ATP1A4

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

Basic information

Region (hg38): 1:160151586-160186980

Previous symbols: [ "ATP1AL2" ]

Links

ENSG00000132681 ∙ NCBI:480 ∙ OMIM:607321 ∙ HGNC:14073 ∙ Uniprot:Q13733 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATP1A4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP1A4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	3	4
missense			55	3	2	60
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	56	4	5

Variants in ATP1A4

This is a list of pathogenic ClinVar variants found in the ATP1A4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-160152046-G-A			Benign (Apr 16, 2018)
1-160152047-C-T		not specified	Uncertain significance (Nov 09, 2023)
1-160152072-C-T		not specified	Uncertain significance (Mar 28, 2023)
1-160152095-C-A			Benign (Apr 16, 2018)
1-160152118-C-G		not specified	Uncertain significance (May 16, 2024)
1-160152186-T-A		not specified	Uncertain significance (Jun 02, 2023)
1-160153181-C-T		not specified	Uncertain significance (Dec 01, 2022)
1-160153199-C-G		not specified	Uncertain significance (Dec 19, 2022)
1-160155055-A-G		not specified	Uncertain significance (Oct 03, 2023)
1-160155076-T-C		not specified	Uncertain significance (May 15, 2024)
1-160155082-G-A		not specified	Uncertain significance (Nov 30, 2022)
1-160155108-C-A		not specified	Uncertain significance (May 29, 2024)
1-160155114-A-C		not specified	Uncertain significance (Aug 23, 2021)
1-160155152-C-T			Benign (Jul 23, 2018)
1-160155214-A-G		not specified	Uncertain significance (Mar 21, 2023)
1-160156072-G-A		not specified	Uncertain significance (Aug 11, 2022)
1-160158998-A-C			Benign (Jul 23, 2018)
1-160159018-G-A		not specified	Uncertain significance (Feb 16, 2023)
1-160159066-A-G		not specified	Uncertain significance (Apr 12, 2023)
1-160159111-G-A		not specified	Uncertain significance (Feb 24, 2023)
1-160159442-C-G		not specified	Uncertain significance (Aug 03, 2022)
1-160164183-C-T		not specified	Uncertain significance (Mar 02, 2023)
1-160164253-C-T			Likely benign (Jul 23, 2018)
1-160166561-C-T		not specified	Uncertain significance (Mar 06, 2023)
1-160166562-G-A		not specified	Uncertain significance (Jul 20, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATP1A4	protein_coding	protein_coding	ENST00000368081	22	35408

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.14e-20	0.491	125451	1	296	125748	0.00118

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.490	573	607	0.944	0.0000346	6729
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00139	0.00139
Ashkenazi Jewish	0.00318	0.00318
East Asian	0.00468	0.00469
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000645	0.000624
Middle Eastern	0.00468	0.00469
South Asian	0.00193	0.00193
Other	0.00163	0.00147

dbNSFP

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.
• Pathway: 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);Carbohydrate digestion and absorption - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Proximal tubule bicarbonate reclamation - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human);Aldosterone-regulated sodium reabsorption - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);Mineral absorption - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Levomethadyl Acetate Action Action Pathway;Polythiazide Action Pathway;Methyclothiazide Action Pathway;Bumetanide Action Pathway;Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Fluoxetine Action Pathway;Citalopram Action Pathway;Escitalopram Action Pathway;Imipramine Action Pathway;Desipramine Action Pathway;Spironolactone Action Pathway;Eplerenone Action Pathway;Triamterene Action Pathway;Amiloride Action Pathway;Levallorphan Action Pathway;Dimethylthiambutene Action Pathway;Ethylmorphine Action Pathway;Pentazocine Action Pathway;Naltrexone Action Pathway;Buprenorphine Action Pathway;Alvimopan Action Pathway;Naloxone Action Pathway;Dihydromorphine Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Trehalose Degradation;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Ethacrynic Acid Action Pathway;Quinethazone Action Pathway;Bendroflumethiazide Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Nicotine Action Pathway;Chlorthalidone Action Pathway;Trichlormethiazide Action Pathway;Nalbuphine Action Pathway;Ketobemidone Action Pathway;Iminoglycinuria;Lysinuric Protein Intolerance;Lidocaine (Local Anaesthetic) Action Pathway;Mepivacaine Action Pathway;Chloroprocaine Action Pathway;Cocaine Action Pathway;Dibucaine Action Pathway;Levobupivacaine Action Pathway;Benzocaine Action Pathway;Bupivacaine Action Pathway;Muscle/Heart Contraction;Blue diaper syndrome;Lysinuric protein intolerance (LPI);Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Levorphanol Action Pathway;Propoxyphene Action Pathway;Tramadol Action Action Pathway;Bupranolol Action Pathway;Diphenoxylate Action Pathway;Anileridine Action Pathway;Methadone Action Pathway;Oxycodone Action Pathway;Oxybuprocaine Action Pathway;Prilocaine Action Pathway;Procaine Action Pathway;Proparacaine Action Pathway;Ropivacaine Action Pathway;Codeine Action Pathway;Morphine Action Pathway;Heroin Action Pathway;Nebivolol Action Pathway;Cystinuria;Amlodipine Action Pathway;Verapamil Action Pathway;Indapamide Action Pathway;Furosemide Action Pathway;Torsemide Action Pathway;Hartnup Disorder;Glucose Transporter Defect (SGLT2);Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Kidney Function;Alfentanil Action Pathway;Oxymorphone Action Pathway;Hydrocodone Action Pathway;Hydromorphone Action Pathway;Sufentanil Action Pathway;Remifentanil Action Pathway;Fentanyl Action Pathway;Carfentanil Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Glucose Transporter Defect (SGLT2);Carvedilol Action Pathway;Labetalol Action Pathway;Lactose Degradation;Lactose Intolerance;Metolazone Action Pathway;Hydrochlorothiazide Action Pathway;Cyclothiazide Action Pathway;Hydroflumethiazide Action Pathway;3-Methylthiofentanyl Action Pathway;Methadyl Acetate Action Pathway;Chlorothiazide Action Pathway;Dezocine Action Pathway;Calcium Regulation in the Cardiac Cell;Ion channel transport;Purine metabolism;Ion homeostasis;Transport of small molecules;Cardiac conduction;Muscle contraction;Ion transport by P-type ATPases (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.123
• rvis_EVS: 0.55
• rvis_percentile_EVS: 81.13

Haploinsufficiency Scores

• pHI: 0.118
• hipred: Y
• hipred_score: 0.535

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.105

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atp1a4
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; reproductive system phenotype

Gene ontology

• Biological process: potassium ion transport;sodium ion transport;cellular sodium ion homeostasis;spermatogenesis;fertilization;establishment or maintenance of transmembrane electrochemical gradient;ATP hydrolysis coupled proton transport;cellular potassium ion homeostasis;flagellated sperm motility;regulation of cellular pH;sodium ion export across plasma membrane;regulation of membrane potential;potassium ion import across plasma membrane
• Cellular component: plasma membrane;integral component of plasma membrane;sodium:potassium-exchanging ATPase complex
• Molecular function: sodium:potassium-exchanging ATPase activity;ATP binding;metal ion binding