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

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
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	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hypercalciuria	Likely pathogenic	rs1588844639	RCV001078193	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypophosphataemia or rickets	Likely pathogenic; Pathogenic	rs199690076	RCV006436691	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
SLC34A3-related disorder	Pathogenic; Likely pathogenic	rs121918238, rs199690076, rs765816079, rs757714479, rs369400414	RCV004745138 RCV003927693 RCV003419882 RCV004746281 RCV004746310	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypophosphatemic nephrolithiasis/osteoporosis 1	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOPHOSPHATEMIC RICKETS WITH HYPERCALCIURIA, HEREDITARY	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Kidney disorder	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEPHROLITHIASIS-OSTEOPOROSIS, HYPOPHOSPHATEMIC, 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adult Rickets	Rickets	HPO_DG			★☆☆☆☆ Found in Text Mining only
Barakat syndrome	Barakat syndrome	Pubtator	32155322	Associate	★☆☆☆☆ Found in Text Mining only
Bone Diseases	Bone disease	Pubtator	29809158	Associate	★☆☆☆☆ Found in Text Mining only
Bone Diseases Metabolic	Bone disease	Pubtator	39461557	Associate	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Familial Hypophosphatemic Rickets	Hypophosphatemic Rickets	LHGDN	18480181		★☆☆☆☆ Found in Text Mining only
Familial Hypophosphatemic Rickets	Hypophosphatemic Rickets	BEFREE	18523928, 19820004		★☆☆☆☆ Found in Text Mining only
Familial Hypophosphatemic Rickets	Hypophosphatemic rickets	Pubtator	18996815, 20074341, 29809158	Associate	★☆☆☆☆ Found in Text Mining only
Frontal bossing	Frontal bossing	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glycosuria Renal	Renal glycosuria	Pubtator	30798342	Associate	★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	29809158	Associate	★☆☆☆☆ Found in Text Mining only
Hereditary hypophosphatemic rickets with hypercalciuria	Hereditary Hypophosphatemic Rickets With Hypercalciuria	Orphanet			★☆☆☆☆ Found in Text Mining only
Hypercalcemia Infantile	Idiopathic infantile hypercalcemia	Pubtator	34125233	Associate	★☆☆☆☆ Found in Text Mining only
Hypercalciuria	Hypercalciuria	Pubtator	16358214, 18523928, 18996815, 19820004, 20074341, 22387237, 22806288, 29809158, 32155322, 32311027, 39461557	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypercalciuria Absorptive 2	Hypercalciuria	Pubtator	22387237	Associate	★☆☆☆☆ Found in Text Mining only
Hyperphosphatemia (disorder)	Hyperphosphatemia	BEFREE	29993278		★☆☆☆☆ Found in Text Mining only
Hypophosphatemic Rickets	Hypophosphatemic Rickets	BEFREE	18523928, 19820004		★☆☆☆☆ Found in Text Mining only
Hypophosphatemic Rickets	Hypophosphatemic Rickets	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypophosphatemic Rickets Autosomal Dominant	Hypophosphatemic rickets	Pubtator	32311027	Associate	★☆☆☆☆ Found in Text Mining only
Hypophosphatemic Rickets with Hypercalciuria Hereditary	Hypophosphatemic rickets	Pubtator	16358214, 18523928, 19820004, 20074341, 21344632, 22387237, 22672866, 22806288, 23246670, 24176905, 27939817, 29809158, 30798342, 32311027, 35689455, 38364990	Associate	★☆☆☆☆ Found in Text Mining only
HYPOPHOSPHATEMIC RICKETS WITH HYPERCALCIURIA, HEREDITARY	HYPOPHOSPHATEMIC RICKETS WITH HYPERCALCIURIA, HEREDITARY	BEFREE	16358214, 16358215, 16849419, 18480181, 18996815, 22672866, 23246670, 24176905, 24246249, 30317447		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOPHOSPHATEMIC RICKETS WITH HYPERCALCIURIA, HEREDITARY	HYPOPHOSPHATEMIC RICKETS WITH HYPERCALCIURIA, HEREDITARY	UNIPROT_DG	16358214, 16358215		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOPHOSPHATEMIC RICKETS WITH HYPERCALCIURIA, HEREDITARY	HYPOPHOSPHATEMIC RICKETS WITH HYPERCALCIURIA, HEREDITARY	ORPHANET_DG	16358215		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOPHOSPHATEMIC RICKETS WITH HYPERCALCIURIA, HEREDITARY	HYPOPHOSPHATEMIC RICKETS WITH HYPERCALCIURIA, HEREDITARY	GENOMICS_ENGLAND_DG	16849419, 24700880		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOPHOSPHATEMIC RICKETS WITH HYPERCALCIURIA, HEREDITARY	HYPOPHOSPHATEMIC RICKETS WITH HYPERCALCIURIA, HEREDITARY	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOPHOSPHATEMIC RICKETS WITH HYPERCALCIURIA, HEREDITARY	HYPOPHOSPHATEMIC RICKETS WITH HYPERCALCIURIA, HEREDITARY	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypophosphatemic Rickets, X-Linked Dominant	Hypophosphatemic Rickets	BEFREE	18775977		★☆☆☆☆ Found in Text Mining only
Kidney Calculi	Kidney stone	BEFREE	17872384, 18446382, 18480181, 19820004, 21344632, 22387237, 24700880, 27784695, 28448530, 28704395, 29275531, 30109410, 30798342		★☆☆☆☆ Found in Text Mining only
Kidney Diseases	Kidney disease	Pubtator	34721296	Associate	★☆☆☆☆ Found in Text Mining only
Medullary nephrocalcinosis	Medullary nephrocalcinosis	BEFREE	24700880		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic syndrome	Pubtator	18996815	Associate	★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	19820004		★☆☆☆☆ Found in Text Mining only
Nephrocalcinosis	Nephrocalcinosis	BEFREE	22387237, 24700880, 27784695, 28448530, 28704395, 30109410, 31789978		★☆☆☆☆ Found in Text Mining only
Nephrolithiasis	Nephrolithiasis	BEFREE	17872384, 18446382, 18480181, 19820004, 21344632, 22387237, 24700880, 28448530, 29275531, 30109410, 30798342		★☆☆☆☆ Found in Text Mining only
Nephrolithiasis	Nephrolithiasis	Pubtator	18996815, 19820004, 21344632, 27939817	Associate	★☆☆☆☆ Found in Text Mining only
Osteomalacia	Osteomalacia	Pubtator	22387237, 39461557	Associate	★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	Pubtator	29809158, 39461557	Associate	★☆☆☆☆ Found in Text Mining only
Phosphate Diabetes	Phosphate Diabetes	BEFREE	18775977		★☆☆☆☆ Found in Text Mining only
Renal tubular disorder	Renal Tubular Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
Rickets	Rickets	BEFREE	17872384, 18446382, 30317447		★☆☆☆☆ Found in Text Mining only
Rickets	Rickets	Pubtator	22387237, 23246670, 39461557	Associate	★☆☆☆☆ Found in Text Mining only
Rickets	Rickets	HPO_DG			★☆☆☆☆ Found in Text Mining only
Rickets Hypophosphatemic	Hypophosphatemic rickets	Pubtator	18523928, 22695891, 26107949, 32155322, 32311027	Associate	★☆☆☆☆ Found in Text Mining only
Vitamin D Deficiency	Vitamin d deficiency	Pubtator	18523928, 29809158	Associate	★☆☆☆☆ Found in Text Mining only
Vitamin D-Resistant Rickets, X-Linked	Vitamin D-Dependent Rickets	BEFREE	29505567		★☆☆☆☆ Found in Text Mining only