ATP13A5

protein-coding

ATPase 13A5, the group of ATPase orphan transporters

Gene summary

This gene encodes a member of the P5 subfamily of P-type transport ATPases. P-type ATPases form a large superfamily of cation and lipid pumps that transport inorganic cations and other substrates across cell membranes. P5 ATPases are localized to membranes of the endoplasmic reticulum (ER) and serve many important functions including transport of cargo proteins to the Golgi, glycosylation and cell wall biosynthesis, control of protein insertion orientation, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) degradation, and sensitivity to unfolded protein response (UPR) activators. The encoded protein is organized into three cytoplasmic domains (A, P, and N) and two membrane-embedded domains (T and S). The N-domain binds ATP and serves as a built-in protein kinase, which phosphorylates the P-domain. The A-domain is an intrinsic protein phosphatase, which dephosphorylates the P-domain once during each catalytic cycle. [provided by RefSeq, Jul 2017]

MANE transcript

NM_198505.4

Inheritance

—

ClinVar variants

U:161B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.06

Max pathogenic AF

—

Genomic locus

chr3:193,274,789-193,378,820

External References & Databases

Ensembl (ENSG00000187527)

Transcript & Mutation Effects

hg38 • Region Span ~104.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ATP13A5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 161

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_198505.4. 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				2 clinvar	1 clinvar	3
missense			156 clinvar	6 clinvar		162
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar		1 clinvar	3
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	161	8	2	171

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_198505.4	RefSeq	NP_940907.2	30	MANE Select
ENST00000342358.9	Ensembl	ENSP00000341942.4	30	MANE Select
ENST00000446087.1	Ensembl	ENSP00000389416.1	5	Standard
ENST00001142036.1	Ensembl	ENSP00000807963.1	30	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ion channel transport
Transport of small molecules
Ion transport by P-type ATPases

Biological Process

cellular calcium ion homeostasis
ion transmembrane transport
ATP hydrolysis coupled cation transmembrane transport

Molecular Function

ATP binding
cation-transporting ATPase activity
metal ion binding

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000342358
Coding exons: 30
Length: 104054
Individuals with no LoFs: 119078
Homozygous LoFs: 99
Heterozygous LoFs: 6571
Defined: 125748
p: 0.0269

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.606	601	644	0.933	0.0000325	7935
Missense (PolyPhen)		201	249.43	0.80583		3234
Synonymous	0.664	227	240	0.945	0.0000126	2313
Loss of Function	-0.445	72	68.0	1.06	0.00000323	842

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0091	0.0085	notable
Latino/Admixed American	0.017	0.017	notable
Ashkenazi Jewish	0.010	0.010	notable
East Asian	0.0019	0.0019	notable
Finnish	0.050	0.050	notable
European (Non-Finnish)	0.039	0.039	notable
South Asian	0.0089	0.0088	notable
Other	0.027	0.026	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0798

Intolerance Scores

LoFtool: 0.263
RVIS EVS: 2.04
RVIS percentile EVS: 97.72

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.125

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High