Creative Biogene Creative Biogene
Inquiry
Pages
Products
  1. Home
  2. Search Results for "SLC34A2"

SLC34A2

Official Full Name
solute carrier family 34 member 2
Organism
Homo sapiens
GeneID
10568
Background
The protein encoded by this gene is a pH-sensitive sodium-dependent phosphate transporter. Phosphate uptake is increased at lower pH. Defects in this gene are a cause of pulmonary alveolar microlithiasis. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, May 2010]
Synonyms
PULAM; NPTIIb; NaPi2b; NAPI-3B; NAPI-IIb;
Bio Chemical Class
Phosphate:sodium symporter
Protein Sequence
MAPWPELGDAQPNPDKYLEGAAGQQPTAPDKSKETNKTDNTEAPVTKIELLPSYSTATLIDEPTEVDDPWNLPTLQDSGIKWSERDTKGKILCFFQGIGRLILLLGFLYFFVCSLDILSSAFQLVGGKMAGQFFSNSSIMSNPLLGLVIGVLVTVLVQSSSTSTSIVVSMVSSSLLTVRAAIPIIMGANIGTSITNTIVALMQVGDRSEFRRAFAGATVHDFFNWLSVLVLLPVEVATHYLEIITQLIVESFHFKNGEDAPDLLKVITKPFTKLIVQLDKKVISQIAMNDEKAKNKSLVKIWCKTFTNKTQINVTVPSTANCTSPSLCWTDGIQNWTMKNVTYKENIAKCQHIFVNFHLPDLAVGTILLILSLLVLCGCLIMIVKILGSVLKGQVATVIKKTINTDFPFPFAWLTGYLAILVGAGMTFIVQSSSVFTSALTPLIGIGVITIERAYPLTLGSNIGTTTTAILAALASPGNALRSSLQIALCHFFFNISGILLWYPIPFTRLPIRMAKGLGNISAKYRWFAVFYLIIFFFLIPLTVFGLSLAGWRVLVGVGVPVVFIIILVLCLRLLQSRCPRVLPKKLQNWNFLPLWMRSLKPWDAVVSKFTGCFQMRCCCCCRVCCRACCLLCDCPKCCRCSKCCEDLEEAQEGQDVPVKAPETFDNITISREAQGEVPASDSKTECTAL
Open
Disease
Lung cancer, Ovarian cancer
Approved Drug
0
Clinical Trial Drug
2 +
Discontinued Drug
0

Cat.No. Product Name Price
Cat.No. Product Name Price
Cat.No. Product Name Price
Cat.No. Product Name Tag Price
Cat.No. Product Name Price

Detailed Information

The SLC34A2 gene is located on the short arm of human chromosome 4 (4p15.2) and consists of 13 exons. It encodes type IIb sodium-dependent phosphate symporter (NaPi-IIb), a transmembrane protein of 690 amino acids. NaPi-IIb belongs to the solute carrier family 34 (SLC34), which also includes NaPi-IIa (SLC34A1) and NaPi-IIc (SLC34A3), together forming a transport system essential for maintaining phosphate balance in the body.

Structurally, NaPi-IIb contains two highly conserved inverted repeat domains linked by a large extracellular loop, with both the N-terminus and C-terminus oriented to the cytoplasmic side of the membrane. This topology creates a classic transport channel that uses the sodium gradient to drive phosphate uptake. The transport activity of NaPi-IIb is strongly pH-dependent, with higher efficiency at lower pH values, suggesting a special role under acidic microenvironments such as those found in tumors.

Figure 1. Predicted model of the secondary topology of the human NaPi-IIb protein.Figure 1. Predicted model of the secondary topology of the human NaPi-IIb protein. (Jönsson ÅLM, et al., 2022)

The SLC34A2 gene gives rise to three transcript variants through alternative splicing, encoding two functional isoforms of NaPi-IIb. These isoforms differ slightly in distribution and regulation. The gene was first cloned from cDNA libraries of lung and small intestine tissue in 1999. Expression profiling shows that SLC34A2 is most abundant in the lung, small intestine, kidney, mammary gland, and ovary. At the protein level, NaPi-IIb is localized to the apical membrane of type II alveolar epithelial cells, where it clears phosphate from alveolar fluid to prevent calcium phosphate precipitation. In intestinal epithelial cells, it is enriched in the brush border membrane, mediating dietary phosphate absorption. In mammary tissue, NaPi-IIb supports phosphate secretion into milk, helping to maintain the calcium–phosphate balance during lactation. This multi-organ expression underscores its central role in systemic phosphate homeostasis, with dysfunction likely to disrupt multiple physiological systems.

Physiological and Pathological Functions of NaPi-IIb

Under physiological conditions, NaPi-IIb–mediated phosphate uptake is fundamental to mineral metabolism. Phosphate is not only a structural component of bone but also essential for ATP production, signaling through phosphorylation, and nucleic acid synthesis. In the lung, NaPi-IIb prevents the formation of calcium phosphate deposits by efficiently removing phosphate from the alveolar surface. In the mammary gland, NaPi-IIb regulates the phosphate content of milk, ensuring a balanced calcium–phosphate ratio critical for neonatal skeletal development.

Experimental models suggest that loss of NaPi-IIb function in mammary epithelial cells impairs calcium–phosphate balance, correlating with inflammatory processes such as mastitis. Proteomic studies further show that NaPi-IIb interacts with a network of proteins linked to calcium–phosphate metabolism, and its dysregulation disrupts ion homeostasis, triggering pathological responses.

Loss-of-function mutations in SLC34A2 are the cause of pulmonary alveolar microlithiasis (PAM), a rare recessive disorder characterized by progressive deposition of calcium phosphate microliths in alveoli. In this setting, defective NaPi-IIb fails to clear phosphate from the alveolar lumen, leading to binding with calcium and formation of microliths. Although primarily pulmonary, PAM is often accompanied by extrapulmonary calcifications, including valvular lesions such as aortic valve calcification. This has led to investigations into the contribution of NaPi-IIb dysfunction to calcific aortic valve disease (CAVD), particularly in early-onset cases.

NaPi-IIb in Cancer Biology

The role of NaPi-IIb in tumors is complex and context-dependent. In non-small cell lung cancer, NaPi-IIb expression is significantly reduced compared with normal lung tissue, and downregulation is associated with enhanced invasiveness and stem-like properties of cancer cells. Mechanistic studies show that loss of NaPi-IIb impacts the JAK/STAT signaling pathway, promoting malignant progression.

Conversely, in epithelial ovarian cancer, NaPi-IIb is frequently overexpressed, especially in high-grade serous carcinoma, making it an attractive therapeutic target. In addition, SLC34A2 gene rearrangements that create SLC34A2–ROS1 fusion proteins drive oncogenic signaling in certain tumors. These tissue-specific expression patterns highlight the heterogeneity of NaPi-IIb biology and provide a basis for selective therapeutic design.

Clinical and Translational Relevance

The tissue-selective expression of NaPi-IIb has been leveraged in drug development. Antibody–drug conjugates (ADCs) targeting NaPi-IIb are under clinical evaluation. Upifitamab rilsodotin (UpRi), developed using the Dolaflexin platform, is the first NaPi-IIb–directed ADC, designed to deliver a high drug payload with controlled bystander effects. Early clinical trials in NaPi-IIb–positive ovarian cancer have shown encouraging efficacy and tolerability, supporting its continued development.

NaPi-IIb also has value as a diagnostic and predictive marker. Genetic screening of SLC34A2 in families with PAM allows identification of carriers and early detection of disease. In calcific aortic valve disease, SLC34A2 variants may indicate susceptibility, particularly in younger patients. Furthermore, altered NaPi-IIb expression has been investigated as a biomarker in breast pathology and inflammation.

Challenges and Future Directions

Despite progress, significant challenges remain in translating NaPi-IIb biology into therapies. A key issue is minimizing off-target effects, as NaPi-IIb is physiologically expressed in several normal tissues. Strategies such as conditionally activated prodrugs or targeted delivery systems may improve specificity. Another challenge is fully elucidating the mechanisms by which NaPi-IIb deficiency contributes to systemic and multi-organ calcification. Therapeutic approaches such as phosphate chelators or transporter agonists are being explored as potential interventions.

Future research will continue to dissect the dual roles of NaPi-IIb in health and disease, advancing its potential both as a therapeutic target and as a biomarker in clinical practice.

Reference

  1. Lederer E, Wagner CA. Clinical aspects of the phosphate transporters NaPi-IIa and NaPi-IIb: mutations and disease associations. Pflugers Arch. 2019 Jan;471(1):137-148.

  2. Fenollar-Ferrer C, Forrest LR. Structural models of the NaPi-II sodium-phosphate cotransporters. Pflugers Arch. 2019 Jan;471(1):43-52.

  3. Jönsson ÅLM, Hernando N, Knöpfel T, et al. Impaired phosphate transport in SLC34A2 variants in patients with pulmonary alveolar microlithiasis. Hum Genomics. 2022 Apr 20;16(1):13.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry

Products

Transfected Stable Cell Lines

Premade Virus Particles

Laboratory Equipment

RNA Interference Products

Cell Lysate

Clones

Enzymes

Kits

Aptamers

Services

Stable Cell Line Generation

Target-based Drug Discovery Service

Custom Libraries Construction Service

Microbe Genome Editing Service

Biosafety Testing Service

Nucleotides Service

MicroRNA Service

RNAi Service

Custom Viral Service

Platforms

CRISPR/Cas9 PlatformCB

QvirusTM Platform

IntegrateRNA Platform

Microbiology Platform

Zebrafish Platform

Get in Touch

Tel

Fax

Email

USA

Germany

Copyright © Creative Biogene. All rights reserved.

Privacy Policy | Cookie Policy