ATP1B1
protein-codingATPase Na+/K+ transporting subunit beta 1, the group of ATPase Na+/K+ transporting subunits
Gene summary
The protein encoded by this gene belongs to the family of Na+/K+ and H+/K+ ATPases beta chain proteins, 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 beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane. The glycoprotein subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes a beta 1 subunit. Alternatively spliced transcript variants encoding different isoforms have been described, but their biological validity is not known. [provided by RefSeq, Mar 2010]
- ATP1B
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~205.3 kbGenCC 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 ATP1B1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001677.4. 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 | 4 | 3 | 7 | |||
| missense | 25 | 2 | 27 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 32 | 6 | 3 | 41 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001668.1 | 6 | MANE Select | |
| Ensembl | ENSP00000356789.3 | 6 | MANE Select | |
| Ensembl | ENSP00000356790.1 | 6 | Standard | |
| Ensembl | ENSP00000477015.2 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| atp1b1a | Danio rerio | Structure: epidermal cell Quality: aggregated abnormal |
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
- response to hypoxia
- cellular calcium ion homeostasis
- cellular sodium ion homeostasis
- cell adhesion
- establishment or maintenance of transmembrane electrochemical gradient
Molecular Function
- ATPase activator activity
- sodium:potassium-exchanging ATPase activity
- protein binding
- ATP binding
- protein C-terminus binding
Cellular Component
- plasma membrane
- sodium:potassium-exchanging ATPase complex
- caveola
- intercalated disc
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367816
- Coding exons
- 6
- Length
- 27026
- Individuals with no LoFs
- 116318
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 116319
- p
- 0.00000430
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.00 | 97 | 171 | 0.569 | 0.00000926 | 1985 |
| Missense (PolyPhen) | 12 | 53.156 | 0.22575 | 588 | ||
| Synonymous | -0.00899 | 64 | 63.9 | 1.00 | 0.00000357 | 554 |
| Loss of Function | 4.10 | 0 | 19.5 | 0.00 | 0.00000137 | 195 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000092 | 0.0000092 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane. {ECO:0000269|PubMed:19694409}.;
Recessive Scores
- pRec
- 0.248
Intolerance Scores
- LoFtool
- 0.140
- RVIS EVS
- -0.45
- RVIS percentile EVS
- 24
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.719
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |