FXYD6
protein-codingFXYD domain containing ion transport regulator 6
Gene summary
This gene encodes a member of the FXYD family of transmembrane proteins. This particular protein encodes phosphohippolin, which likely affects the activity of Na,K-ATPase. Multiple alternatively spliced transcript variants encoding the same protein have been described. Related pseudogenes have been identified on chromosomes 10 and X. Read-through transcripts have been observed between this locus and the downstream sodium/potassium-transporting ATPase subunit gamma (FXYD2, GeneID 486) locus.[provided by RefSeq, Feb 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~40.5 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 FXYD6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022003.4. 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 | 1 | 1 | ||||
| missense | 5 | 5 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 6 | 0 | 0 | 6 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_071286.1 | 6 | MANE Select | |
| Ensembl | ENSP00000433312.1 | 6 | MANE Select | |
| RefSeq | NP_001158303.1 | 6 | Standard | |
| RefSeq | NP_001158304.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| fxyd6 | Danio rerio | Structure: ceratohyal cartilage Quality: deformed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ion channel transport
- Ion homeostasis
- Transport of small molecules
- Cardiac conduction
- Muscle contraction
Biological Process
- ion transport
- biological_process
- regulation of sodium ion transmembrane transporter activity
Molecular Function
- molecular_function
- protein binding
- sodium channel regulator activity
- ion channel regulator activity
Cellular Component
- plasma membrane
- glutamatergic synapse
- integral component of postsynaptic membrane
- integral component of presynaptic membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000526014
- Coding exons
- 6
- Length
- 40509
- Individuals with no LoFs
- 125673
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 125674
- p
- 0.00000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.778 | 36 | 51.7 | 0.696 | 0.00000277 | 613 |
| Missense (PolyPhen) | 10 | 19.292 | 0.51835 | 207 | ||
| Synonymous | -0.603 | 23 | 19.6 | 1.17 | 0.00000109 | 172 |
| Loss of Function | 2.16 | 1 | 7.31 | 0.137 | 3.09e-7 | 87 |
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) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.130
Intolerance Scores
- LoFtool
- 0.310
- RVIS EVS
- 0.24
- RVIS percentile EVS
- 68.72
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.539
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Low | Low | Low |
| Cancer | Low | Low | Low |