ATP2B4

protein-coding

ATPase plasma membrane Ca2+ transporting 4, the group of ATPases Ca2+ transporting|Small nucleolar RNA protein coding host genes

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

Previous symbols:

ATP2B2
MXRA1

MANE transcript

NM_001684.5

Inheritance

ClinVar variants

U:183B:84

Top phenotype

ATP2B4-related disorder

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr1:203,626,832-203,744,081

External References & Databases

Ensembl (ENSG00000058668)

Transcript & Mutation Effects

hg38 • Region Span ~117.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary spastic paraplegiaMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0019064

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ATP2B4 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 173

not specifiedTotal: 134

ATP2B4-related disorderTotal: 28

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001684.5. 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			1 clinvar	41 clinvar	16 clinvar	58
missense			175 clinvar	18 clinvar	9 clinvar	202
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	183	59	25	267

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001684.5	RefSeq	NP_001675.3	20	MANE Select
ENST00000357681.10	Ensembl	ENSP00000350310.5	20	MANE Select
NM_001001396.3	RefSeq	NP_001001396.1	21	Standard
NM_001365783.2	RefSeq	NP_001352712.1	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

neural retina development
regulation of transcription by RNA polymerase II
cellular calcium ion homeostasis
spermatogenesis
negative regulation of nitric oxide mediated signal transduction

Molecular Function

calcium-transporting ATPase activity
protein binding
calmodulin binding
ATP binding
sodium channel regulator activity

Cellular Component

plasma membrane
integral component of plasma membrane
caveola
membrane
basolateral plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357681
Coding exons: 20
Length: 117521
Individuals with no LoFs: 125711
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 125748
p: 0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.25	537	705	0.762	0.0000412	7904
Missense (PolyPhen)		203	330.46	0.61429		3744
Synonymous	0.0507	267	268	0.996	0.0000152	2419
Loss of Function	4.85	16	54.7	0.292	0.00000321	594

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00014	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00023	0.00023	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Calcium/calmodulin-regulated and magnesium-dependent enzyme that catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell (PubMed:8530416). By regulating sperm cell calcium homeostasis, may play a role in sperm motility (By similarity). {ECO:0000250|UniProtKB:Q6Q477, ECO:0000269|PubMed:8530416}.;

Recessive Scores

pRec: 0.179

Intolerance Scores

LoFtool: 0.0312
RVIS EVS: -0.83
RVIS percentile EVS: 11.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.922

Gene Damage Prediction

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