ATP2B3

protein-coding

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

Gene summary

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 3. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Previous symbols:

SCAX1
CLA2

MANE transcript

NM_001001344.3

Inheritance

ClinVar variants

P:7U:152B:97

Top phenotype

Spinocerebellar ataxia, X-linked 1

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chrX:153,517,642-153,582,939

External References & Databases

Ensembl (ENSG00000067842)

Transcript & Mutation Effects

hg38 • Region Span ~65.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

X-linked non progressive cerebellar ataxiaSUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010404

Submitter: Orphanet

X-linked progressive cerebellar ataxiaMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0010547

Submitter: PanelApp Australia

X-linked progressive cerebellar ataxiaMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0010547

Submitter: Ambry Genetics

X-linked progressive cerebellar ataxiaMODERATE

Inheritance Pattern: Unknown

Disease ID:MONDO:0010547

Submitter: Genomics England PanelApp

X-linked progressive cerebellar ataxiaSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010547

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spinocerebellar ataxia, X-linked 1XL

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 10797423; 22912398

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ATP2B3 variants in ClinVar

20 Conditions Cataloged

Inborn genetic diseasesTotal: 104

not providedTotal: 96

not specifiedTotal: 59

X-linked progressive cerebellar ataxiaTotal: 32

ATP2B3-related disorderTotal: 22

Aldosterone-producing adrenal cortex adenomaTotal: 3

See casesTotal: 2

Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001001344.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	46 clinvar	10 clinvar	60
missense		6 clinvar	139 clinvar	37 clinvar	2 clinvar	184
nonsense		1 clinvar				1
start loss						0
frameshift			2 clinvar	2 clinvar		4
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	7	152	85	12	256

Highest pathogenic variant AF is 0.000014951955

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001001344.3	RefSeq	NP_001001344.1	20	MANE Select
ENST00000263519.5	Ensembl	ENSP00000263519.4	20	MANE Select
NM_001388360.1	RefSeq	NP_001375289.1	21	Standard
NM_001388361.1	RefSeq	NP_001375290.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

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

Molecular Function

calcium-transporting ATPase activity
protein binding
calmodulin binding
ATP binding
calcium ion transmembrane transporter activity

Cellular Component

Golgi apparatus
plasma membrane
integral component of plasma membrane
presynapse
glutamatergic synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263519
Coding exons: 20
Length: 65264
Individuals with no LoFs: 125737
Homozygous LoFs: 2
Heterozygous LoFs: 4
Defined: 125743
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.75	405	593	0.683	0.0000555	7960
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000076	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000072	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000050	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.;

Recessive Scores

pRec: 0.148

Intolerance Scores

LoFtool: 0.000758
RVIS EVS: -1.68
RVIS percentile EVS: 2.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

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