ATP1B4
protein-codingATPase Na+/K+ transporting family member beta 4
Gene summary
This gene has been found in all vertebrate genomes sequenced to date. However, this gene has undergone a change in function in placental mammals compared to other species. Specifically, in fish, avian, and amphibian species, this gene encodes plasma membrane-bound beta-subunits of Na,K-ATPase. In placental mammals, the encoded protein interacts with the nuclear transcriptional coregulator SKIP and may be involved in the regulation of TGF-beta signaling. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~21.2 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 ATP1B4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001142447.3. 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 | 3 | 3 | 6 | |||
| missense | 54 | 3 | 57 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 59 | 7 | 0 | 66 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001135919.1 | 8 | MANE Select | |
| Ensembl | ENSP00000218008.3 | 8 | MANE Select | |
| RefSeq | NP_036201.1 | 8 | Standard | |
| Ensembl | ENSP00000355346.3 | 8 | 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
- regulation of transcription, DNA-templated
- monovalent inorganic cation transport
- positive regulation of transcription by RNA polymerase II
Molecular Function
- protein binding
- monovalent inorganic cation transmembrane transporter activity
Cellular Component
- nucleus
- nuclear envelope
- nuclear inner membrane
- integral component of plasma membrane
- sodium:potassium-exchanging ATPase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000218008
- Coding exons
- 8
- Length
- 20260
- Individuals with no LoFs
- 125703
- Homozygous LoFs
- 7
- Heterozygous LoFs
- 13
- Defined
- 125723
- p
- 0.0000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.224 | 136 | 144 | 0.947 | 0.0000113 | 2371 |
| Missense (PolyPhen) | 51 | 55.897 | 0.9124 | 987 | ||
| Synonymous | -1.18 | 65 | 54.0 | 1.20 | 0.00000442 | 645 |
| Loss of Function | 1.80 | 8 | 15.7 | 0.509 | 0.00000131 | 234 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00029 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00012 | 0.000088 | rare |
| South Asian | 0.00011 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May act as a transcriptional coregulator during muscle development through its interaction with SNW1. Has lost its ancestral function as a Na,K-ATPase beta-subunit. {ECO:0000269|PubMed:17592128}.;
Recessive Scores
- pRec
- 0.100
Intolerance Scores
- LoFtool
- 0.812
- RVIS EVS
- 0.17
- RVIS percentile EVS
- 65.76
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.159
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |