ATP1A4

protein-coding

ATPase Na+/K+ transporting subunit alpha 4, the group of ATPase Na+/K+ transporting subunits

Gene summary

The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+ -ATPases. Na+/K+ -ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes an alpha 4 subunit. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Previous symbols:

ATP1AL2

MANE transcript

NM_144699.4

Inheritance

ClinVar variants

U:162B:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr1:160,151,586-160,186,980

External References & Databases

Ensembl (ENSG00000132681)

Transcript & Mutation Effects

hg38 • Region Span ~35.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial hemiplegic migraineLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0000700

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ATP1A4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 153

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_144699.4. 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 clinvar	6
missense			157 clinvar	6 clinvar	2 clinvar	165
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	162	7	5	174

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_144699.4	RefSeq	NP_653300.2	22	MANE Select
ENST00000368081.9	Ensembl	ENSP00000357060.4	22	MANE Select
NM_001001734.2	RefSeq	NP_001001734.1	5	Standard
ENST00000469023.5	Ensembl	ENSP00000500965.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Aldosterone synthesis and secretion - Homo sapiens (human)
Cardiac muscle contraction - Homo sapiens (human)
Thyroid hormone synthesis - Homo sapiens (human)
Protein digestion and absorption - Homo sapiens (human)
Bile secretion - Homo sapiens (human)

Biological Process

potassium ion transport
sodium ion transport
cellular sodium ion homeostasis
spermatogenesis
fertilization

Molecular Function

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

Cellular Component

plasma membrane
integral component of plasma membrane
sodium:potassium-exchanging ATPase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368081
Coding exons: 22
Length: 35408
Individuals with no LoFs: 125451
Homozygous LoFs: 1
Heterozygous LoFs: 296
Defined: 125748
p: 0.00118

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.490	573	607	0.944	0.0000346	6729
Missense (PolyPhen)		258	292.51	0.88203		3257
Synonymous	-0.669	250	237	1.06	0.0000150	2046
Loss of Function	1.93	39	54.3	0.718	0.00000317	568

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00055	0.00055	rare
Latino/Admixed American	0.00084	0.00084	rare
Ashkenazi Jewish	0.0032	0.0032	notable
East Asian	0.0047	0.0047	notable
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00064	0.00062	rare
South Asian	0.0019	0.0019	notable
Other	0.0016	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients. Plays a role in sperm motility.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.123
RVIS EVS: 0.55
RVIS percentile EVS: 81.13

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.105

Gene Damage Prediction

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