SLC17A4
protein-codingsolute carrier family 17 member 4, the group of Solute carrier family 17
Gene summary
Phosphate homeostasis is maintained by regulating intake, intestinal absorption, bone deposition and resorption, and renal excretion of phosphate. The central molecule in the control of phosphate excretion from the kidney is the sodium/phosphate cotransporter NPT1 (SLC17A1; MIM 182308), which is located in the renal proximal tubule. NPT1 uses the transmembrane electrochemical potential gradient of sodium to transport phosphate across the cell membrane. SLC17A4 is a similar sodium/phosphate cotransporter in the intestinal mucosa that plays an important role in the absorption of phosphate from the intestine (summary by Shibui et al., 1999 [PubMed 10319585]).[supplied by OMIM, 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 ~26.5 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 SLC17A4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005495.3. 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 | 1 | 1 | ||||
| missense | 64 | 5 | 69 | |||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 66 | 5 | 1 | 72 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005486.1 | 11 | MANE Select | |
| Ensembl | ENSP00000367137.4 | 11 | MANE Select | |
| RefSeq | NP_001273050.1 | 10 | Standard | |
| Ensembl | ENSP00000380266.2 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- phosphate-containing compound metabolic process
- sodium ion transport
- sialic acid transport
- sodium ion transmembrane transport
Molecular Function
- sodium:phosphate symporter activity
- sialic acid transmembrane transporter activity
Cellular Component
- lysosome
- integral component of plasma membrane
- membrane
- integral component of membrane
- apical plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000377905
- Coding exons
- 11
- Length
- 26493
- Individuals with no LoFs
- 123089
- Homozygous LoFs
- 30
- Heterozygous LoFs
- 2619
- Defined
- 125738
- p
- 0.0106
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0881 | 261 | 265 | 0.985 | 0.0000127 | 3199 |
| Missense (PolyPhen) | 71 | 84.033 | 0.84491 | 1104 | ||
| Synonymous | 0.127 | 97 | 98.6 | 0.984 | 0.00000500 | 1015 |
| Loss of Function | 1.27 | 17 | 23.6 | 0.719 | 0.00000109 | 280 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0025 | 0.0025 | notable |
| Latino/Admixed American | 0.0048 | 0.0048 | notable |
| Ashkenazi Jewish | 0.0058 | 0.0058 | notable |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.025 | 0.024 | notable |
| European (Non-Finnish) | 0.015 | 0.015 | notable |
| South Asian | 0.0033 | 0.0033 | notable |
| Other | 0.011 | 0.011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a membrane potential-dependent organic anion transporter, the transport requires a low concentration of chloride ions. May be involved in urate extrusion from the intestinal duct. May recognize hydrophilic anionic drugs such as aspirin, salicylate, and ibuprofen as substrates. Able to actively transport inorganic phosphate into cells via Na(+) cotransport (in vitro). {ECO:0000269|PubMed:22460716}.;
Recessive Scores
- pRec
- 0.135
Intolerance Scores
- LoFtool
- 0.908
- RVIS EVS
- 0.0000761
- RVIS percentile EVS
- 53.98
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.308
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |