SLC34A1
solute carrier family 34 member 1, the group of Solute carrier family 34
Basic information
Region (hg38): 5:177379235-177398848
Previous symbols: [ "NPT2", "SLC17A2" ]
Links
Phenotypes
GenCC
Source:
- primary Fanconi syndrome (Supportive), mode of inheritance: AD
- dominant hypophosphatemia with nephrolithiasis or osteoporosis (Supportive), mode of inheritance: AD
- autosomal recessive infantile hypercalcemia (Supportive), mode of inheritance: AR
- Fanconi renotubular syndrome 2 (Limited), mode of inheritance: AR
- hypercalcemia, infantile, 2 (Moderate), mode of inheritance: AR
- hypophosphatemic nephrolithiasis/osteoporosis 1 (Limited), mode of inheritance: AD
- hypercalcemia, infantile, 2 (Strong), mode of inheritance: AR
- hypophosphatemic nephrolithiasis/osteoporosis 1 (Limited), mode of inheritance: AD
- hypercalcemia, infantile, 2 (Definitive), mode of inheritance: AR
- Fanconi renotubular syndrome 2 (Disputed Evidence), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Fanconi renotubular syndrome 2; Hypercalcemia, infantile 2; Nephrolithiasis/osteoporosis, hypophosphatemic, 1 | AR | Renal | In Fanconi renotubular syndrome 4, treatment with neutral phosphate has been reported as resulting in improvement in some but not all clinical, radiological, and laboratory parameters; Due to increased renal phosphate loss, individuals may be at increased risk of renal stone formation and/or bone demineralization; In Hypercalcemia, infantile 2, chronic (with vitamin D supplements) and acute (including IV rehydration, furosemide, corticosteroids, ketoconazole, and oral phosphate) medical management has been described as beneficial in many individuals | Renal | 2842681; 12324554; 20335586; 26047794 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (10 variants)
- Hypercalcemia, infantile, 2 (3 variants)
- Hypophosphatemic nephrolithiasis/osteoporosis 1 (2 variants)
- Nephrocalcinosis;Nephrolithiasis (1 variants)
- SLC34A1-related disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC34A1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 74 | 78 | ||||
| missense | 122 | 137 | ||||
| nonsense | 7 | |||||
| start loss | 0 | |||||
| frameshift | 15 | |||||
| inframe indel | 5 | |||||
| splice donor/acceptor (+/-2bp) | 8 | |||||
| splice region | 9 | 10 | 1 | 20 | ||
| non coding | 19 | 42 | 16 | 77 | ||
| Total | 12 | 17 | 153 | 125 | 20 |
Highest pathogenic variant AF is 0.00216
Variants in SLC34A1
This is a list of pathogenic ClinVar variants found in the SLC34A1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-177384467-G-A | Hypophosphatemic nephrolithiasis/osteoporosis 1 | Uncertain significance (Jan 13, 2018) | ||
| 5-177384483-C-A | Uncertain significance (Jun 10, 2021) | |||
| 5-177384487-G-C | Hypophosphatemic nephrolithiasis/osteoporosis 1 | Uncertain significance (Jan 12, 2018) | ||
| 5-177385731-G-C | Hypophosphatemic nephrolithiasis/osteoporosis 1 | Benign (Jan 13, 2018) | ||
| 5-177385741-G-A | not specified | Uncertain significance (Feb 01, 2024) | ||
| 5-177385753-C-T | Likely benign (May 30, 2022) | |||
| 5-177385754-G-A | Malignant tumor of prostate | Uncertain significance (-) | ||
| 5-177385759-G-A | Likely benign (Sep 12, 2022) | |||
| 5-177385762-G-C | Uncertain significance (Feb 28, 2022) | |||
| 5-177385764-T-C | Inborn genetic diseases | Uncertain significance (Jan 04, 2024) | ||
| 5-177385766-G-T | Hypophosphatemic nephrolithiasis/osteoporosis 1 • Inborn genetic diseases | Conflicting classifications of pathogenicity (Jan 09, 2024) | ||
| 5-177385773-CT-GG | Uncertain significance (Apr 19, 2022) | |||
| 5-177385785-C-G | Inborn genetic diseases | Uncertain significance (Oct 26, 2022) | ||
| 5-177385787-C-T | Uncertain significance (Mar 29, 2022) | |||
| 5-177385796-C-T | Inborn genetic diseases | Uncertain significance (Jun 13, 2024) | ||
| 5-177385797-G-A | Hypophosphatemic nephrolithiasis/osteoporosis 1 • Inborn genetic diseases | Conflicting classifications of pathogenicity (Oct 16, 2023) | ||
| 5-177385801-G-A | Likely benign (Dec 23, 2023) | |||
| 5-177385813-G-T | Hypophosphatemic nephrolithiasis/osteoporosis 1;Fanconi renotubular syndrome 2;Hypercalcemia, infantile, 2 | Uncertain significance (May 30, 2022) | ||
| 5-177385814-C-T | Fanconi renotubular syndrome 2;Hypophosphatemic nephrolithiasis/osteoporosis 1;Hypercalcemia, infantile, 2 | Pathogenic/Likely pathogenic (Dec 21, 2023) | ||
| 5-177385815-G-A | Hypophosphatemic nephrolithiasis/osteoporosis 1 | Conflicting classifications of pathogenicity (Jan 16, 2023) | ||
| 5-177385821-C-T | Uncertain significance (Jul 26, 2022) | |||
| 5-177385822-G-A | Likely benign (Oct 04, 2023) | |||
| 5-177385823-GC-TT | Uncertain significance (Jan 28, 2022) | |||
| 5-177385834-C-T | Likely benign (Jul 23, 2022) | |||
| 5-177385835-G-A | Hypophosphatemic nephrolithiasis/osteoporosis 1 • Hypercalcemia, infantile, 2;Fanconi renotubular syndrome 2;Hypophosphatemic nephrolithiasis/osteoporosis 1 • Inborn genetic diseases | Uncertain significance (Dec 01, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SLC34A1 | protein_coding | protein_coding | ENST00000324417 | 12 | 19614 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 8.91e-27 | 0.00000422 | 125570 | 0 | 178 | 125748 | 0.000708 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.475 | 400 | 374 | 1.07 | 0.0000232 | 4078 |
| Missense in Polyphen | 126 | 109.08 | 1.1551 | 1233 | ||
| Synonymous | -0.240 | 170 | 166 | 1.02 | 0.0000109 | 1441 |
| Loss of Function | -1.85 | 34 | 24.2 | 1.41 | 0.00000122 | 259 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000851 | 0.000843 |
| Ashkenazi Jewish | 0.0000994 | 0.0000992 |
| East Asian | 0.00125 | 0.00125 |
| Finnish | 0.000151 | 0.000139 |
| European (Non-Finnish) | 0.000733 | 0.000721 |
| Middle Eastern | 0.00125 | 0.00125 |
| South Asian | 0.00154 | 0.00154 |
| Other | 0.000489 | 0.000489 |
dbNSFP
Source:
- Function
- FUNCTION: Involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane. Probably mediates 70-80% of the apical influx. {ECO:0000269|PubMed:26047794, ECO:0000269|PubMed:8327470}.;
- Disease
- DISEASE: Fanconi renotubular syndrome 2 (FRTS2) [MIM:613388]: A disease due to a generalized dysfunction of the proximal kidney tubule resulting in decreased solute and water reabsorption. Patients have polydipsia and polyuria with phosphaturia, glycosuria and aminoaciduria. They may develop hypophosphatemic rickets or osteomalacia, acidosis and a tendency toward dehydration. Some eventually develop renal insufficiency. {ECO:0000269|PubMed:20335586}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hypercalcemia, infantile, 2 (HCINF2) [MIM:616963]: An autosomal recessive form of hypercalcemia, a disorder characterized by abnormally high level of calcium in the blood, failure to thrive, vomiting, dehydration, and nephrocalcinosis. {ECO:0000269|PubMed:26047794}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Surfactant metabolism;Metabolism of proteins;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;Type II Na+/Pi cotransporters;Sodium-coupled phosphate cotransporters
(Consensus)
Recessive Scores
- pRec
- 0.288
Intolerance Scores
- loftool
- 0.363
- rvis_EVS
- -0.8
- rvis_percentile_EVS
- 12.53
Haploinsufficiency Scores
- pHI
- 0.226
- hipred
- Y
- hipred_score
- 0.564
- ghis
- 0.487
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.108
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Slc34a1
- Phenotype
- behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; skeleton phenotype; renal/urinary system phenotype; growth/size/body region phenotype; muscle phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- ossification;kidney development;phosphate ion transport;glycoprotein metabolic process;response to lead ion;cellular phosphate ion homeostasis;response to magnesium ion;response to estradiol;response to vitamin A;phosphate ion transmembrane transport;response to potassium ion;indole metabolic process;response to drug;cellular protein metabolic process;sodium-dependent phosphate transport;positive regulation of membrane potential;response to cadmium ion;response to mercury ion;protein homooligomerization;phosphate ion homeostasis;response to growth hormone;cellular response to metal ion;cellular response to parathyroid hormone stimulus;tricarboxylic acid metabolic process;cellular response to staurosporine;response to thyroid hormone;dentinogenesis;sodium ion import across plasma membrane;gentamycin metabolic process;arsenate ion transmembrane transport;positive regulation of sodium-dependent phosphate transport;positive regulation of phosphate transmembrane transport
- Cellular component
- endosome;plasma membrane;integral component of plasma membrane;brush border;cell surface;apical plasma membrane;nuclear speck;brush border membrane;vesicle;membrane raft;perinuclear region of cytoplasm;mitotic spindle
- Molecular function
- sodium:phosphate symporter activity;protein binding;sodium-dependent phosphate transmembrane transporter activity;PDZ domain binding;protein homodimerization activity;protein-containing complex binding