SLC34A3

Summary

SLC34A3 (solute carrier family 34 member 3, HGNC:20305) is a protein-coding gene on chromosome 9q34.3, encoding Sodium-dependent phosphate transport protein 2C (Q8N130). Involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane.

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 maintenance of inorganic phosphate concentration in the kidney. Mutations in this gene are associated with hereditary hypophosphatemic rickets with hypercalciuria. Alternatively spliced transcript variants varying in the 5’ UTR have been found for this gene.

Source: NCBI Gene 142680 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary hypophosphatemic rickets with hypercalciuria (Definitive, GenCC)
• Clinical variants (ClinVar): 866 total — 34 pathogenic, 44 likely-pathogenic
• Phenotypes (HPO): 52
• Druggable target: yes
• MANE Select transcript: NM_001177316

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20305
Approved symbol	SLC34A3
Name	solute carrier family 34 member 3
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	NPTIIc, FLJ38680, NaPi-2c, NPT2C
Ensembl gene	ENSG00000198569
Ensembl biotype	protein_coding
OMIM	609826
Entrez	142680

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000361134, ENST00000538474, ENST00000673835, ENST00000673865, ENST00000673953

RefSeq mRNA: 3 — MANE Select: NM_001177316 NM_001177316, NM_001177317, NM_080877

CCDS: CCDS7038

Canonical transcript exons

ENST00000673835 — 13 exons

Exon	Start	End
ENSE00001403803	137232784	137232927
ENSE00001403951	137234416	137234532
ENSE00001408623	137234607	137234731
ENSE00001408901	137231664	137231787
ENSE00001411565	137232072	137232161
ENSE00001413938	137233863	137233941
ENSE00001416250	137234109	137234276
ENSE00001421850	137233209	137233404
ENSE00001425058	137233004	137233115
ENSE00001426060	137233633	137233722
ENSE00001432951	137232575	137232703
ENSE00003897277	137230901	137230938
ENSE00003897676	137235952	137236555

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 83.51.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0057 / max 7.3709, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99677	0.0057	3

Top tissues by expression

240 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	83.51	gold quality
right uterine tube	UBERON:0001302	81.64	gold quality
adult mammalian kidney	UBERON:0000082	76.01	gold quality
sural nerve	UBERON:0015488	72.39	gold quality
pituitary gland	UBERON:0000007	72.32	gold quality
adenohypophysis	UBERON:0002196	72.27	gold quality
kidney	UBERON:0002113	71.08	gold quality
upper leg skin	UBERON:0004262	69.82	silver quality
esophagus mucosa	UBERON:0002469	68.67	gold quality
endothelial cell	CL:0000115	68.31	silver quality
skin of hip	UBERON:0001554	67.49	silver quality
metanephros cortex	UBERON:0010533	66.12	gold quality
cortex of kidney	UBERON:0001225	65.96	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	64.53	gold quality
small intestine Peyer’s patch	UBERON:0003454	62.67	gold quality
esophagus	UBERON:0001043	62.33	gold quality
small intestine	UBERON:0002108	61.41	gold quality
mucosa of stomach	UBERON:0001199	61.36	gold quality
amniotic fluid	UBERON:0000173	60.47	gold quality
right frontal lobe	UBERON:0002810	60.06	gold quality
buccal mucosa cell	CL:0002336	59.63	gold quality
right lung	UBERON:0002167	58.92	gold quality
ventricular zone	UBERON:0003053	58.80	gold quality
minor salivary gland	UBERON:0001830	58.63	gold quality
metanephros	UBERON:0000081	58.50	gold quality
body of stomach	UBERON:0001161	58.47	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	57.91	gold quality
left lobe of thyroid gland	UBERON:0001120	57.71	gold quality
thyroid gland	UBERON:0002046	57.10	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	56.97	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.14

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RARA

miRNA regulators (miRDB)

4 targeting SLC34A3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-3665	97.73	65.08	975

Literature-anchored findings (GeneRIF, showing 21)

• Functionally important sites in the predicted first and fourth extracellular linkers of the type IIa Na+/Pi cotransporter (NaPi-IIa) were identified by cysteine scanning mutagenesis (Ehnes et al., 2004). (PMID:15504899)
• NaP(i)-IIc has a key role in the regulation of phosphate homeostasis. (PMID:16358214)
• Loss of function of the SLC34A3 protein presumably results in a primary renal tubular defect and is compatible with the hereditary hypophosphatemic rickets with hypercalciuria phenotype. (PMID:16358215)
• Therefore, understanding the mechanisms that control the apical expression of NaPi-IIa and NaPi-IIc as well as their functional properties is critical to understanding how an organism achieves P i homeostasis. (PMID:16955105)
• Hereditary hypophosphatemic rickets with hypercalciuria were speculated to be associated with the abnormal functions of phosphate transporter gene type IIc. (PMID:17968493)
• A novel missense mutation in SLC34A3 causes hereditary hypophosphatemic rickets with hypercalciuria in humans. (PMID:18480181)
• Novel mutation in the SLC34A3 gene in a patient with an unusual presentation of hereditary hypophosphatemic rickets with hypercalciuria. (PMID:19820004)
• these data suggest that mutations in SLC34A3 in hereditary hypophosphatemic rickets with hypercalciuria result in defective processing and stability (PMID:22159077)
• SLC34A3 mutations (exons and introns) were searched in two previously not reported hereditary hypophosphatemic rickets with hypercalciuria kindreds, which resulted in the identification of three novel mutations. (PMID:22387237)
• Data show 101-bp deletion in intron 9 of the SLC34A3 gene. (PMID:22672866)
• A man with hereditary hypophosphataemic rickets with hypercalciuria & his 3 heterozygous children had a mutation in intron 5 of gene SLC34A3 (NM_080877.2:c[ 448 +5G>A] + [ 448 +5G>A]). (PMID:22806288)
• this study reports the first cases of hereditary hypophosphatemic rickets with hypercalciuria in Africa and describes a novel causal mutation within the SLC34A3 gene (PMID:23246670)
• Individuals with mutations affecting both SLC34A3 alleles had a significantly increased risk of kidney stone formation or medullary nephrocalcinosis, namely 46% compared with 6% observed in healthy family members carrying only the wild-type allele. (PMID:24700880)
• This is the report of a patient with compound heterozygous mutations of SLC34A3 and normal skeletal features. Biallelic mutations in SLC34A3 can thus be associated with hypercalciuria not accompanied by rickets. (PMID:24924704)
• genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3 (PMID:29505567)
• Of the twelve family members three were homozygote and seven heterozygote for the same solute carrier family 34 (sodium phosphate), member 3 protein (SLC34A3) variant. (PMID:29809158)
• Novel heterozygous GATA3 and SLC34A3 variants in a 6-year-old boy with Barakat syndrome and hypercalciuria. (PMID:32155322)
• Digenic Heterozygous Mutations in SLC34A3 and SLC34A1 Cause Dominant Hypophosphatemic Rickets with Hypercalciuria. (PMID:32311027)
• The genetic polymorphisms of XPR1 and SCL34A3 are associated with Fanconi syndrome in Chinese patients of tumor-induced osteomalacia. (PMID:32725396)
• Relationship between clinical phenotype and in vitro analysis of 13 NPT2c/SCL34A3 mutants. (PMID:36596813)
• Rare variants in the sodium-dependent phosphate transporter gene SLC34A3 explain missing heritability of urinary stone disease. (PMID:37414395)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Slc34a3	ENSMUSG00000006469
rattus_norvegicus	Slc34a3	ENSRNOG00000010451
caenorhabditis_elegans		WBGENE00022767

Paralogs (2): SLC34A1 (ENSG00000131183), SLC34A2 (ENSG00000157765)

Protein

Protein identifiers

Sodium-dependent phosphate transport protein 2C — Q8N130 (reviewed: Q8N130)

Alternative names: Na(+)-dependent phosphate cotransporter 2C, Sodium/inorganic phosphate cotransporter IIC, Sodium/phosphate cotransporter 2C, Solute carrier family 34 member 3

All UniProt accessions (3): A0A669KB46, A0A669KB63, Q8N130

UniProt curated annotations — full annotation on UniProt →

Function. Involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane. The cotransport has a Na(+):Pi stoichiometry of 2:1 and is electroneutral.

Subcellular location. Apical cell membrane.

Tissue specificity. Expressed only in the kidney.

Disease relevance. Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) [MIM:241530] Autosomal recessive form of hypophosphatemia characterized by reduced renal phosphate reabsorption and rickets. Increased serum levels of 1,25-dihydroxyvitamin D lead to increase in urinary calcium excretion. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the SLC34A transporter family.

RefSeq proteins (3): NP_001170787, NP_001170788, NP_543153 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003841	Na/Pi_transpt	Family

Pfam: PF02690

Catalyzed reactions (Rhea), 1 shown:

• 2 Na(+)(out) + phosphate(out) = 2 Na(+)(in) + phosphate(in) (RHEA:71259)

UniProt features (35 total): sequence variant 11, topological domain 9, transmembrane region 8, glycosylation site 4, chain 1, modified residue 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N130-F1	75.86	0.28

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 4

Disulfide bonds (1): 276–309

Glycosylation sites (4): 265, 268, 286, 299

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-427589	Type II Na+/Pi cotransporters
R-HSA-5619097	Defective SLC34A3 causes Hereditary hypophosphatemic rickets with hypercalciuria (HHRH)

MSigDB gene sets: 193 (showing top): FREAC2_01, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, NFKB_C, GOBP_PHOSPHATE_ION_TRANSPORT, PPAR_DR1_Q2, GOCC_APICAL_PLASMA_MEMBRANE, MAF_Q6, FREAC4_01, FOXJ2_02, TGTYNNNNNRGCARM_UNKNOWN, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_SODIUM_ION_TRANSPORT, GOCC_CELL_PROJECTION_MEMBRANE

GO Biological Process (7): sodium ion transport (GO:0006814), phosphate ion transport (GO:0006817), intracellular phosphate ion homeostasis (GO:0030643), sodium-dependent phosphate transport (GO:0044341), monoatomic ion transport (GO:0006811), sodium ion transmembrane transport (GO:0035725), transmembrane transport (GO:0055085)

GO Molecular Function (3): sodium:phosphate symporter activity (GO:0005436), protein binding (GO:0005515), symporter activity (GO:0015293)

GO Cellular Component (6): plasma membrane (GO:0005886), brush border (GO:0005903), apical plasma membrane (GO:0016324), brush border membrane (GO:0031526), vesicle (GO:0031982), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Sodium-coupled phosphate cotransporters	1
SLC transporter disorders	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
apical part of cell	2
metal ion transport	1
inorganic anion transport	1
phosphate ion homeostasis	1
intracellular chemical homeostasis	1
phosphate ion transport	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
cellular process	1
phosphate transmembrane transporter activity	1
solute:sodium symporter activity	1
binding	1
secondary active transmembrane transporter activity	1
membrane	1
cell periphery	1
microvillus	1
cluster of actin-based cell projections	1
plasma membrane region	1
brush border	1
apical plasma membrane	1
cell projection membrane	1
membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3001 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC34A3	FGF23	Q9GZV9	946
SLC34A3	PHEX	P78562	942
SLC34A3	KL	Q9UEF7	885
SLC34A3	CLCN5	P51795	835
SLC34A3	ENPP1	P22413	813
SLC34A3	SLC20A2	Q08357	805
SLC34A3	PTH	P01270	766
SLC34A3	SLC17A1	Q14916	749
SLC34A3	CYP24A1	Q07973	721
SLC34A3	CYP27B1	O15528	719
SLC34A3	SLC20A1	Q8WUM9	671
SLC34A3	PDZK1	Q5T2W1	669
SLC34A3	GALNT3	Q14435	662
SLC34A3	EMP1	P54849	644
SLC34A3	NHERF1	O14745	600
SLC34A3	TRPV5	Q9NQA5	600

IntAct

15 interactions, top by confidence:

A	B	Type	Score
SLC34A3	CLRN1	psi-mi:“MI:0915”(physical association)	0.560
CLRN1	SLC34A3	psi-mi:“MI:0915”(physical association)	0.560
SLC34A3	TMEM234	psi-mi:“MI:0915”(physical association)	0.560
SLC34A3	GPX8	psi-mi:“MI:0915”(physical association)	0.560
SLC34A3	TMEM167B	psi-mi:“MI:0915”(physical association)	0.560
SNTA1	GNAT3	psi-mi:“MI:0914”(association)	0.350
SLC30A6	PSMD14	psi-mi:“MI:0914”(association)	0.350
SLC34A3	TMEM234	psi-mi:“MI:0915”(physical association)	0.000
SLC34A3	GPX8	psi-mi:“MI:0915”(physical association)	0.000
SLC34A3	TMEM167B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): SLC34A3 (Two-hybrid), SLC34A3 (Two-hybrid), SLC34A3 (Two-hybrid), TMEM167B (Two-hybrid), SLC34A3 (Negative Genetic), SLC34A3 (Affinity Capture-MS), SLC34A3 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2M425, A1L1J9, A1L504, A6NH21, A8WCG0, B0BNG2, F1RMN2, O43292, O75908, O76062, O77759, O88496, O88908, O89109, P38435, Q07175, Q0P4Y8, Q49LS0, Q5KR61, Q5RF50, Q5XK03, Q5ZKZ9, Q643R3, Q658P3, Q6MG14, Q6NVG1, Q767L9, Q7TN60, Q7TPN3, Q7TQM4, Q7ZWN0, Q8BKF1, Q8C3X8, Q8IUH8, Q8IZY2, Q8N130, Q8VC65, Q8WMV1, Q91YD1, Q9BU23

Diamond homologs: O95436, O97704, P54463, Q06495, Q06496, Q27960, Q28620, Q5REV9, Q60825, Q80SU6, Q8K4R8, Q8N130, Q9DBP0, Q9JJ09

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SLC34A3	“up-regulates quantity”	phosphate(3-)	relocalization
PTH1R	“down-regulates quantity”	SLC34A3

Disease & clinical

Clinical variants and AI predictions

ClinVar

866 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	34
Likely pathogenic	44
Uncertain significance	372
Likely benign	288
Benign	21

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1066820	NC_000009.11:g.(?140127661)(140130868_?)del	Pathogenic
1070104	NM_001177316.2(SLC34A3):c.1584_1585del (p.Ile529fs)	Pathogenic
1332756	NM_001177316.2(SLC34A3):c.1336-11_1336-1del	Pathogenic
1418539	NM_001177316.2(SLC34A3):c.734del (p.Pro245fs)	Pathogenic
1422510	NM_001177316.2(SLC34A3):c.1008_1009dup (p.Gly337fs)	Pathogenic
1426	NM_001177316.2(SLC34A3):c.908del (p.Pro303fs)	Pathogenic
1430	NM_001177316.2(SLC34A3):c.228del (p.Cys77fs)	Pathogenic
1435	NM_001177316.2(SLC34A3):c.1093+41_1094-15del	Pathogenic
1459125	NM_001177316.2(SLC34A3):c.145C>T (p.Gln49Ter)	Pathogenic
1459243	NM_001177316.2(SLC34A3):c.1168C>T (p.Gln390Ter)	Pathogenic
1478875	NM_001177316.2(SLC34A3):c.1093+68_1106del	Pathogenic
1686208	NM_001177316.2(SLC34A3):c.1217G>T (p.Gly406Val)	Pathogenic
1916375	NM_001177316.2(SLC34A3):c.734dup (p.Leu246fs)	Pathogenic
1977258	NM_001177316.2(SLC34A3):c.1467_1477dup (p.Leu493fs)	Pathogenic
2007889	NM_001177316.2(SLC34A3):c.1556del (p.Gly519fs)	Pathogenic
2028563	NM_001177316.2(SLC34A3):c.292C>T (p.Gln98Ter)	Pathogenic
2065818	NM_001177316.2(SLC34A3):c.1246del (p.Leu416fs)	Pathogenic
2735380	NM_001177316.2(SLC34A3):c.1369G>A (p.Gly457Ser)	Pathogenic
2812578	NM_001177316.2(SLC34A3):c.841C>T (p.Gln281Ter)	Pathogenic
3254619	NM_001177316.2(SLC34A3):c.1622G>A (p.Trp541Ter)	Pathogenic
3646260	NM_001177316.2(SLC34A3):c.926-2A>G	Pathogenic
4074275	NC_000009.11:g.(?140125385)(140131007_?)del	Pathogenic
423399	NM_001177316.2(SLC34A3):c.210del (p.Gly71fs)	Pathogenic
438692	NM_001177316.2(SLC34A3):c.1556dup (p.Pro520fs)	Pathogenic
444094	NM_001177316.2(SLC34A3):c.575C>G (p.Ser192Trp)	Pathogenic
444096	NM_001177316.2(SLC34A3):c.1639_1652del (p.Arg547fs)	Pathogenic
4526815	NM_001177316.2(SLC34A3):c.135G>A (p.Trp45Ter)	Pathogenic
4631284	NM_001177316.2(SLC34A3):c.1101del (p.Phe368fs)	Pathogenic
4707389	NM_001177316.2(SLC34A3):c.1116G>A (p.Trp372Ter)	Pathogenic
4710329	NM_001177316.2(SLC34A3):c.926-1G>A	Pathogenic

SpliceAI

2248 predictions. Top by Δscore:

Variant	Effect	Δscore
9:137232069:CA:C	acceptor_loss	1.0000
9:137232070:A:AG	acceptor_gain	1.0000
9:137232070:A:AT	acceptor_loss	1.0000
9:137232071:G:GG	acceptor_gain	1.0000
9:137232162:GT:G	donor_loss	1.0000
9:137232163:T:A	donor_loss	1.0000
9:137232574:GA:G	acceptor_gain	1.0000
9:137232670:G:GT	donor_gain	1.0000
9:137232699:GGGCA:G	donor_gain	1.0000
9:137232700:GGCA:G	donor_gain	1.0000
9:137232700:GGCAG:G	donor_gain	1.0000
9:137232701:GCA:G	donor_gain	1.0000
9:137232701:GCAG:G	donor_gain	1.0000
9:137232704:G:GG	donor_gain	1.0000
9:137232776:C:A	acceptor_gain	1.0000
9:137232781:TAG:T	acceptor_loss	1.0000
9:137232782:A:AG	acceptor_gain	1.0000
9:137232782:AGG:A	acceptor_loss	1.0000
9:137232783:G:GG	acceptor_gain	1.0000
9:137232918:GCTGC:G	donor_gain	1.0000
9:137232921:GC:G	donor_gain	1.0000
9:137232926:GC:G	donor_gain	1.0000
9:137232928:G:GG	donor_gain	1.0000
9:137233000:GCA:G	acceptor_gain	1.0000
9:137233002:A:AG	acceptor_gain	1.0000
9:137233003:G:GG	acceptor_gain	1.0000
9:137233033:ATCAT:A	acceptor_gain	1.0000
9:137233113:GAG:G	donor_gain	1.0000
9:137233198:T:TA	acceptor_gain	1.0000
9:137233200:C:CA	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000009986 (9:137234344 A>C,G), RS1000066054 (9:137230859 C>T), RS1000973210 (9:137227844 A>G), RS1001318627 (9:137228131 G>A,C), RS1001752150 (9:137229795 C>A,T), RS1001836526 (9:137236926 C>G,T), RS1001885743 (9:137236794 C>G), RS1002083372 (9:137233509 G>A,C), RS1002180536 (9:137232296 G>A,C), RS1002792932 (9:137230665 C>T), RS1002925978 (9:137235543 G>A), RS1003424591 (9:137228881 C>T), RS1004005263 (9:137230468 C>A), RS1004147869 (9:137229316 A>G,T), RS1004186564 (9:137232781 T>C)

Disease associations

OMIM: gene MIM:609826 | disease phenotypes: MIM:241530, MIM:613861, MIM:612286, MIM:621304

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary hypophosphatemic rickets with hypercalciuria	Definitive	Semidominant

Mondo (5): hereditary hypophosphatemic rickets with hypercalciuria (MONDO:0009431), kidney disorder (MONDO:0005240), retinitis pigmentosa 59 (MONDO:0013468), hypophosphatemic nephrolithiasis/osteoporosis 1 (MONDO:0012850), developmental and epileptic encephalopathy 119 (MONDO:1060177)

Orphanet (3): Hereditary hypophosphatemic rickets with hypercalciuria (Orphanet:157215), Retinitis pigmentosa (Orphanet:791), Dominant hypophosphatemia with nephrolithiasis or osteoporosis (Orphanet:244305)

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000117	Renal phosphate wasting
HP:0000124	Renal tubular dysfunction
HP:0000787	Nephrolithiasis
HP:0000886	Deformed rib cage
HP:0000893	Bulging of the costochondral junction
HP:0000897	Rachitic rosary
HP:0000920	Enlargement of the costochondral junction
HP:0000924	Abnormality of the skeletal system
HP:0001252	Hypotonia
HP:0001288	Gait disturbance
HP:0001324	Muscle weakness
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0002007	Frontal bossing
HP:0002148	Hypophosphatemia
HP:0002150	Hypercalciuria
HP:0002515	Waddling gait
HP:0002653	Bone pain
HP:0002663	Delayed epiphyseal ossification
HP:0002748	Rickets
HP:0002749	Osteomalacia
HP:0002752	Sparse bone trabeculae
HP:0002753	Thin bony cortex
HP:0002756	Pathologic fracture
HP:0002757	Recurrent fractures
HP:0002979	Bowing of the legs
HP:0002980	Femoral bowing
HP:0002982	Tibial bowing
HP:0003013	Bulging epiphyses

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
C562793	Hypophosphatemic Rickets with Hypercalciuria, Hereditary (supp.)
C567363	Nephrolithiasis-Osteoporosis, Hypophosphatemic, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295900 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC34 family of sodium phosphate co-transporters

ChEMBL bioactivities

1 potent at pChembl≥5 of 2 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.72	IC50	1900	nM	CHEMBL4159390

PubChem BioAssay actives

1 with measured affinity, of 12 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-chloro-2-[[3-(2,3-dihydroxypropylsulfanylmethyl)benzoyl]amino]-N-[(E)-(3-fluorophenyl)methylideneamino]benzamide	1354856: Inhibition of human NaPi2c expressed in HEK293 cells coexpressing tetracyclin assessed as reduction in uptake of 33P-radiolabeled Pi incubated for 20 to 30 mins prior to substrate addition	ic50	1.9000	uM

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	decreases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
sodium arsenite	decreases expression	1
picene	increases expression	1
Sunitinib	increases expression	1
Copper	affects cotreatment, decreases expression	1
Phosphates	affects cotreatment, affects transport	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases expression	1
Sodium	affects cotreatment, affects transport	1
2,4-Dichlorophenoxyacetic Acid	decreases expression	1
Cyclosporine	decreases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4149753	Binding	Inhibition of human NaPi2c expressed in HEK293 cells coexpressing tetracyclin assessed as reduction in uptake of 33P-radiolabeled Pi incubated for 20 to 30 mins prior to substrate addition	Discovery of Orally Bioavailable Selective Inhibitors of the Sodium-Phosphate Cotransporter NaPi2a (SLC34A1). — ACS Med Chem Lett

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00067990	PHASE4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	PHASE4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	PHASE4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	PHASE4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	PHASE4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	PHASE4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	PHASE4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	PHASE4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	PHASE4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	PHASE4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	PHASE4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	PHASE4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	PHASE4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	PHASE4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	PHASE4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
NCT01101698	PHASE4	UNKNOWN	Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
NCT01150201	PHASE4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01155141	PHASE4	COMPLETED	Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
NCT01228279	PHASE4	COMPLETED	Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
NCT01334333	PHASE4	COMPLETED	Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients
NCT01437943	PHASE4	TERMINATED	Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients
NCT01545479	PHASE4	COMPLETED	Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition
NCT01614431	PHASE4	COMPLETED	N Acetyl Cysteine for Cystinosis Patients
NCT01631149	PHASE4	COMPLETED	Effect of Deep BLock on Intraoperative Surgical Conditions
NCT01722513	PHASE4	UNKNOWN	Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy
NCT01985360	PHASE4	COMPLETED	ISCHEMIA-Chronic Kidney Disease Trial
NCT02311010	PHASE4	UNKNOWN	Practical Use of Advagraf de Novo After Kidney Transplantation According to Recipient Genetic Polymorphism
NCT02413073	PHASE4	COMPLETED	Whole Body Vibration in Kidney Disease
NCT02444013	PHASE4	UNKNOWN	Folic Acid for Prevention of Contrast Induced Nephropathy
NCT02663713	PHASE4	COMPLETED	A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor to Clopidogrel in Patients With Prior Myocardial Infarction
NCT02707809	PHASE4	COMPLETED	Effects of Dexmedetomidine on Microcirculation of Kidney Transplant Recipient
NCT02761577	PHASE4	COMPLETED	A Prospective Study on Incidence and Prevention of Contrast-induced Nephropathy in Croatia
NCT03029351	PHASE4	TERMINATED	GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes