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. This gene product, FXYD5, is a glycoprotein that functions in the up-regulation of chemokine production, and it is involved in the reduction of cell adhesion via its ability to down-regulate E-cadherin. It also promotes metastasis, and has been linked to a variety of cancers. Alternative splicing results in multiple transcript variants. [RefSeq curation by Kathleen J. Sweadner, Ph.D., sweadner@helix.mgh.harvard.edu., Sep 2009]
Transcription factors with Perturb-seq knockdown data for FXYD5. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = FXYD5 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.
| TF | Mean coef | Binding | Outlier | TF→Gene link |
|---|
Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of FXYD5, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.
| Accessibility | Element | Dist. to TSS | Link type | TFs |
|---|---|---|---|---|
| chr19:34,920,040–34,921,057 | 234.2 kb | Distal (>10kb) Multiome | 309 | |
| chr19:34,926,731–34,927,343 | 227.8 kb | Distal (>10kb) Multiome | 741 | |
| chr19:34,963,909–34,964,414 | 190.5 kb | Distal (>10kb) Multiome | 645 | |
| chr19:34,999,304–35,000,970 | 154.5 kb | Distal (>10kb) Multiome | 759 | |
| chr19:35,030,124–35,031,270 | 124.2 kb | Distal (>10kb) Multiome | 534 | |
| chr19:35,040,969–35,041,953 | 113.1 kb | Distal (>10kb) Multiome | 806 | |
| chr19:35,055,754–35,056,570 | 98.7 kb | Distal (>10kb) Multiome | 268 | |
| chr19:35,066,952–35,067,448 | 87.5 kb | Distal (>10kb) Multiome | 497 | |
| chr19:35,067,923–35,068,779 | 86.0 kb | Distal (>10kb) Multiome | 190 | |
| chr19:35,090,562–35,091,150 | 63.9 kb | Distal (>10kb) Multiome | 303 | |
| chr19:35,135,242–35,135,695 | 19.2 kb | Distal (>10kb) Multiome | 525 | |
| chr19:35,140,763–35,141,948 | 13.4 kb | Distal (>10kb) Multiome | 509 | |
| chr19:35,142,085–35,143,541 | 11.7 kb | Distal (>10kb) Multiome | 328 | |
| chr19:35,153,816–35,154,015 | 713 bp | At TSS | 253 | |
| chr19:35,154,641–35,155,298 | 386 bp | At TSS Multiome | 552 | |
| chr19:35,247,580–35,249,688 | 94.0 kb | Distal (>10kb) Multiome | 1088 | |
| chr19:35,266,852–35,270,128 | 115.0 kb | Distal (>10kb) Multiome | 869 |
Genomic view of the FXYD5 locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.