SLC34A3 (solute carrier family 34 member 3)

Gene

• Entrez ID: 142680
• Gene name: Solute carrier family 34 member 3
• Gene symbol: SLC34A3
• Synonyms (NCBI Gene): HHRH, NPT2C, NPTIIc
• Chromosome: 9
• Chromosome location: 9q34.3
• Summary: This gene encodes a member of SLC34A transporter family of proteins, and is expressed primarily in the kidney. It is involved in transporting phosphate into cells via sodium cotransport in the renal brush border membrane, and contributes to the maintenanc

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121918234	G>A,C,T	Pathogenic	Coding sequence variant, missense variant
rs121918235	C>A,T	Pathogenic	Coding sequence variant, missense variant
rs121918236	G>A	Pathogenic	Coding sequence variant, synonymous variant
rs121918237	G>A,T	Pathogenic	Coding sequence variant, missense variant
rs121918238	C>A,T	Pathogenic	Genic downstream transcript variant, downstream transcript variant, synonymous variant, stop gained, coding sequence variant, missense variant
rs121918239	G>A,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant, missense variant
rs140869490	G>C	Conflicting-interpretations-of-pathogenicity	3 prime UTR variant, genic downstream transcript variant, downstream transcript variant, coding sequence variant, missense variant
rs144666114	T>C	Conflicting-interpretations-of-pathogenicity	3 prime UTR variant, downstream transcript variant, genic downstream transcript variant, synonymous variant, coding sequence variant
rs146097023	G>A	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs150841256	G>A	Likely-pathogenic, pathogenic-likely-pathogenic	Splice donor variant
rs199536442	C>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs199690076	C>G,T	Pathogenic	Missense variant, coding sequence variant
rs201293634	T>C	Pathogenic	Splice donor variant
rs746082077	TGGGGCTGCAGTGGCAGCCCCAGCCCGGGC>-	Likely-pathogenic	Intron variant
rs762610288	G>A	Likely-pathogenic	Coding sequence variant, genic downstream transcript variant, downstream transcript variant, stop gained
rs765816079	->C	Pathogenic, likely-pathogenic	Coding sequence variant, genic downstream transcript variant, frameshift variant, downstream transcript variant
rs768893184	G>A	Likely-pathogenic	Intron variant
rs777986863	C>G	Likely-pathogenic	Genic downstream transcript variant, coding sequence variant, missense variant, downstream transcript variant, stop gained
rs794729658	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs794729659	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs886044633	C>T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs1060499697	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1064796402	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1064796955	G>A	Likely-pathogenic	Coding sequence variant, genic downstream transcript variant, downstream transcript variant, stop gained
rs1554784044	AAGCCCCCTACACCCCCCACACTCCCCCTCACCGGCCCCTACATGGAGAGGAACAGCACAGCCCCGGCGGACAGGCTGCCCTGTGAGGCCCGGCCCACCCC>-	Pathogenic	Coding sequence variant, splice donor variant, intron variant
rs1554784508	AGCATCCCCCATAGACTTCCCCTTCCCACCAGGCTGACTCGGGGGCTACCTGGCCCTCCTTGTGGGCGCTGGCCAGGGCTGACCC>-	Pathogenic	Intron variant
rs1554785333	->G	Pathogenic	Frameshift variant, genic downstream transcript variant, coding sequence variant, downstream transcript variant
rs1554785389	CGCTCCTGGGCCTG>-	Pathogenic	Frameshift variant, genic downstream transcript variant, coding sequence variant, downstream transcript variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005436	Function	Sodium:phosphate symporter activity	IBA
GO:0005436	Function	Sodium:phosphate symporter activity	IDA	11880379
GO:0005436	Function	Sodium:phosphate symporter activity	IEA
GO:0005436	Function	Sodium:phosphate symporter activity	TAS
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0005903	Component	Brush border	IBA
GO:0005903	Component	Brush border	IEA
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006814	Process	Sodium ion transport	IDA	11880379
GO:0006814	Process	Sodium ion transport	IEA
GO:0006817	Process	Phosphate ion transport	IDA	11880379
GO:0006817	Process	Phosphate ion transport	IEA
GO:0015293	Function	Symporter activity	IEA
GO:0016020	Component	Membrane	IEA
GO:0016324	Component	Apical plasma membrane	IBA
GO:0016324	Component	Apical plasma membrane	IEA
GO:0016324	Component	Apical plasma membrane	ISS	11880379
GO:0030643	Process	Intracellular phosphate ion homeostasis	IBA
GO:0030643	Process	Intracellular phosphate ion homeostasis	IDA	16358214
GO:0031526	Component	Brush border membrane	IEA
GO:0031526	Component	Brush border membrane	ISS
GO:0031982	Component	Vesicle	IBA
GO:0035725	Process	Sodium ion transmembrane transport	IEA
GO:0044341	Process	Sodium-dependent phosphate transport	IBA
GO:0044341	Process	Sodium-dependent phosphate transport	IEA
GO:0055085	Process	Transmembrane transport	IEA

Other IDs

• MIM: 609826
• HGNC: 20305
• e!Ensembl: ENSG00000198569

Protein

• UniProt ID: Q8N130
• Protein name: Sodium-dependent phosphate transport protein 2C (Sodium-phosphate transport protein 2C) (Na(+)-dependent phosphate cotransporter 2C) (Sodium/inorganic phosphate cotransporter IIC) (Sodium/phosphate cotransporter 2C) (Na(+)/Pi cotransporter 2C) (NaPi-2c) (
• Protein function: Involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane (PubMed:11880379). The cotransport has a Na(+):Pi stoichiometry of 2:1 and is electroneutral (By similarity). {ECO:0000250|UniProtKB:
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02690	Na_Pi_cotrans	85 → 230	Na+/Pi-cotransporter	Family
  PF02690	Na_Pi_cotrans	333 → 529	Na+/Pi-cotransporter	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed only in the kidney. {ECO:0000269|PubMed:11880379}.
• Sequence:

  MPSSLPGSQVPHPTLDAVDLVEKTLRNEGTSSSAPVLEEGDTDPWTLPQLKDTSQPWKEL
  RVAGRLRRVAGSVLKACGLLGSLYFFICSLDVLSSAFQLLGSKVAGDIFKDNVVLSNPVA
  GLVIGVLVTALVQSSSTSSSIVVSMVAAKLLTVRVSVPIIMGVNVGTSITSTLVSMAQSG
  DRDEFQRAFSGSAVHGIFNWLTVLVLLPLESATALLERLSELALGAASLTPRAQAPDILK
  VLTKPLTHLIVQLDSDMIMSSATGNATNSSLIKHWCGTTGQPTQENSSCGAFGPCTEKNS
  TAPADRLPCRHLFAGTELTDLAVGCILLAGSLLVLCGCLVLIVKLLNSVLRGRVAQVVRT
  VINADFPFPLGWLGGYLAVLAGAGLTFALQSSSVFTAAVVPLMGVGVISLDRAYPLLLGS
  NIGTTTTALLAALASPADRMLSALQVALIHFFFNLAGILLWYLVPALRLPIPLARHFGVV
  TARYRWVAGVYLLLGFLLLPLAAFGLSLAGGMELAAVGGPLVGLVLLVILVTVLQRRRPA
  WLPVRLRSWAWLPVWLHSLEPWDRLVTRCCPCNVCSPPKATTKEAYCYENPEILASQQL

• Sequence length: 599

Pathways

KEGG:

Parathyroid hormone synthesis, secretion and action
Mineral absorption

Reactome:

Type II Na+/Pi cotransporters
Defective SLC34A3 causes Hereditary hypophosphatemic rickets with hypercalciuria (HHRH)

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Autosomal recessive hypophosphatemic bone disease	Likely pathogenic; Pathogenic	rs1473192539, rs750178720, rs754054340, rs752222200, rs755196320, rs949841477, rs2131423939, rs2131415051, rs1345816189, rs794729658, rs121918235, rs794729659, rs121918237, rs121918238, rs1554784044, rs1554784508, rs139408872, rs770803386, rs199690076, rs1169054324, rs1836451628, rs781602446, rs748739254, rs2538815347, rs1158991453, rs1017086601, rs1060499697, rs762610288, rs1554785333, rs201293634, rs765816079, rs1554785389, rs150841256, rs759768852, rs777986863, rs1836579405, rs757714479, rs369400414	RCV005049013 RCV002484811 RCV002504626 RCV002285027 RCV001535840 RCV001536036 RCV001806330 RCV004785386 RCV002482406 RCV000001491 RCV000001493 RCV000001495 RCV000001496 RCV000001497 RCV000001498 RCV000001500 RCV002246721 RCV005051256 RCV000513414 RCV005050607 RCV005050644 RCV003388712 RCV005040606 RCV004556894 RCV004579649 RCV004594802 RCV000449572 RCV002475946 RCV000505556 RCV000513447 RCV000513261 RCV000513018 RCV000513307 RCV000681630 RCV000625609 RCV001029881 RCV005047268 RCV002290646 RCV005040159
Hypercalciuria	Likely pathogenic	rs1588844639	RCV001078193
Hypophosphataemia or rickets	Likely pathogenic; Pathogenic	rs199690076	RCV006436691
SLC34A3-related disorder	Pathogenic; Likely pathogenic	rs121918238, rs199690076, rs765816079, rs757714479, rs369400414	RCV004745138 RCV003927693 RCV003419882 RCV004746281 RCV004746310

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Cervical cancer	Benign	rs35699762	RCV005889714
Clear cell carcinoma of kidney	Conflicting classifications of pathogenicity; Benign	rs121918239, rs35699762	RCV005887191 RCV005889715
Familial cancer of breast	Uncertain significance	rs200186549	RCV005897261
Hypophosphatemic nephrolithiasis/osteoporosis 1	Conflicting classifications of pathogenicity	rs200536604	RCV002253785
Kidney disorder	Conflicting classifications of pathogenicity	rs141734934, rs776275610	RCV005622079 RCV005622078
Thyroid cancer, nonmedullary, 1	Conflicting classifications of pathogenicity; Benign	rs121918239, rs35699762	RCV005887192 RCV005889716

Associations from Text Mining
Disease Name	Relationship Type	References
Barakat syndrome	Associate	32155322
Bone Diseases	Associate	29809158
Bone Diseases Metabolic	Associate	39461557
Congenital Hereditary and Neonatal Diseases and Abnormalities	Associate	30798342
Familial Hypophosphatemic Rickets	Associate	18996815, 20074341, 29809158
Femoral Fractures	Associate	18996815
Flank Pain	Associate	18996815
Fractures Multiple	Associate	27939817
Genetic Diseases Inborn	Associate	37414395
Glycosuria Renal	Associate	30798342
Growth Disorders	Associate	29809158
Hypercalcemia Infantile	Associate	34125233
Hypercalciuria	Associate	16358214, 18523928, 18996815, 19820004, 20074341, 22387237, 22806288, 29809158, 32155322, 32311027, 39461557
Hypercalciuria Absorptive 2	Associate	22387237
Hypophosphatemia	Associate	22387237, 34721296, 37432176, 39461557
Hypophosphatemia Renal with Intracerebral Calcifications	Associate	18523928, 30798342
Hypophosphatemic Rickets Autosomal Dominant	Associate	32311027
Hypophosphatemic Rickets with Hypercalciuria Hereditary	Associate	16358214, 18523928, 19820004, 20074341, 21344632, 22387237, 22672866, 22806288, 23246670, 24176905, 27939817, 29809158, 30798342, 32311027, 35689455, 38364990
Kidney Calculi	Associate	22387237, 29809158, 30798342, 32155322, 37432176, 39461557
Kidney Diseases	Associate	34721296
Lithiasis	Associate	34721296
Metabolic Diseases	Associate	18996815
Myotonia with Skeletal Abnormalities and Mental Retardation	Associate	35689455
Neoplastic Syndromes Hereditary	Associate	29505567
Nephrocalcinosis	Associate	18523928, 20074341, 22387237, 30798342, 34721296, 35689455, 39461557
Nephrolithiasis	Associate	18996815, 19820004, 21344632, 27939817
Nephrolithiasis Osteoporosis Hypophosphatemic 1	Associate	32311027
Osteomalacia	Associate	22387237, 39461557
Osteoporosis	Associate	29809158, 39461557
Rare Diseases	Associate	26789268
Renal Insufficiency Chronic	Associate	39461557
Rickets	Associate	22387237, 23246670, 39461557
Rickets Hypophosphatemic	Associate	18523928, 22695891, 26107949, 32155322, 32311027
Urinary Calculi	Associate	37414395
Vitamin D Deficiency	Associate	18523928, 29809158
Wasting Syndrome	Associate	22387237, 30798342, 32311027, 34721296, 39461557