FXYD1
protein-codingFXYD domain containing ion transport regulator 1
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. Mouse FXYD5 has been termed RIC (Related to Ion Channel). FXYD2, also known as the gamma subunit of the Na,K-ATPase, regulates the properties of that enzyme. FXYD1 (phospholemman), FXYD2 (gamma), FXYD3 (MAT-8), FXYD4 (CHIF), and FXYD5 (RIC) have been shown to induce channel activity in experimental expression systems. Transmembrane topology has been established for two family members (FXYD1 and FXYD2), with the N-terminus extracellular and the C-terminus on the cytoplasmic side of the membrane. The protein encoded by this gene is a plasma membrane substrate for several kinases, including protein kinase A, protein kinase C, NIMA kinase, and myotonic dystrophy kinase. It is thought to form an ion channel or regulate ion channel activity. Transcript variants with different 5' UTR sequences have been described in the literature. [provided by RefSeq, Jul 2008]
- PLM
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.3 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 FXYD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021902.4. 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 | 0 | |||||
| missense | 9 | 9 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 15 | 0 | 0 | 15 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_068702.1 | 6 | MANE Select | |
| Ensembl | ENSP00000343314.3 | 6 | MANE Select | |
| RefSeq | NP_001265646.1 | 6 | Standard | |
| RefSeq | NP_001265647.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- cAMP signaling pathway - Homo sapiens (human)
- Ion channel transport
- Ion homeostasis
- Transport of small molecules
- Cardiac conduction
Biological Process
- potassium ion transport
- sodium ion transport
- chloride transport
- muscle contraction
- regulation of heart contraction
Molecular Function
- chloride channel activity
- sodium channel regulator activity
- ion channel binding
- ion channel regulator activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- sodium:potassium-exchanging ATPase complex
- caveola
- intercalated disc
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000588081
- Coding exons
- 6
- Length
- 4302
- Individuals with no LoFs
- 125691
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125700
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.525 | 44 | 55.0 | 0.801 | 0.00000285 | 589 |
| Missense (PolyPhen) | 12 | 19.604 | 0.61211 | 221 | ||
| Synonymous | -0.977 | 28 | 22.1 | 1.26 | 0.00000130 | 175 |
| Loss of Function | 1.85 | 2 | 7.44 | 0.269 | 3.25e-7 | 84 |
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) | 0.000044 | 0.000044 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Associates with and regulates the activity of the sodium/potassium-transporting ATPase (NKA) which transports Na(+) out of the cell and K(+) into the cell. Inhibits NKA activity in its unphosphorylated state and stimulates activity when phosphorylated. Reduces glutathionylation of the NKA beta-1 subunit ATP1B1, thus reversing glutathionylation-mediated inhibition of ATP1B1. Contributes to female sexual development by maintaining the excitability of neurons which secrete gonadotropin-releasing hormone. {ECO:0000250|UniProtKB:O08589, ECO:0000250|UniProtKB:P56513, ECO:0000250|UniProtKB:Q9Z239}.;
Intolerance Scores
- LoFtool
- 0.393
- RVIS EVS
- 0.52
- RVIS percentile EVS
- 80.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.801