular calcium ion homeostasis;brain development;aging;response to cold;ion transmembrane transport;regulation of cytosolic calcium ion concentration;calcium ion transmembrane transport;cellular response to vitamin D;cellular response to corticosterone stimulus;ATP hydrolysis coupled cation transmembrane transport;regulation of presynaptic cytosolic calcium ion concentration;regulation of cardiac conduction;calcium ion export across plasma membrane
• Cellular component: nucleus;plasma membrane;integral component of plasma membrane;cytoplasmic side of plasma membrane;membrane;basolateral plasma membrane;apical plasma membrane;dendritic spine membrane;neuronal cell body membrane;membrane raft;extracellular exosome;glutamatergic synapse;GABA-ergic synapse;integral component of presynaptic active zone membrane
• Molecular function: calcium-transporting ATPase activity;protein binding;calmodulin binding;ATP binding;calcium ion transmembrane transporter activity;PDZ domain binding;metal ion binding;calcium-transporting ATPase activity involved in regulation of presynaptic cytosolic calcium ion concentration