SLC34A1

solute carrier family 34 member 1, the group of Solute carrier family 34

Basic information

Region (hg38): 5:177379234-177398848

Previous symbols: [ "NPT2", "SLC17A2" ]

Links

ENSG00000131183 ∙ NCBI:6569 ∙ OMIM:182309 ∙ HGNC:11019 ∙ Uniprot:Q06495 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the SLC34A1 gene.

• not provided (261 variants)
• Hypophosphatemic nephrolithiasis/osteoporosis 1 (65 variants)
• Inborn genetic diseases (28 variants)
• Hypercalcemia, infantile, 2 (23 variants)
• Fanconi renotubular syndrome 2;Hypophosphatemic nephrolithiasis/osteoporosis 1;Hypercalcemia, infantile, 2 (12 variants)
• SLC34A1-related condition (9 variants)
• Nephrolithiasis/osteoporosis, hypophosphatemic (9 variants)
• Fanconi renotubular syndrome 2 (9 variants)
• Factor XII deficiency disease (8 variants)
• Hereditary angioneurotic edema (8 variants)
• Hypophosphatemic nephrolithiasis/osteoporosis 1;Fanconi renotubular syndrome 2;Hypercalcemia, infantile, 2 (8 variants)
• Fanconi renotubular syndrome 2;Hypercalcemia, infantile, 2;Hypophosphatemic nephrolithiasis/osteoporosis 1 (8 variants)
• not specified (5 variants)
• Nephrocalcinosis;Nephrolithiasis (3 variants)
• Nephrocalcinosis (3 variants)
• Hypercalcemia, infantile, 2;Fanconi renotubular syndrome 2;Hypophosphatemic nephrolithiasis/osteoporosis 1 (3 variants)
• Hypophosphatemic nephrolithiasis/osteoporosis 1;Hypercalcemia, infantile, 2;Fanconi renotubular syndrome 2 (3 variants)
• Hypercalcemia, infantile, 2;Hypophosphatemic nephrolithiasis/osteoporosis 1;Fanconi renotubular syndrome 2 (3 variants)
• Neutropenia;Lymphopenia (1 variants)
• Autosomal recessive infantile hypercalcemia (1 variants)
• SLC34A1-Related Disorders (1 variants)
• Osteogenesis imperfecta type III (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			2	62	2	66
missense	1	3	110	8	2	124
nonsense	2	3	1			6
start loss						0
frameshift	6	4	4			14
inframe indel		1	4			5
splice donor/acceptor (+/-2bp)	1	3				4
splice region			9	6	1	16
non coding			18	28	16	62
Total	10	14	139	98	20

Highest pathogenic variant AF is 0.0000460

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			Uncertain significance (Aug 14, 2021)
5-177385797-G-A		Inborn genetic diseases • Hypophosphatemic nephrolithiasis/osteoporosis 1	Conflicting classifications of pathogenicity (Oct 16, 2023)
5-177385801-G-A			Likely benign (Dec 23, 2023)
5-177385813-G-T		Hypercalcemia, infantile, 2;Fanconi renotubular syndrome 2;Hypophosphatemic nephrolithiasis/osteoporosis 1	Uncertain significance (May 30, 2022)
5-177385814-C-T		Fanconi renotubular syndrome 2;Hypercalcemia, infantile, 2;Hypophosphatemic nephrolithiasis/osteoporosis 1	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 • Inborn genetic diseases • Hypophosphatemic nephrolithiasis/osteoporosis 1;Hypercalcemia, infantile, 2;Fanconi renotubular syndrome 2	Uncertain significance (Dec 01, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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