ATP12A

protein-coding

ATPase H+/K+ transporting non-gastric alpha2 subunit, the group of ATPase H+/K+ transporting

Gene summary

The protein encoded by this gene belongs to the family of P-type cation transport ATPases. This gene encodes a catalytic subunit of the ouabain-sensitive H+/K+ -ATPase that catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. It is also responsible for potassium absorption in various tissues. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

Previous symbols:

ATP1AL1

MANE transcript

NM_001676.7

Inheritance

—

ClinVar variants

U:155B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr13:24,680,408-24,712,472

External References & Databases

Ensembl (ENSG00000075673)

Transcript & Mutation Effects

hg38 • Region Span ~32.1 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 ATP12A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 158

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001676.7. 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				5 clinvar		5
missense			153 clinvar	2 clinvar		155
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	155	7	0	162

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001676.7	RefSeq	NP_001667.4	23	MANE Select
ENST00000381946.5	Ensembl	ENSP00000371372.3	23	MANE Select
NM_001185085.2	RefSeq	NP_001172014.1	23	Standard
ENST00000218548.10	Ensembl	ENSP00000218548.6	23	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Oxidative phosphorylation - Homo sapiens (human)
Ion channel transport
Purine metabolism
Transport of small molecules
Ion transport by P-type ATPases

Biological Process

cellular sodium ion homeostasis
regulation of pH
establishment or maintenance of transmembrane electrochemical gradient
ATP hydrolysis coupled proton transport
cellular potassium ion homeostasis

Molecular Function

sodium:potassium-exchanging ATPase activity
ATP binding
potassium:proton exchanging ATPase activity
metal ion binding

Cellular Component

plasma membrane
potassium:proton exchanging ATPase complex
basolateral plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000218548
Coding exons: 23
Length: 31373
Individuals with no LoFs: 125260
Homozygous LoFs: 3
Heterozygous LoFs: 485
Defined: 125748
p: 0.00194

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.834	547	605	0.905	0.0000337	6856
Missense (PolyPhen)		229	248.64	0.92103		2894
Synonymous	0.352	235	242	0.971	0.0000149	2052
Loss of Function	2.60	29	48.5	0.598	0.00000229	588

Population LoF Frequency

Population	CAF	p-value	Status
African	0.017	0.017	notable
Latino/Admixed American	0.0011	0.0011	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00098	0.00087	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00062	0.00059	rare
South Asian	0.0029	0.0028	notable
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. Responsible for potassium absorption in various tissues.;

Recessive Scores

pRec: 0.235

Intolerance Scores

LoFtool: 0.0580
RVIS EVS: -1.32
RVIS percentile EVS: 4.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.746

Gene Damage Prediction

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