ATP2B3

ATPase plasma membrane Ca2+ transporting 3, the group of ATPases Ca2+ transporting|Cilia and flagella associated

Basic information

Region (hg38): X:153517641-153582939

Previous symbols: [ "SCAX1", "CLA2" ]

Links

ENSG00000067842 ∙ NCBI:492 ∙ OMIM:300014 ∙ HGNC:816 ∙ Uniprot:Q16720 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• X-linked progressive cerebellar ataxia (Moderate), mode of inheritance: Unknown
• X-linked progressive cerebellar ataxia (Limited), mode of inheritance: XL
• X-linked non progressive cerebellar ataxia (Supportive), mode of inheritance: XL
• X-linked progressive cerebellar ataxia (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia, X-linked 1	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	10797423; 22912398

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATP2B3 gene.

• not provided (72 variants)
• Inborn genetic diseases (37 variants)
• X-linked progressive cerebellar ataxia (27 variants)
• not specified (11 variants)
• See cases (2 variants)
• Spastic ataxia (1 variants)
• 8 conditions (1 variants)
• Arthrogryposis multiplex congenita;Fetal akinesia deformation sequence 1 (1 variants)
• Neonatal hypotonia (1 variants)
• Neurodevelopmental disorder (1 variants)
• ATP2B3-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP2B3 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				15	12	27
missense		6	62	14	2	84
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			2	1	3	6
non coding			1	3	8	12
Total	0	6	65	32	22

Highest pathogenic variant AF is 0.00000882

Variants in ATP2B3

This is a list of pathogenic ClinVar variants found in the ATP2B3 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-153536245-A-G		ATP2B3-related disorder	Likely benign (Jul 02, 2019)
X-153536251-G-A		X-linked progressive cerebellar ataxia	Uncertain significance (May 09, 2021)
X-153536304-G-C			Likely benign (Dec 01, 2022)
X-153536336-C-G			Uncertain significance (Nov 01, 2023)
X-153536369-G-A			Uncertain significance (Aug 24, 2022)
X-153536377-G-A		Spastic ataxia	Likely pathogenic (Jul 12, 2021)
X-153536382-G-A		ATP2B3-related disorder	Likely benign (Nov 25, 2019)
X-153536395-G-A			Uncertain significance (Nov 01, 2023)
X-153536398-G-A		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
X-153536435-TGAAGACCTC-AGACTT			Uncertain significance (Dec 09, 2020)
X-153536438-A-G		Inborn genetic diseases	Likely benign (Mar 07, 2024)
X-153536440-A-G			Uncertain significance (Jun 17, 2016)
X-153536444-C-T		Arthrogryposis multiplex congenita;Fetal akinesia deformation sequence 1	Likely pathogenic (Jun 28, 2019)
X-153536462-C-A			Benign (Dec 31, 2019)
X-153541342-T-A		See cases	Uncertain significance (May 09, 2023)
X-153541349-C-T		not specified	Likely benign (Sep 22, 2017)
X-153541364-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 29, 2022)
X-153541366-G-A		ATP2B3-related disorder	Benign (Oct 31, 2019)
X-153541394-A-G			Uncertain significance (May 24, 2017)
X-153541474-C-T			Likely benign (Oct 23, 2018)
X-153541480-C-A			Benign (Jul 06, 2018)
X-153541537-G-C			Benign (Jul 04, 2018)
X-153541663-G-A		X-linked progressive cerebellar ataxia	Benign/Likely benign (May 11, 2022)
X-153541734-G-T		X-linked progressive cerebellar ataxia • Inborn genetic diseases	Uncertain significance (Nov 03, 2023)
X-153541735-C-T		Inborn genetic diseases	Uncertain significance (Jun 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATP2B3	protein_coding	protein_coding	ENST00000263519	20	65264

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000548	125737	2	4	125743	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.75	405	593	0.683	0.0000555	7960
Missense in Polyphen		137	262.81	0.52129		3357
Synonymous	-0.144	279	276	1.01	0.0000290	2481
Loss of Function	5.00	3	34.9	0.0861	0.00000251	568

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000760	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000722	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000496	0.0000352
Middle Eastern	0.0000722	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);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: 0.148

Intolerance Scores

• loftool: 0.000758
• rvis_EVS: -1.68
• rvis_percentile_EVS: 2.68

Haploinsufficiency Scores

• pHI: 0.366
• hipred: Y
• hipred_score: 0.752
• ghis: 0.563

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atp2b3

Gene ontology

• Biological process: cellular calcium ion homeostasis;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 cardiac conduction;calcium ion export across plasma membrane
• Cellular component: Golgi apparatus;plasma membrane;integral component of plasma membrane;presynapse;glutamatergic synapse;GABA-ergic synapse;extracellular vesicle
• 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