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2.A.58.1.3
Renal Na+/phosphate electroneutral symporter, NPTIIc, NPT2a or NaPi-IIc; responsible for hypophosphatemic hypercalciuric nephrolithiasis associated with rickets (Stechman et al., 2007). Catalyzes 2Na+:1Pi symport (Ghezzi et al., 2009). Interacts functionally with CFTR (Bakouh et al., 2012). Also interacts with PDZ1 but not PDZ2 of NHERF1 (Mamonova et al. 2015).  Pathogenic variants in the SLC34A1 and SLC34A3 genes, encoding sodium-phosphate cotransporters 2a (NPT2a) and 2c (NPT2c), are linked to rare phosphate-wasting disorders. Brunkhorst et al.  (2024) explore the clinical presentations, biochemical profiles, and treatment outcomes of this condition (Brunkhorst et al. 2025).  Renal Pi transporters are regulated, may provide novel drug targets for prevention or treatment of hyperphosphatemia, and contribute to the genetic risk to develop kidney stones and CKD (Wagner et al. 2025).

Accession Number:Q8N130
Protein Name:NPTIIc
Length:599
Molecular Weight:63520.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:11
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate sodium(1+), phosphate(3-)

Cross database links:

RefSeq: NP_543153.1   
Entrez Gene ID: 142680   
Pfam: PF02690   
OMIM: 241530  phenotype
609826  gene
KEGG: hsa:142680    hsa:142680   

Gene Ontology

GO:0016324 C:apical plasma membrane
GO:0016021 C:integral to membrane
GO:0015321 F:sodium-dependent phosphate transmembrane tr...
GO:0005436 F:sodium:phosphate symporter activity
GO:0030643 P:cellular phosphate ion homeostasis
GO:0006817 P:phosphate transport
GO:0006814 P:sodium ion transport
GO:0031526 C:brush border membrane
GO:0031410 C:cytoplasmic vesicle
GO:0015321 F:sodium-dependent phosphate transmembrane transporter activity
GO:0032026 P:response to magnesium ion
GO:0031667 P:response to nutrient levels

References (10)

[1] “Growth-related renal type II Na/Pi cotransporter.”  Segawa H.et.al.   11880379
[2] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[3] “DNA sequence and analysis of human chromosome 9.”  Humphray S.J.et.al.   15164053
[4] “SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis.”  Bergwitz C.et.al.   16358214
[5] “Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3.”  Lorenz-Depiereux B.et.al.   16358215
[6] “Growth-related renal type II Na/Pi cotransporter.”  Segawa H.et.al.   11880379
[7] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[8] “DNA sequence and analysis of human chromosome 9.”  Humphray S.J.et.al.   15164053
[9] “SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis.”  Bergwitz C.et.al.   16358214
[10] “Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3.”  Lorenz-Depiereux B.et.al.   16358215

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence 
1:	MPSSLPGSQV PHPTLDAVDL VEKTLRNEGT SSSAPVLEEG DTDPWTLPQL KDTSQPWKEL 
61:	RVAGRLRRVA GSVLKACGLL GSLYFFICSL DVLSSAFQLL GSKVAGDIFK DNVVLSNPVA 
121:	GLVIGVLVTA LVQSSSTSSS IVVSMVAAKL LTVRVSVPII MGVNVGTSIT STLVSMAQSG 
181:	DRDEFQRAFS GSAVHGIFNW LTVLVLLPLE SATALLERLS ELALGAASLT PRAQAPDILK 
241:	VLTKPLTHLI VQLDSDMIMS SATGNATNSS LIKHWCGTTG QPTQENSSCG AFGPCTEKNS 
301:	TAPADRLPCR HLFAGTELTD LAVGCILLAG SLLVLCGCLV LIVKLLNSVL RGRVAQVVRT 
361:	VINADFPFPL GWLGGYLAVL AGAGLTFALQ SSSVFTAAVV PLMGVGVISL DRAYPLLLGS 
421:	NIGTTTTALL AALASPADRM LSALQVALIH FFFNLAGILL WYLVPALRLP IPLARHFGVV 
481:	TARYRWVAGV YLLLGFLLLP LAAFGLSLAG GMVLAAVGGP LVGLVLLVIL VTVLQRRRPA 
541:	WLPVRLRSWA WLPVWLHSLE PWDRLVTRCC PCNVCSPPKA TTKEAYCYEN PEILASQQL