ATP13A3

protein-coding

ATPase 13A3, the group of ATPase orphan transporters

Gene summary

ATP13A3 is a member of the P-type ATPase family of proteins that transport a variety of cations across membranes. Other P-type ATPases include ATP7B (MIM 606882) and ATP7A (MIM 300011).[supplied by OMIM, Aug 2008]

MANE transcript

NM_001367549.1

Inheritance

SD, AD, AR

ClinVar variants

P:9U:160B:68

Top phenotype

Pulmonary hypertension, primary, 5

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr3:194,402,672-194,498,364

External References & Databases

Ensembl (ENSG00000133657)

Transcript & Mutation Effects

hg38 • Region Span ~95.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pulmonary arterial hypertensionDEFINITIVE

Inheritance Pattern: SD

Disease ID:MONDO:0015924

Submitter: ClinGen

ATP13A3 encodes an ATPase that plays a role in polyamine transport to a variety of cations across the membrane. This gene has been seen to be related with definitive evidence for pulmonary arterial hypertension by several studies [Gräf et al., 2018; Barozzi et al., 2019; Lerche et al., 2019; Zhu et al., 2019; Wang et al., 2019 and Machado et al., 2021]. The mode of inheritance of ATP13A3 showed a semi-dominant pattern and the majority of the variants detected were missense, although nonsense and frameshift variants have also been detected. Functional assays confirmed that ATP13A3 is expressed in primary pulmonary arterial smooth muscle cells, endothelial cells and blood outgrowth endothelial cells from patients. ATP13A3 knockdown by siRNA in BOECs showed decreased proliferation and BOECs transfected with siRNA of ATP13A3 showed increased apoptosis [Gräf et al., 2018].

pulmonary hypertension, primary, 5STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0009935

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Pulmonary hypertension, primary, 5AR

Manifestation: Cardiovascular

Intervention: Cardiovascular

Rationale: Individuals with Pulmonary hypertension, primary, may manifest at variable ages, and awareness may allow surveillance, diagnosis of sequelae, and prompt management (including medical and/or surgical management) of disease

Refs: 34493544

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ATP13A3 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 152

not specifiedTotal: 150

ATP13A3-related disorderTotal: 21

Pulmonary hypertension, primary, 5Total: 9

Pulmonary arterial hypertensionTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001367549.1. 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			3 clinvar	45 clinvar	6 clinvar	54
missense		2 clinvar	147 clinvar	14 clinvar	3 clinvar	166
nonsense	1 clinvar	1 clinvar	1 clinvar			3
start loss			1 clinvar			1
frameshift	3 clinvar	1 clinvar				4
splice donor/acceptor (+/-2bp)	1 clinvar		8 clinvar			9
Total	5	4	160	59	9	237

Highest pathogenic variant AF is 0.000013699719

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 69 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001367549.1	RefSeq	NP_001354478.1	32	MANE Select
ENST00000645319.2	Ensembl	ENSP00000494937.2	32	MANE Select
NM_001374836.1	RefSeq	NP_001361765.1	31	Standard
NM_001437993.1	RefSeq	NP_001424922.1	31	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cation transport
cellular calcium ion homeostasis

Molecular Function

ATP binding
ATPase activity
metal ion binding

Cellular Component

cell
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000439040
Coding exons: 31
Length: 95693
Individuals with no LoFs: 124805
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 124821
p: 0.0000641

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.01	444	662	0.670	0.0000339	8070
Missense (PolyPhen)		66	191.34	0.34494		2298
Synonymous	-0.136	230	227	1.01	0.0000124	2312
Loss of Function	6.59	8	65.5	0.122	0.00000305	843

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0	0.0	absent
Finnish	0.000093	0.000093	rare
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0	0.0	absent
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0969

Intolerance Scores

LoFtool: 0.124
RVIS EVS: -0.97
RVIS percentile EVS: 8.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.403

Gene Damage Prediction

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