FXYD4
protein-codingFXYD domain containing ion transport regulator 4
Gene summary
This gene encodes a member of a family of small membrane proteins that share a 35-amino acid signature sequence domain, beginning with the sequence PFXYD and containing 7 invariant and 6 highly conserved amino acids. The approved human gene nomenclature for the family is FXYD-domain containing ion transport regulator. FXYD4, originally named CHIF for channel-inducing factor, has been shown to modulate the properties of the Na,K-ATPase, as has FXYD2, also known as the gamma subunit of the Na,K-ATPase, and FXYD7. Transmembrane topology has been established for FXYD4 and two family members (FXYD1 and FXYD2), with the N-terminus extracellular and the C-terminus on the cytoplasmic side of the membrane. Alternatively spliced transcript variants encoding the same protein have been found.[provided by RefSeq, May 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.7 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 FXYD4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_173160.3. 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 | 0 | |||||
| missense | 20 | 20 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 25 | 0 | 0 | 25 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_775183.1 | 7 | MANE Select | |
| Ensembl | ENSP00000473361.1 | 7 | MANE Select | |
| Ensembl | ENSP00000483791.1 | 7 | Standard | |
| Ensembl | ENSP00000483791.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Aldosterone-regulated sodium reabsorption - Homo sapiens (human)
- Ion channel transport
- Ion homeostasis
- Transport of small molecules
- Cardiac conduction
Biological Process
- potassium ion transmembrane transport
- regulation of sodium ion transmembrane transporter activity
Molecular Function
- potassium channel activity
- sodium channel regulator activity
- ATPase binding
- ion channel regulator activity
Cellular Component
- plasma membrane
- sodium:potassium-exchanging ATPase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000476166
- Coding exons
- 7
- Length
- 4694
- Individuals with no LoFs
- 125711
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 37
- Defined
- 125748
- p
- 0.000147
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.303 | 52 | 46.2 | 1.13 | 0.00000246 | 566 |
| Missense (PolyPhen) | 9 | 6.6592 | 1.3515 | 67 | ||
| Synonymous | -0.273 | 21 | 19.5 | 1.08 | 0.00000129 | 168 |
| Loss of Function | 0.605 | 6 | 7.83 | 0.767 | 3.43e-7 | 92 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00060 | 0.00060 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
Intolerance Scores
- LoFtool
- 0.713
- RVIS EVS
- 0.35
- RVIS percentile EVS
- 73.97
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.204
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |