SLC34A2

Summary

SLC34A2 (solute carrier family 34 member 2, HGNC:11020) is a protein-coding gene on chromosome 4p15.2, encoding Sodium-dependent phosphate transport protein 2B (O95436). Involved in actively transporting phosphate into cells via Na(+) cotransport.

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.

Source: NCBI Gene 10568 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pulmonary alveolar microlithiasis (Definitive, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 233 total — 11 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 50
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_006424

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11020
Approved symbol	SLC34A2
Name	solute carrier family 34 member 2
Location	4p15.2
Locus type	gene with protein product
Status	Approved
Aliases	NAPI-3B, NaPi-2b, NPTIIb, NaPi2b, NAPI-IIb
Ensembl gene	ENSG00000157765
Ensembl biotype	protein_coding
OMIM	604217
Entrez	10568

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 15 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000382051, ENST00000503434, ENST00000504570, ENST00000507530, ENST00000510033, ENST00000513204, ENST00000645788, ENST00000872278, ENST00000872279, ENST00000872280, ENST00000872281, ENST00000872282, ENST00000954976, ENST00000954977, ENST00000954978, ENST00000954979

RefSeq mRNA: 3 — MANE Select: NM_006424 NM_001177998, NM_001177999, NM_006424

CCDS: CCDS3435, CCDS54750

Canonical transcript exons

ENST00000382051 — 13 exons

Exon	Start	End
ENSE00001034812	25662498	25662612
ENSE00001122602	25674505	25674629
ENSE00001122608	25674296	25674412
ENSE00001122612	25673087	25673254
ENSE00001122618	25671601	25671721
ENSE00001122624	25670738	25670833
ENSE00001122629	25669647	25669842
ENSE00001122648	25664202	25664330
ENSE00001122651	25662705	25662842
ENSE00001405830	25655851	25655890
ENSE00001490778	25676135	25678748
ENSE00003484561	25666128	25666271
ENSE00003565801	25667880	25667991

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 99.57.

FANTOM5 (CAGE): breadth broad, TPM avg 7.9471 / max 2868.6293, expressed in 250 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47138	7.2830	200
47134	0.4310	62
47135	0.0625	20
47137	0.0408	14
47139	0.0367	12
47141	0.0257	10
47140	0.0249	7
47136	0.0241	5
47144	0.0183	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	99.57	gold quality
palpebral conjunctiva	UBERON:0001812	99.42	gold quality
upper lobe of lung	UBERON:0008948	98.19	gold quality
upper lobe of left lung	UBERON:0008952	98.08	gold quality
lung	UBERON:0002048	96.82	gold quality
bronchial epithelial cell	CL:0002328	96.02	gold quality
epithelium of bronchus	UBERON:0002031	95.02	gold quality
right lung	UBERON:0002167	94.76	gold quality
bronchus	UBERON:0002185	94.06	gold quality
right uterine tube	UBERON:0001302	92.77	gold quality
endometrium	UBERON:0001295	88.97	gold quality
minor salivary gland	UBERON:0001830	86.91	gold quality
right lobe of thyroid gland	UBERON:0001119	86.59	gold quality
decidua	UBERON:0002450	85.03	gold quality
islet of Langerhans	UBERON:0000006	84.55	gold quality
left lobe of thyroid gland	UBERON:0001120	83.78	gold quality
saliva-secreting gland	UBERON:0001044	83.05	gold quality
metanephros cortex	UBERON:0010533	81.73	gold quality
thyroid gland	UBERON:0002046	81.70	gold quality
adult organism	UBERON:0007023	81.66	gold quality
mouth mucosa	UBERON:0003729	81.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.88	gold quality
gall bladder	UBERON:0002110	78.33	gold quality
epithelium of nasopharynx	UBERON:0001951	76.88	gold quality
fallopian tube	UBERON:0003889	76.66	gold quality
pancreas	UBERON:0001264	76.46	gold quality
duodenum	UBERON:0002114	75.96	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	75.84	gold quality
visceral pleura	UBERON:0002401	75.53	gold quality
body of pancreas	UBERON:0001150	73.73	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	4380.93
E-MTAB-8530	yes	929.53
E-HCAD-1	yes	115.28
E-MTAB-10287	yes	44.57
E-GEOD-130148	yes	25.75
E-MTAB-6678	yes	8.63
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, NFIC, NR1I2

miRNA regulators (miRDB)

89 targeting SLC34A2, 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-6740-5P	100.00	65.64	932
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4699-3P	99.71	70.15	3142

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The current study was performed to characterize the minimal promoter region and transcriptional factor(s) necessary to activate gene expression of NaPi-IIb in human intestinal cells. (PMID:15458926)
• Study identified a pulmonary alveolar microlithiasis locus by homozygosity mapping to 4p15, then identified, by a candidate-gene approach, the gene responsible for the disease as SLC34A2, which is involved in phosphate homeostasis in several organs. (PMID:16960801)
• The performed study revealed that SLC34A2 gene exhibited the most distinct change in expression and may become a molecular marker of papillary thyroid cancer (PMID:17091453)
• Mutations in the SLC34A2 gene that abolish normal gene function cause pulmonary alveolar microlithiasis. (PMID:17095743)
• The monoclonal antibodies were shown to recognize specifically transiently overexpressed and endogenous NaPi2b in commonly used immunoassays. (PMID:18724815)
• SLC34A2 is associated with sodium-lithium countertransport activity and blood pressure (PMID:19119262)
• In human lung alveolar epithelial cells, the content of calcium and phosphate in cell supernatant decreased with increased amount of SLC34A2 mRNA. (PMID:19134407)
• The gene responsible for PAM, SLC34A2, has been identified. It encodes a type IIb sodium-dependent phosphate transporter, the function of which provides an insight into the pathogenesis of this disease. (PMID:19617834)
• A novel mutation in exon 8 of the SLC34A2 gene were associated with pulmonary alveolar microlithiasis in Chinese pedigree. (PMID:20017296)
• study describes mutations in SLC34A 2 gene in an inbred Turkish family with three siblings diagnosed with pulmonary alveolar microlithiasis(PAM); findings suggest that impaired activity of the SLC34A2 gene may be responsible for familial PAM (PMID:20046000)
• There was a significantly increased gene expression of SLC34A2 (normal tissues: 6.71+/-0.77; tumour tissues: 10.29+/-0.80) among breast cancer tissues compared with normal tissues. (PMID:21036732)
• Upregulation of SLC34A2 gene expression in well-differentiated tumors may reflect cell differentiation processes during ovarian cancerogenesis and could serve as potential marker for ovarian cancer diagnosis and prognosis. (PMID:21716206)
• study provides the data on the pattern of NaPi2b expression and cellular localization in breast, lung and ovarian cancers (PMID:21956469)
• identified 2 cases of pulmonary alveolar microlithiasis(PAM) with new mutations of SLC34A2 gene; identified the NaPi-IIb in a aortic valve; hypothesize that mutations in SLC34A2 may play a role in development of aortic valve calcification and arteriosclerosis (PMID:22336687)
• a comprehensive analysis indicates that SCL34A2 is the only gene of the several phosphate transporters genes whose expression differentiates normal from carcinoma samples, suggesting it might exert a major role in ovarian carcinomas. (PMID:22553815)
• investigation revealed that the c.910A > T mutation in the SCL34A2 gene was responsible for pulmonary alveolar microlithiasis (PAM) patients in China (PMID:23164546)
• Data indicate that humanized monoclonal antibody Rebmab200 and murine monoclonal antibody MX35 monoclonal antibodies had similar specificity for sodium phosphate transporter NaPi2b. (PMID:23936189)
• SLC34A2 might be associated with the initiation and progression of lung adenocarcinoma (PMID:25017204)
• our data indicated that SLC34A2 could exert significantly suppressive effects on tumorigenesis and progression of NSCLC. SLC34A2 might provide new insights for further understanding the early pathogenesis of human non-small cell lung cancer (PMID:26156586)
• SPAK and OSR1 are powerful stimulators of the intestinal Na+-coupled phosphate co-transporter NaPi-IIb (PMID:26506223)
• our work indicated that decreased SLC34A2 expression sensitized BCSCs to doxorubicin via SLC34A2-Bmi1-ABCC5 signaling and shed new light on understanding the mechanism of chemoresistance in BCSCs. This study not only bridges the missing link between stem cell-related transcription factor (Bmi1) and ABC transporter (ABCC5) but also contributes to development of potential therapeutics against breast cancer. (PMID:26546432)
• Our work sheds new light on the nature of the state of lung cancer stem cell-like cells and the role of SLC34A2 in the tumorigenicity of these cells (PMID:26846105)
• Low SLC34A2 expression is associated with non-small cell lung cancer. (PMID:26910912)
• SLC34A2 has an important role in promoting proliferation and tumorigenicity of BC. (PMID:28151475)
• Knockdown of SLC34A2 inhibits proliferation. (PMID:28281971)
• a novel role of SLC34A2 inbreast cancer stem cells (BCSCs) state regulation and establishes a rationale for targeting the SLC34A2/PI3K/AKT/SOX2 signaling pathway for breast cancer therapy. (PMID:28381172)
• Studied expression of solute carrier family 34 member 2 (SLC34A2/NaPi2b) in epithelial ovarian cancer using monoclonal antibody MX35 and immunohistochemistry. Different staining intensities were observed in different grades of epithelial ovarian cancer. (PMID:28464843)
• High expression of SLC34A2 was identified in about 2/3 patients and correlated with significantly better patient’s overall survival. Epidermal growth factor receptor mutations were detected in about 53% of patients with no statistically significant difference to patient’s overall survival. Anaplastic lymphoma kinase rearrangement was found in 8 out of 175 patients, harboring this abnormality leads to shorter overall survi (PMID:28720066)
• SLC34A2 was down-regulated in osteosarcoma patients.SLC34A2 interacted with PTEN, and decreased the phosphorylation of PI3K and AKT, which inactivated the PI3K/AKT signaling pathway. (PMID:28777670)
• SLC34A2 regulated sphere formation and self-renewal properties of CD44(+) gastric cancer stem cell-like cells (GCSCs), in vitro and in vivo. Mechanistic investigations revealed that Gsk3beta was the most strikingly up-regulated gene in response to SLC34A2 knockdown in GCSCs and Wnt/beta-cantenin signaling was required for SLC34A2-mediated sphere formation. (PMID:29178392)
• SLC34A2 plays a crucial promoting role in colorectal cancer development. (PMID:29653487)
• he SLC34A2-ROS-HIF-1-induced overexpression of EZH2 promotes colorectal cancer (CRC) cells proliferation and chemo-resistance to apoptosis. SLC34A2-ROS-HIF-1-EZH2 signaling pathway might serve as a novel therapeutic target against CRC. (PMID:30038060)
• The upstream breakpoint lies in the same region as the breakpoint of a fused gene SLC34A2-ROS1, which encodes a constitutive kinase in the lung cancer cell line HCC78 and nonsmall-cell lung cancer (NSCLC), suggesting that the deletion in this family is a hot spot for recombination, not only in cancer samples with somatic mutation, but also in PAM patients with germline genetic defects of SLC34A2. (PMID:30262706)
• Findings suggest that solute carrier 34 A2 (SLC34A2) might be a potential therapeutic target for the therapy of glioma patients. (PMID:30592329)
• The results demonstrate that miR-25/Gsk3beta-mediated activation of Wnt signaling is responsible for SLC34A2-induced enhancement of neuroblastoma cell stemness. (PMID:30868061)
• Phase Ia Study of Anti-NaPi2b Antibody-Drug Conjugate Lifastuzumab Vedotin DNIB0600A in Patients with Non-Small Cell Lung Cancer and Platinum-Resistant Ovarian Cancer. (PMID:31540980)
• Eight novel variants in the SLC34A2 gene in pulmonary alveolar microlithiasis. (PMID:31831582)
• SLC34A2 simultaneously promotes papillary thyroid carcinoma growth and invasion through distinct mechanisms. (PMID:32005974)
• Characterization of SLC34A2 as a Potential Prognostic Marker of Oncological Diseases. (PMID:34944522)
• Impaired phosphate transport in SLC34A2 variants in patients with pulmonary alveolar microlithiasis. (PMID:35443721)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Slc34a2	ENSMUSG00000029188
rattus_norvegicus	Slc34a2	ENSRNOG00000004626
caenorhabditis_elegans		WBGENE00022767

Paralogs (2): SLC34A1 (ENSG00000131183), SLC34A3 (ENSG00000198569)

Protein

Protein identifiers

Sodium-dependent phosphate transport protein 2B — O95436 (reviewed: O95436)

Alternative names: Na(+)-dependent phosphate cotransporter 2B, NaPi3b, Sodium/phosphate cotransporter 2B, Solute carrier family 34 member 2

All UniProt accessions (3): D6RA94, D6RBC0, O95436

UniProt curated annotations — full annotation on UniProt →

Function. Involved in actively transporting phosphate into cells via Na(+) cotransport.

Subcellular location. Apical cell membrane.

Tissue specificity. Highly expressed in lung. Also detected in pancreas, kidney, small intestine, ovary, testis, prostate and mammary gland. In lung, it is found in alveolar type II cells but not in bronchiolar epithelium.

Disease relevance. Pulmonary alveolar microlithiasis (PULAM) [MIM:265100] Rare disease characterized by the deposition of calcium phosphate microliths throughout the lungs. Most patients are asymptomatic for several years or even for decades and generally, the diagnosis is incidental to clinical investigations unrelated to the disease. Cases with early-onset or rapid progression are rare. A ‘sandstorm-appearing’ chest roentgenogram is a typical diagnostic finding. The onset of this potentially lethal disease varies from the neonatal period to old age and the disease follows a long-term, progressive course, resulting in a slow deterioration of lung functions. Pulmonary alveolar microlithiasis is a recessive monogenic disease with full penetrance. The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving SLC34A2 is found in a glioblastoma multiforme cell line U-118MG. Results in the formation of a SLC34A2-ROS1 chimeric protein that retains a constitutive kinase activity.

Induction. Down-regulated by EGF.

Similarity. Belongs to the SLC34A transporter family.

Isoforms (2)

UniProt ID	Names	Canonical?
O95436-1	1, NaPi-3b	yes
O95436-2	2, NaPi-2b, NaPi-IIb

RefSeq proteins (3): NP_001171469, NP_001171470, NP_006415* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003841	Na/Pi_transpt	Family

Pfam: PF02690

Catalyzed reactions (Rhea), 1 shown:

• 3 Na(+)(out) + phosphate(out) = 3 Na(+)(in) + phosphate(in) (RHEA:71255)

UniProt features (35 total): topological domain 9, transmembrane region 8, glycosylation site 5, sequence conflict 4, sequence variant 3, chain 1, region of interest 1, compositionally biased region 1, site 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95436-F1	73.27	0.24

Functional residue map

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

Catalytic / active sites (1): 126–127 (breakpoint for translocation to form a slc34a2-ros1 fusion protein)

Disulfide bonds (1): 303–350

Glycosylation sites (5): 295, 308, 313, 321, 340

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-427589	Type II Na+/Pi cotransporters
R-HSA-5619045	Defective SLC34A2 causes pulmonary alveolar microlithiasis (PALM)
R-HSA-5683826	Surfactant metabolism
R-HSA-5687583	Defective SLC34A2 causes PALM

MSigDB gene sets: 262 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, GOBP_PHOSPHATE_ION_TRANSPORT, GOBP_RESPONSE_TO_ESTROGEN, GOBP_RESPONSE_TO_HORMONE, YAMASHITA_METHYLATED_IN_PROSTATE_CANCER, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_EMBRYO_DEVELOPMENT, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_SODIUM_ION_TRANSPORT, TUOMISTO_TUMOR_SUPPRESSION_BY_COL13A1_UP

GO Biological Process (9): in utero embryonic development (GO:0001701), phosphate ion transport (GO:0006817), intracellular phosphate ion homeostasis (GO:0030643), response to estrogen (GO:0043627), sodium-dependent phosphate transport (GO:0044341), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), sodium ion transmembrane transport (GO:0035725), transmembrane transport (GO:0055085)

GO Molecular Function (5): sodium:phosphate symporter activity (GO:0005436), sodium ion binding (GO:0031402), phosphate ion binding (GO:0042301), protein binding (GO:0005515), symporter activity (GO:0015293)

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

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Sodium-coupled phosphate cotransporters	1
SLC transporter disorders	1
Metabolism of proteins	1
Diseases associated with surfactant metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
apical part of cell	2
chordate embryonic development	1
inorganic anion transport	1
phosphate ion homeostasis	1
intracellular chemical homeostasis	1
response to hormone	1
phosphate ion transport	1
metal 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
alkali metal ion binding	1
anion binding	1
binding	1
secondary active transmembrane transporter activity	1
membrane	1
cell periphery	1
microvillus	1
cluster of actin-based cell projections	1
cellular anatomical structure	1
plasma membrane region	1
brush border	1
apical plasma membrane	1
cell projection membrane	1
membrane-bounded organelle	1

Protein interactions and networks

STRING

3425 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC34A2	SLC17A1	Q14916	885
SLC34A2	ROS1	P08922	816
SLC34A2	RET	P07949	790
SLC34A2	GOPC	Q9HD26	768
SLC34A2	TPM3	P06753	747
SLC34A2	LRIG3	Q6UXM1	743
SLC34A2	SLC20A2	Q08357	738
SLC34A2	CD74	P04233	679
SLC34A2	KDELR2	P33947	656
SLC34A2	SDC4	P31431	650
SLC34A2	SLC20A1	Q8WUM9	647
SLC34A2	FGF23	Q9GZV9	624
SLC34A2	EML4	Q9HC35	624
SLC34A2	ALK	Q9UM73	586
SLC34A2	EZR	P15311	575

IntAct

8 interactions, top by confidence:

A	B	Type	Score
LINGO2	GAPDHS	psi-mi:“MI:0914”(association)	0.530
SLC34A2	LGALS8	psi-mi:“MI:0914”(association)	0.530
KRIT1	UBFD1	psi-mi:“MI:0914”(association)	0.350
SLC34A2	SYNGR2	psi-mi:“MI:0914”(association)	0.350
SLC34A2	SNAP23	psi-mi:“MI:0914”(association)	0.350
NUDCD1	FUOM	psi-mi:“MI:0914”(association)	0.350

BioGRID (150): PCDH10 (Affinity Capture-MS), SLC34A2 (Affinity Capture-MS), ENDOD1 (Affinity Capture-MS), ZDHHC18 (Affinity Capture-MS), LMTK2 (Affinity Capture-MS), SLC34A2 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), KIAA1715 (Affinity Capture-MS), ATP11C (Affinity Capture-MS), ATP6V0A2 (Affinity Capture-MS), SYNGR2 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), SLC30A7 (Affinity Capture-MS), SLC34A2 (Two-hybrid), SLC34A2 (Two-hybrid)

ESM2 similar proteins: A1A4I1, B0UYF2, O77750, O94300, O95436, O97596, P15710, P38361, P47863, P55088, Q08357, Q27960, Q28620, Q28677, Q28E01, Q2UVJ5, Q38954, Q5BL44, Q5I4F9, Q5R9L5, Q5REV9, Q5RK27, Q5XHF9, Q61609, Q63488, Q63632, Q63633, Q657W3, Q68F35, Q6NV12, Q6PB26, Q6PFM1, Q6Z0E2, Q7YRU6, Q80UP8, Q8WUM9, Q91V14, Q923J4, Q924N4, Q95L97

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

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SLC34A2	down-regulates	EGF
SLC34A2	“up-regulates quantity”	phosphate(3-)	relocalization

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — AML, COADREAD, LUAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	9
Uncertain significance	115
Likely benign	51
Benign	22

Top pathogenic / likely-pathogenic (20)

Variant ID	HGVS	Classification
1370306	NM_006424.3(SLC34A2):c.853C>T (p.Gln285Ter)	Pathogenic
208162	NM_006424.3(SLC34A2):c.212_224del (p.Asn71fs)	Pathogenic
2417674	NM_006424.3(SLC34A2):c.818del (p.Lys273fs)	Pathogenic
2971449	NM_006424.3(SLC34A2):c.1238G>A (p.Trp413Ter)	Pathogenic
3724784	NM_006424.3(SLC34A2):c.1056dup (p.Ile353fs)	Pathogenic
3764726	NM_006424.3(SLC34A2):c.910A>T (p.Lys304Ter)	Pathogenic
4766436	NM_006424.3(SLC34A2):c.843dup (p.Val282fs)	Pathogenic
5714	NC_000004.12:g.25655728_25655913del	Pathogenic
5715	NM_006424.3(SLC34A2):c.114del (p.Asp39fs)	Pathogenic
5716	NM_006424.3(SLC34A2):c.226C>T (p.Gln76Ter)	Pathogenic
687145	GRCh37/hg19 4p15.2(chr4:25668462-25681490)x1	Pathogenic
3065913	NM_006424.3(SLC34A2):c.1342_1361del (p.Val448fs)	Likely pathogenic
3362777	NM_006424.3(SLC34A2):c.927+1G>C	Likely pathogenic
4277473	NM_006424.3(SLC34A2):c.524-1G>C	Likely pathogenic
4277474	NM_006424.3(SLC34A2):c.1328del (p.Leu443fs)	Likely pathogenic
4293888	NM_006424.3(SLC34A2):c.1613_1616del (p.Phe537_Phe538insTer)	Likely pathogenic
4761349	NM_006424.3(SLC34A2):c.379+1G>A	Likely pathogenic
4768681	NM_006424.3(SLC34A2):c.1049-2A>T	Likely pathogenic
5717	NM_006424.3(SLC34A2):c.316G>C (p.Gly106Arg)	Likely pathogenic
981832	NM_006424.3(SLC34A2):c.113-2A>G	Likely pathogenic

SpliceAI

1067 predictions. Top by Δscore:

Variant	Effect	Δscore
4:25662496:A:AG	acceptor_gain	1.0000
4:25662497:G:GA	acceptor_gain	1.0000
4:25662497:GACC:G	acceptor_gain	1.0000
4:25662610:AAA:A	donor_gain	1.0000
4:25662610:AAAGT:A	donor_loss	1.0000
4:25662611:AA:A	donor_gain	1.0000
4:25662613:G:GG	donor_gain	1.0000
4:25662693:T:TA	acceptor_gain	1.0000
4:25662697:T:TA	acceptor_gain	1.0000
4:25662703:A:AG	acceptor_gain	1.0000
4:25662704:G:GT	acceptor_gain	1.0000
4:25662704:GC:G	acceptor_gain	1.0000
4:25662704:GCA:G	acceptor_gain	1.0000
4:25662704:GCAGA:G	acceptor_gain	1.0000
4:25662706:A:AG	acceptor_gain	1.0000
4:25662707:G:GG	acceptor_gain	1.0000
4:25662836:TGGTC:T	donor_gain	1.0000
4:25662841:AGGTA:A	donor_loss	1.0000
4:25662844:T:G	donor_loss	1.0000
4:25664185:A:AG	acceptor_gain	1.0000
4:25664186:T:G	acceptor_gain	1.0000
4:25664190:A:AG	acceptor_gain	1.0000
4:25664191:C:G	acceptor_gain	1.0000
4:25664199:CA:C	acceptor_loss	1.0000
4:25664199:CAGAG:C	acceptor_gain	1.0000
4:25664200:A:AG	acceptor_gain	1.0000
4:25664200:AG:A	acceptor_loss	1.0000
4:25664200:AGAGA:A	acceptor_gain	1.0000
4:25664201:G:GG	acceptor_gain	1.0000
4:25664201:GA:G	acceptor_gain	1.0000

AlphaMissense

4516 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:25666229:A:C	S161R	0.999
4:25666231:C:A	S161R	0.999
4:25666231:C:G	S161R	0.999
4:25667952:T:A	V199D	0.999
4:25674373:A:C	S432R	0.999
4:25674375:C:A	S432R	0.999
4:25674375:C:G	S432R	0.999
4:25674376:A:C	S433R	0.999
4:25674378:C:A	S433R	0.999
4:25674378:C:G	S433R	0.999
4:25674549:G:C	G460R	0.999
4:25674550:G:A	G460D	0.999
4:25674550:G:T	G460V	0.999
4:25674561:G:C	G464R	0.999
4:25674562:G:A	G464D	0.999
4:25666223:A:C	S159R	0.998
4:25666225:C:A	S159R	0.998
4:25666225:C:G	S159R	0.998
4:25667923:C:A	N189K	0.998
4:25667923:C:G	N189K	0.998
4:25674349:G:C	A424P	0.998
4:25674547:T:C	L459P	0.998
4:25674549:G:T	G460C	0.998
4:25674557:C:A	N462K	0.998
4:25674557:C:G	N462K	0.998
4:25667915:G:A	G187R	0.997
4:25667915:G:C	G187R	0.997
4:25669683:C:A	N224K	0.997
4:25669683:C:G	N224K	0.997
4:25674346:G:A	G423R	0.997

dbSNP variants (sampled 300 via entrez): RS1000003275 (4:25661269 G>A), RS1000253623 (4:25677883 T>A,C), RS1000282895 (4:25672578 T>C), RS1000390051 (4:25678046 T>C), RS1000480012 (4:25663714 A>G,T), RS1000510970 (4:25656720 G>T), RS1000542927 (4:25661541 C>A,T), RS1000646662 (4:25657019 C>G,T), RS1000702439 (4:25662341 G>T), RS1000710696 (4:25669475 A>C), RS1000818857 (4:25667665 A>G), RS1000964839 (4:25678233 TC>T), RS1001046402 (4:25667606 C>A,G), RS1001158711 (4:25663065 C>G,T), RS1001295288 (4:25654452 A>G)

Disease associations

OMIM: gene MIM:604217 | disease phenotypes: MIM:265100

GenCC curated gene-disease

Disease	Classification	Inheritance
pulmonary alveolar microlithiasis	Definitive	Autosomal recessive

Mondo (2): pulmonary alveolar microlithiasis (MONDO:0009928), hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (2): Pulmonary alveolar microlithiasis (Orphanet:60025), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

50 total (30 of 50 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000144	Decreased fertility
HP:0000790	Hematuria
HP:0000961	Cyanosis
HP:0001708	Right ventricular failure
HP:0001824	Weight loss
HP:0001945	Fever
HP:0002091	Restrictive ventilatory defect
HP:0002093	Respiratory insufficiency
HP:0002094	Dyspnea
HP:0002105	Hemoptysis
HP:0002107	Pneumothorax
HP:0002110	Bronchiectasis
HP:0002113	Pulmonary infiltrates
HP:0002206	Pulmonary fibrosis
HP:0002240	Hepatomegaly
HP:0002789	Tachypnea
HP:0002875	Exertional dyspnea
HP:0002878	Respiratory failure
HP:0003473	Fatigable weakness
HP:0003621	Juvenile onset
HP:0003677	Slowly progressive
HP:0004241	Stippled calcification in carpal bones
HP:0004363	Abnormal circulating calcium concentration
HP:0004382	Mitral valve calcification
HP:0004724	Calcium nephrolithiasis
HP:0004963	Calcification of the aorta
HP:0005317	Increased pulmonary vascular resistance
HP:0006514	Intraalveolar nodular calcifications
HP:0006520	Progressive pulmonary function impairment

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_1367	Metabolite levels	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010366	lysophosphatidylethanolamine 16:0 measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
C562405	Pulmonary Alveolar Microlithiasis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4295685 (SINGLE PROTEIN), CHEMBL4680045 (CHIMERIC PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 27,769 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3286830	LORLATINIB	4	3,598
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL4298138	REPOTRECTINIB	4	1,038
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL1230609	FORETINIB	2	3,096

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

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 15 [PMID: 35034442]	Inhibition	7.19	pIC50

ChEMBL bioactivities

82 potent at pChembl≥5 of 82 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.72	IC50	0.19	nM	LORLATINIB
9.72	IC50	0.19	nM	CHEMBL5712062
9.40	IC50	0.4	nM	LORLATINIB
9.10	IC50	0.8	nM	REPOTRECTINIB
8.96	IC50	1.1	nM	CHEMBL6165880
7.85	IC50	14	nM	CHEMBL5170356
7.82	IC50	15	nM	CHEMBL5182987
7.68	IC50	21	nM	CHEMBL5177872
7.64	IC50	23.1	nM	BRIGATINIB
7.62	IC50	24	nM	CHEMBL5175794
7.48	IC50	33	nM	CHEMBL5194399
7.44	IC50	36	nM	CHEMBL5204879
7.44	IC50	36	nM	CHEMBL5177122
7.42	IC50	38	nM	CHEMBL5192822
7.41	IC50	39	nM	CHEMBL5177313
7.40	IC50	40	nM	CHEMBL5189512
7.38	IC50	42	nM	CHEMBL5188308
7.37	IC50	43	nM	CHEMBL5188991
7.34	IC50	46	nM	CHEMBL5185161
7.32	IC50	48	nM	CHEMBL5195035
7.29	IC50	51	nM	CRIZOTINIB
7.21	IC50	61	nM	CHEMBL5173115
7.19	IC50	64	nM	CHEMBL5171732
7.15	IC50	71	nM	CHEMBL5206581
7.15	IC50	71	nM	CHEMBL5192917
7.11	IC50	78	nM	CHEMBL5175718
7.11	IC50	77	nM	CHEMBL5195729
7.10	IC50	80	nM	CHEMBL5180710
7.08	IC50	83	nM	CHEMBL5172873
7.06	IC50	87	nM	CHEMBL5197268
7.06	IC50	87	nM	CHEMBL5209124
7.00	IC50	99	nM	FORETINIB
6.99	IC50	103	nM	CHEMBL5172080
6.97	IC50	107	nM	CHEMBL5171218
6.93	IC50	118	nM	CHEMBL5185371
6.92	IC50	120	nM	CHEMBL5174202
6.85	IC50	141	nM	CHEMBL5171861
6.83	IC50	147	nM	CHEMBL5169660
6.82	IC50	150	nM	CHEMBL4159390
6.79	IC50	161	nM	CHEMBL5176827
6.79	IC50	162	nM	CHEMBL5197607
6.78	IC50	166	nM	CHEMBL5203825
6.77	IC50	170	nM	CHEMBL5192916
6.75	IC50	179	nM	CHEMBL5203134
6.72	IC50	192	nM	CHEMBL5182774
6.70	IC50	201	nM	CHEMBL5208718
6.69	IC50	205	nM	CHEMBL5178155
6.62	IC50	237	nM	CHEMBL5199046
6.60	IC50	249	nM	CHEMBL5203083
6.59	IC50	257	nM	CHEMBL5188295

PubChem BioAssay actives

85 with measured affinity, of 123 total; 50 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
(16R)-19-amino-13-fluoro-4,8,16-trimethyl-9-oxo-17-oxa-4,5,8,20-tetrazatetracyclo[16.3.1.02,6.010,15]docosa-1(22),2,5,11,13,18,20-heptaene-3-carbonitrile	2187728: Inhibition of SLC34A2-ROS1 fusion protein expressed in human HCC78 cells assessed as inhibition of phosphorylated ROS1 incubated for 1 hr by ELISA analysis	ic50	0.0002	uM
Lorlatinib	1680103: Inhibition of SLC34A2-ROS1 (unknown origin) expressed in human HCC78 cells assessed as reduction in cell viability	ic50	0.0002	uM
3-[2-[2-[2-[[3-[[6,6-dimethyl-3-[[4-[2-[4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]ethyl]phenyl]carbamoyl]-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenyl]methyl-methylamino]ethoxy]ethoxy]ethoxy]propanoic acid	1854595: Inhibition of human NaPi2b transfected in human KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.0140	uM
N’-[2-[[3-[[3-[1-[4-chloro-3-(trifluoromethyl)phenyl]pyrazole-4-carbonyl]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenyl]methyl-pentan-3-ylamino]ethyl]-N-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethyl]-N’-methylbutanediamide	1854595: Inhibition of human NaPi2b transfected in human KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.0150	uM
4-[ethyl-[3-[[2-[[4-[2-[4-(methylsulfamoylcarbamoyl)phenyl]ethyl]phenyl]carbamoyl]-6-piperidin-1-yl-3-pyridinyl]carbamoyl]phenyl]sulfonylamino]cyclohexane-1-carboxylic acid	1891006: Inhibition of human NaPi2b stably expressed in CHO-K1 cells assessed as reduction in H2[33P]O4 uptake incubated for 30 mins by liquid scintillation counting method	ic50	0.0210	uM
3-[2-[2-[2-[2-[2-[2-[2-[2-[[3-[[6,6-dimethyl-3-[[4-[2-[4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]ethyl]phenyl]carbamoyl]-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenyl]methylsulfanyl]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoic acid	1854595: Inhibition of human NaPi2b transfected in human KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.0240	uM
N-[(E)-[4-chloro-3-(trifluoromethyl)phenyl]methylideneamino]-2-[[3-[2-[2-[2-[(2R)-3-(diethylamino)-2-hydroxypropoxy]ethoxy]ethoxy]ethoxy]benzoyl]amino]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophene-3-carboxamide	1901082: Inhibition of human NaPi2b expressed in KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.0330	uM
4-[2-[[3-[[3-[1-(4-chlorophenyl)pyrazole-4-carbonyl]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenyl]methyl-pentan-3-ylamino]ethyl-methylamino]-4-oxobutanoic acid	1878284: Inhibition of human NaPi2b	ic50	0.0360	uM
4-[2-[4-[[3-[[3-[[2-[3-carboxypropanoyl(methyl)amino]ethyl-pentan-3-ylamino]methyl]benzoyl]amino]-6-piperidin-1-ylpyridine-2-carbonyl]amino]phenyl]ethyl]benzoic acid	1891006: Inhibition of human NaPi2b stably expressed in CHO-K1 cells assessed as reduction in H2[33P]O4 uptake incubated for 30 mins by liquid scintillation counting method	ic50	0.0360	uM
4-[2-[[3-[[3-[1-[4-chloro-3-(trifluoromethyl)phenyl]pyrazole-4-carbonyl]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenyl]methyl-pentan-3-ylamino]ethyl-methylamino]-4-oxobutanoic acid	1878284: Inhibition of human NaPi2b	ic50	0.0380	uM
4-[2-[[3-[[3-[1-[4-chloro-3-(trifluoromethyl)phenyl]pyrazole-4-carbonyl]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenyl]sulfonyl-pentan-3-ylamino]ethyl-methylamino]-4-oxobutanoic acid	1878284: Inhibition of human NaPi2b	ic50	0.0390	uM
N-[(E)-[4-chloro-3-(trifluoromethyl)phenyl]methylideneamino]-2-[[3-[2-[2-[2-(diethylamino)ethoxy]ethoxy]ethoxy]benzoyl]amino]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophene-3-carboxamide	1901082: Inhibition of human NaPi2b expressed in KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.0400	uM
4-[[3-[[3-[1-[4-chloro-3-(trifluoromethyl)phenyl]pyrazole-4-carbonyl]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenyl]sulfonyl-ethylamino]cyclohexane-1-carboxylic acid	1878284: Inhibition of human NaPi2b	ic50	0.0420	uM
2-[2-[2-[2-[2-[2-[2-[3-[[6,6-dimethyl-3-[[3-methyl-4-[2-[4-(1,3-oxazol-2-yl)phenyl]ethyl]phenyl]carbamoyl]-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]acetic acid	1854595: Inhibition of human NaPi2b transfected in human KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.0430	uM
4-[2-[[3-[[6,6-dimethyl-3-[1-[3-(trifluoromethyl)phenyl]pyrazole-4-carbonyl]-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenyl]methyl-pentan-3-ylamino]ethyl-methylamino]-4-oxobutanoic acid	1878284: Inhibition of human NaPi2b	ic50	0.0460	uM
N’-[2-[[3-[[3-[1-[4-chloro-3-(trifluoromethyl)phenyl]pyrazole-4-carbonyl]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenyl]methyl-pentan-3-ylamino]ethyl]-N-[1-[2-(dimethylamino)ethylamino]-2-methyl-1-oxopropan-2-yl]-N’-methylbutanediamide	1878284: Inhibition of human NaPi2b	ic50	0.0480	uM
Crizotinib	1680103: Inhibition of SLC34A2-ROS1 (unknown origin) expressed in human HCC78 cells assessed as reduction in cell viability	ic50	0.0510	uM
2-[2-[2-[2-[[3-[[6,6-dimethyl-3-[[4-[2-[4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]ethyl]phenyl]carbamoyl]-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenyl]methoxy]ethoxy]ethoxy]ethoxy]acetic acid	1854595: Inhibition of human NaPi2b transfected in human KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.0610	uM
2-[2-[2-[2-[2-[2-[2-[[3-[[3-[[(E)-[4-chloro-3-(trifluoromethyl)phenyl]methylideneamino]carbamoyl]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenyl]methoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl-(2-methoxyethyl)amino]acetic acid	1854595: Inhibition of human NaPi2b transfected in human KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.0640	uM
4-[3-[4-[[2-[[3-[[2-[3-carboxypropanoyl(methyl)amino]ethyl-pentan-3-ylamino]methyl]benzoyl]amino]-1H-indole-3-carbonyl]amino]phenyl]propyl]benzoic acid	1869040: Inhibition of human NaPi2b expressed in CHO-K1 cells assessed as reduction in [33P] uptake preincubated with compound for 30 mins followed by [33P]O4 addition and measured after 30 mins by TopCount liquid scintillation counting method	ic50	0.0710	uM
2-[2-[2-[2-[2-[2-[2-[3-[[3-[[4-[2-(4-methoxycarbonylphenyl)ethyl]-3-methylphenyl]carbamoyl]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]acetic acid	1854595: Inhibition of human NaPi2b transfected in human KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.0710	uM
4-[2-[4-[[3-[[3-[(4-carboxycyclohexyl)-ethylsulfamoyl]benzoyl]amino]-6-piperidin-1-ylpyridine-2-carbonyl]amino]phenyl]ethyl]benzoic acid	1891006: Inhibition of human NaPi2b stably expressed in CHO-K1 cells assessed as reduction in H2[33P]O4 uptake incubated for 30 mins by liquid scintillation counting method	ic50	0.0770	uM
4-[3-[4-[[2-[[3-[[2-[3-carboxypropanoyl(methyl)amino]ethyl-heptan-4-ylamino]methyl]benzoyl]amino]-1H-indole-3-carbonyl]amino]phenyl]propyl]benzoic acid;hydrochloride	1869040: Inhibition of human NaPi2b expressed in CHO-K1 cells assessed as reduction in [33P] uptake preincubated with compound for 30 mins followed by [33P]O4 addition and measured after 30 mins by TopCount liquid scintillation counting method	ic50	0.0780	uM
4-[2-[[3-[[3-[1-(4-chlorophenyl)pyrazole-4-carbonyl]-6-cyclopropyl-5,7-dihydro-4H-thieno[2,3-c]pyridin-2-yl]carbamoyl]phenyl]methyl-pentan-3-ylamino]ethyl-methylamino]-4-oxobutanoic acid	1878284: Inhibition of human NaPi2b	ic50	0.0800	uM
2-[[3-[2-[2-[2-[(2R)-3-[bis(2-hydroxyethyl)amino]-2-hydroxypropoxy]ethoxy]ethoxy]ethoxy]benzoyl]amino]-N-[(E)-[4-chloro-3-(trifluoromethyl)phenyl]methylideneamino]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophene-3-carboxamide	1901082: Inhibition of human NaPi2b expressed in KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.0830	uM
N-[2-[[3-[[3-[1-[4-chloro-3-(trifluoromethyl)phenyl]pyrazole-4-carbonyl]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenyl]methyl-pentan-3-ylamino]ethyl]-N,N’-dimethyl-N’-[(2S,3R,4S,5R)-2,3,4,5,6-pentahydroxyhexyl]butanediamide	1878284: Inhibition of human NaPi2b	ic50	0.0870	uM
N-[(E)-[4-chloro-3-(trifluoromethyl)phenyl]methylideneamino]-2-[[3-[(4-hydroxypiperidin-1-yl)methyl]benzoyl]amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide	1901082: Inhibition of human NaPi2b expressed in KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.0870	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	2187728: Inhibition of SLC34A2-ROS1 fusion protein expressed in human HCC78 cells assessed as inhibition of phosphorylated ROS1 incubated for 1 hr by ELISA analysis	ic50	0.0990	uM
3-[2-[2-[2-[3-[[3-[[(E)-[4-chloro-3-(trifluoromethyl)phenyl]methylideneamino]carbamoyl]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenoxy]ethoxy]ethoxy]ethoxy]propanoic acid	1901082: Inhibition of human NaPi2b expressed in KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.1000	uM
methyl 4-[2-[4-[[2-[[3-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]benzoyl]amino]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophene-3-carbonyl]amino]phenyl]ethyl]benzoate	1854595: Inhibition of human NaPi2b transfected in human KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.1000	uM
N-[(E)-[4-chloro-3-(trifluoromethyl)phenyl]methylideneamino]-2-[[3-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]benzoyl]amino]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophene-3-carboxamide	1901082: Inhibition of human NaPi2b expressed in KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.1000	uM
methyl 4-[2-[4-[[2-[[3-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxymethyl]benzoyl]amino]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophene-3-carbonyl]amino]-2-methylphenyl]ethyl]benzoate	1854595: Inhibition of human NaPi2b transfected in human KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.1000	uM
N-(4-benzylphenyl)-2-[[3-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxymethyl]benzoyl]amino]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophene-3-carboxamide	1854595: Inhibition of human NaPi2b transfected in human KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.1000	uM
N-(4-ethylphenyl)-2-[[3-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxymethyl]benzoyl]amino]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophene-3-carboxamide	1854595: Inhibition of human NaPi2b transfected in human KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.1000	uM
4-[2-[4-[[2-[[3-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]benzoyl]amino]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophene-3-carbonyl]amino]phenyl]ethyl]benzoic acid	1854595: Inhibition of human NaPi2b transfected in human KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.1000	uM
2-[2-[2-[2-[2-[2-[2-[[3-[[6,6-dimethyl-3-[[4-[2-[4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]ethyl]phenyl]carbamoyl]-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenyl]methoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]acetic acid	1854595: Inhibition of human NaPi2b transfected in human KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.1030	uM
4-[2-[4-[[3-[[3-[[2-[3-carboxypropanoyl(methyl)amino]ethyl-pentan-3-ylamino]methyl]benzoyl]amino]-6-methoxypyridine-2-carbonyl]amino]phenyl]ethyl]benzoic acid	1891006: Inhibition of human NaPi2b stably expressed in CHO-K1 cells assessed as reduction in H2[33P]O4 uptake incubated for 30 mins by liquid scintillation counting method	ic50	0.1070	uM
4-[2-[[3-[[3-[1-(4-chlorophenyl)pyrazole-4-carbonyl]-4,5,6,7-tetrahydro-1-benzothiophen-2-yl]carbamoyl]phenyl]methyl-pentan-3-ylamino]ethyl-methylamino]-4-oxobutanoic acid	1878284: Inhibition of human NaPi2b	ic50	0.1180	uM
4-(2-tert-butyl-4,5-dichlorophenyl)-3-[[5-(trifluoromethyl)-2-pyridinyl]sulfanyl]-1H-1,2,4-triazol-5-one	1854595: Inhibition of human NaPi2b transfected in human KJMGER8 cells assessed as reduction in H2[33P]O4 uptake incubated for 60 mins by TopCount scintillation counting method	ic50	0.1200	uM
4-[2-[4-[[3-[[3-[ethyl-[4-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethylcarbamoyl]cyclohexyl]sulfamoyl]benzoyl]amino]-6-piperidin-1-ylpyridine-2-carbonyl]amino]phenyl]ethyl]benzoic acid	1891006: Inhibition of human NaPi2b stably expressed in CHO-K1 cells assessed as reduction in H2[33P]O4 uptake incubated for 30 mins by liquid scintillation counting method	ic50	0.1410	uM
4-[2-[4-[[3-[[3-[ethyl-[4-(methylsulfamoylcarbamoyl)cyclohexyl]sulfamoyl]benzoyl]amino]-6-piperidin-1-ylpyridine-2-carbonyl]amino]phenyl]ethyl]benzoic acid	1891006: Inhibition of human NaPi2b stably expressed in CHO-K1 cells assessed as reduction in H2[33P]O4 uptake incubated for 30 mins by liquid scintillation counting method	ic50	0.1470	uM
5-chloro-2-[[3-(2,3-dihydroxypropylsulfanylmethyl)benzoyl]amino]-N-[(E)-(3-fluorophenyl)methylideneamino]benzamide	1354855: Inhibition of human NaPi2b 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	0.1500	uM
4-[2-[4-[[3-[[3-[[2-[3-carboxypropanoyl(methyl)amino]ethyl-pentan-3-ylamino]methyl]benzoyl]amino]-6-(dimethylamino)pyridine-2-carbonyl]amino]phenyl]ethyl]benzoic acid	1891006: Inhibition of human NaPi2b stably expressed in CHO-K1 cells assessed as reduction in H2[33P]O4 uptake incubated for 30 mins by liquid scintillation counting method	ic50	0.1610	uM
4-[4-[[3-[[3-[[2-[3-carboxypropanoyl(methyl)amino]ethyl-pentan-3-ylamino]methyl]benzoyl]amino]-6-piperidin-1-ylpyridine-2-carbonyl]amino]phenoxy]benzoic acid	1891006: Inhibition of human NaPi2b stably expressed in CHO-K1 cells assessed as reduction in H2[33P]O4 uptake incubated for 30 mins by liquid scintillation counting method	ic50	0.1620	uM
4-[3-[4-[[2-[[3-[[2-[[4-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethylamino]-4-oxobutanoyl]-methylamino]ethyl-pentan-3-ylamino]methyl]benzoyl]amino]-1H-indole-3-carbonyl]amino]phenyl]propyl]benzoic acid	1869040: Inhibition of human NaPi2b expressed in CHO-K1 cells assessed as reduction in [33P] uptake preincubated with compound for 30 mins followed by [33P]O4 addition and measured after 30 mins by TopCount liquid scintillation counting method	ic50	0.1660	uM
N-[3-[1-[4-chloro-3-(trifluoromethyl)phenyl]pyrazole-4-carbonyl]-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophen-2-yl]-3-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]benzamide	1878284: Inhibition of human NaPi2b	ic50	0.1700	uM
4-[2-[[3-[[3-(1-benzylpyrazole-4-carbonyl)-6,6-dimethyl-5,7-dihydro-4H-1-benzothiophen-2-yl]carbamoyl]phenyl]methyl-pentan-3-ylamino]ethyl-methylamino]-4-oxobutanoic acid	1878284: Inhibition of human NaPi2b	ic50	0.1790	uM
4-[methyl-[2-[[3-[[2-[[4-[2-[4-(methylsulfamoylcarbamoyl)phenyl]ethyl]phenyl]carbamoyl]-6-piperidin-1-yl-3-pyridinyl]carbamoyl]phenyl]methyl-pentan-3-ylamino]ethyl]amino]-4-oxobutanoic acid	1891006: Inhibition of human NaPi2b stably expressed in CHO-K1 cells assessed as reduction in H2[33P]O4 uptake incubated for 30 mins by liquid scintillation counting method	ic50	0.1920	uM
4-[2-[4-[[3-[[3-[[2-[3-carboxypropanoyl(methyl)amino]ethyl-pentan-3-ylamino]methyl]benzoyl]amino]-6-(2-methoxyethoxy)pyridine-2-carbonyl]amino]phenyl]ethyl]benzoic acid	1891006: Inhibition of human NaPi2b stably expressed in CHO-K1 cells assessed as reduction in H2[33P]O4 uptake incubated for 30 mins by liquid scintillation counting method	ic50	0.2010	uM
4-[2-[4-[[3-[[3-[[2-[3-carboxypropanoyl(methyl)amino]ethyl-pentan-3-ylamino]methyl]benzoyl]amino]-6-morpholin-4-ylpyridine-2-carbonyl]amino]phenyl]ethyl]benzoic acid	1891006: Inhibition of human NaPi2b stably expressed in CHO-K1 cells assessed as reduction in H2[33P]O4 uptake incubated for 30 mins by liquid scintillation counting method	ic50	0.2050	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, increases methylation	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Nickel	increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
terbufos	increases methylation	1
arsenic pentoxide	increases expression	1
prothioconazole	increases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	increases methylation	1
Arsenates	increases uptake	1
Arsenic	increases transport	1
Vehicle Emissions	increases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Calcitriol	increases expression	1
Fonofos	increases methylation	1
Formaldehyde	increases expression	1
Methotrexate	decreases expression	1
Parathion	increases methylation	1
Smoke	decreases expression, increases abundance	1
Tretinoin	affects expression	1
Triclosan	increases expression	1

ChEMBL screening assays

31 unique, capped per target: 30 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4149752	ADMET	Inhibition of human NaPi2b 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
CHEMBL4257143	Binding	Inhibition of human Nap2B isoform-A expressed in HEK293 cells assessed as reduction in sodium-dependent 33Pi uptake after 23 mins by TopCount liquid scintillation counting method	Nhe3-binding compounds and methods for inhibiting phosphate transport

Cellosaurus cell lines

14 cell lines: 10 cancer cell line, 2 factor-dependent cell line, 1 spontaneously immortalized cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_2061	HCC78	Cancer cell line	Male
CVCL_C8U9	YU-1082	Cancer cell line
CVCL_C8UA	YU-1083	Cancer cell line
CVCL_C8UB	YU-1085	Cancer cell line
CVCL_E6J2	HCC78 ROS1 p.L2026M	Cancer cell line	Male
CVCL_E6J3	HCC78 ROS1 p.G2032R	Cancer cell line	Male
CVCL_E6J4	HCC78 ROS1 p.S1986Y	Cancer cell line	Male
CVCL_E6RU	Genomeditech CHO-K1 H_SLC34A2	Spontaneously immortalized cell line	Female
CVCL_E6UX	Genomeditech HEK-293 H_SLC34A2	Transformed cell line	Female
CVCL_TN01	HAP1 SLC34A2 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome